48 results on '"Albright hereditary osteodystrophy"'
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2. Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients
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Serap Turan, Eileen M. Shore, Murat Bastepe, Olaf Hiort, Agnès Linglart, Francesca Elli, Roberto Bufo, Guiomar Perez de Nanclares, Michael A. Levine, Beatriz Lecumberri, M. Carola Zillikens, Rebeca Rodado, Vrinda Saraff, Ashley H. Shoemaker, Luisa De Sanctis, Guillemette Devernois, Gianpaolo De Filippo, Aurora Garcia Ramirez, Philip Murray, Susanne Thiele, Outi Mäkitie, Lars Rejnmark, Regina Matsunaga Martin, Manasori Minagawa, Timothee Choplin, Emily L. Germain-Lee, Giovanna Mantovani, Peter Kamenický, Harald Jüppner, Lionel Groussin, Nina Knight, Elvire Le Norcy, Anya Rothenbuhler, Neveen A. T. Hamdy, Robert J. Pignolo, David Monk, Thomas Eggermann, Caroline Silve, Arrate Pereda, Gabriel Á. Martos-Moreno, S Faisal Ahmed, Philip Woods, Patrick Hanna, Erasmus MC other, Internal Medicine, Mantovani, Giovanna, Bastepe, Murat, Monk, David, De Sanctis, Luisa, Thiele, Susanne, Ahmed, S. Faisal, Bufo, Roberto, Choplin, Timothee, De Filippo, Gianpaolo, Devernois, Guillemette, Eggermann, Thomas, Elli, Francesca M., Garcia Ramirez, Aurora, Germain-Lee, Emily L., Groussin, Lionel, Hamdy, Neveen A. T., Hanna, Patrick, Hiort, Olaf, Jueppner, Harald, Kamenicky, Peter, Knight, Nina, Le Norcy, Elvire, Lecumberri, Beatriz, Levine, Michael A., Maekitie, Outi, Martin, Regina, Martos-Moreno, Gabriel Angel, Minagawa, Manasori, Murray, Philip, Pereda, Arrate, Pignolo, Robert, Rejnmark, Lars, Rodado, Rebeca, Rothenbuhler, Anya, Saraff, Vrinda, Shoemaker, Ashley H., Shore, Eileen M., Silve, Caroline, Turan, Serap, Woods, Philip, Zillikens, M. Carola, Perez de Nanclares, Guiomar, Linglart, Agnes, HUS Children and Adolescents, Clinicum, Lastentautien yksikkö, Children's Hospital, University of Helsinki, and Helsinki University Hospital Area
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Pediatrics ,Endocrinology, Diabetes and Metabolism ,Acrodysostosis ,Psychological intervention ,Type 2 diabetes ,Ossification ,Parathyroid hormone ,STIMULATORY G-PROTEIN ,0302 clinical medicine ,Endocrinology ,3123 Gynaecology and paediatrics ,Diagnosis ,SKELETAL RESPONSIVENESS ,Medicine ,Child ,Subclinical infection ,030219 obstetrics & reproductive medicine ,Brachydactyly ,Calcium and phosphate metabolism ,Management ,3. Good health ,IDENTIFIES PDE4D MUTATIONS ,Pseudohypoparathyroidism ,Practice Guidelines as Topic ,INCREASED PREVALENCE ,medicine.symptom ,Bone disorders ,Consensus ,Treatment ,Adult ,Transition to Adult Care ,medicine.medical_specialty ,Genetic counseling ,PARATHYROID-HORMONE ,PROGRESSIVE OSSEOUS HETEROPLASIA ,030209 endocrinology & metabolism ,HORMONE-RELEASING-HORMONE ,Short stature ,Article ,03 medical and health sciences ,PSEUDO-PSEUDOHYPOPARATHYROIDISM ,Hypothyroidism ,Humans ,Dwarfism, Pituitary ,ALBRIGHT HEREDITARY OSTEODYSTROPHY ,business.industry ,ENERGY-EXPENDITURE ,medicine.disease ,Diabetes Mellitus, Type 2 ,Pediatrics, Perinatology and Child Health ,business - Abstract
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.
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- 2020
3. Calcitriol and Levothyroxine Dosing for Patients With Pseudohypoparathyroidism
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Jacqueline Antoun, Ashley H. Shoemaker, Merla Hubler, and Dylan Williamson
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calcitriol ,medicine.medical_specialty ,Calcitriol ,business.industry ,Brief Report ,Endocrinology, Diabetes and Metabolism ,levothyroxine ,Significant difference ,pseudohypoparathyroidism ,Levothyroxine ,Parathyroid hormone ,medicine.disease ,TSH resistance ,Endocrinology ,Thyroid-stimulating hormone ,Internal medicine ,medicine ,Dosing ,Albright hereditary osteodystrophy ,business ,PTH resistance ,AcademicSubjects/MED00250 ,Pseudohypoparathyroidism ,medicine.drug ,Hormone - Abstract
Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in GNAS. This cross-sectional study investigated whether PHP patients with parathyroid hormone (PTH), thyrotropin (thyroid stimulating hormone; TSH), and free thyroxine (T4) levels at goal required higher doses of levothyroxine and calcitriol than recommended by current guidelines to overcome mineral ion abnormalities due to hormone resistance. Baseline demographic and clinical data of participants enrolled in PHP research studies between 2012-2021 were collected via retrospective chart review. Longitudinally, data were recorded at a maximum frequency of once a year starting at 1 year of age. The PTH at goal (PAG) group was defined as PTH The PAG group (n = 74) was prescribed higher calcitriol doses than the PTH not at goal (PNAG) group (n = 50) (0.9 ± 1.1 vs 0.5 ± 0.9 mcg/day, P = 0.04) and 21% of individual patients were prescribed ≥ 1.5 mcg of calcitriol daily. This remained true after normalization for body weight (0.013 ± 0.015 vs 0.0067 ± 0.0095 mcg/kg/day, P = 0.008). There was no statistically significant difference in levothyroxine dosing between the TAG group (n = 122) and TSH and free T4 not at goal (TNAG) group (n = 45) when normalized for weight (2.0 ± 0.7 vs 1.8 ± 0.7 mcg/kg/day, P = 0.2). More than one-third of patients with PHP had PTH levels not at goal and some patients required calcitriol doses ≥ 1.5 mcg/day to meet current treatment goals.
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- 2021
4. Management of pseudohypoparathyroidism
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Emily L. Germain-Lee
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Adult ,Male ,Statement (logic) ,GTP-Binding Protein alpha Subunits ,MEDLINE ,Bioinformatics ,GNAS ,Mice ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,medicine ,Animals ,Humans ,Obesity ,Albright hereditary osteodystrophy ,Child ,Pseudohypoparathyroidism ,business.industry ,Extramural ,pseudohypoparathyroidism ,Infant ,medicine.disease ,ENDOCRINOLOGY AND METABOLISM: Edited by Sally Radovick ,3. Good health ,Child, Preschool ,Growth Hormone ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Pseudopseudohypoparathyroidism ,Female ,business - Abstract
Purpose of review This review is timely given the 2018 publication of the first international Consensus Statement for the diagnosis and management of pseudohypoparathyroidism (PHP) and related disorders. The purpose of this review is to provide the knowledge needed to recognize and manage PHP1A, pseudopseudohypoparathyroidism (PPHP) and PHP1B – the most common of the subtypes – with an overview of the entire spectrum and to provide a concise summary of management for clinical use. This review will draw from recent literature as well as personal experience in evaluating hundreds of children and adults with PHP. Recent findings Progress is continually being made in understanding the mechanisms underlying the PHP spectrum. Every year, through clinical and laboratory studies, the phenotypes are elucidated in more detail, as are clinical issues such as short stature, brachydactyly, subcutaneous ossifications, cognitive/behavioural impairments, obesity and metabolic disturbances. Headed by a European PHP consortium, experts worldwide published the first international Consensus that provides detailed guidance in a systematic manner and will lead to exponential progress in understanding and managing these disorders. Summary As more knowledge is gained from clinical and laboratory investigations, the mechanisms underlying the abnormalities associated with PHP are being uncovered as are improvements in management.
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- 2019
5. Subcutaneous Calcification and Fixed Flexion Deformity of the Right Elbow Joint in a Child with a GNAS Mutation: A Case Report
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Senthil Senniappan, Hussain Alsaffar, and Najya Attia
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musculoskeletal diseases ,medicine.medical_specialty ,Subcutaneous calcification ,Endocrinology, Diabetes and Metabolism ,Elbow ,Case Report ,Metacarpal bones ,Palpation ,03 medical and health sciences ,0302 clinical medicine ,Deformity ,medicine ,GNAS complex locus ,Obesity ,Pseudohypoparathyroidism ,030222 orthopedics ,biology ,medicine.diagnostic_test ,business.industry ,Albright Hereditary Osteodystrophy ,medicine.disease ,Surgery ,medicine.anatomical_structure ,biology.protein ,Calcium ,medicine.symptom ,business ,Complication - Abstract
Introduction: The art of medicine glorifies when a clinician listens carefully to the patient’s story, gives a thorough examination, performs appropriate investigations, and finally links findings together to reach a definite diagnosis. An interesting case was reported here, highlighting the integration of different symptoms and manifestations with some relevant biochemical investigations to reach a final diagnosis. To the best of our knowledge, fixed flexion deformity, as a complication of subcutaneous calcification, has not been previously reported in a child with Albright hereditary osteodystrophy (AHO). Case Presentation: A 2.5-year-old boy was born at term with a birth weight of 3.5 kg (-0.49 SDS). The child was referred to a general pediatrician with a history of right elbow joint swelling noticed initially at six months of age. He then developed the limitation of right upper arm movement, which slowly progressed afterward. The patient had no history of trauma. At nine months of age, he was diagnosed with hypothyroidism, preceded by cold skin, dry hair, and constipation. At nine years of age, he presented with a fixed flexion deformity of the right elbow associated with markedly limited joint movement and symmetrical hands with hyperpigmented knuckles of right metacarpal bones. Subcutaneous masses were felt along the right forearm, showing tenderness on palpation. Investigations revealed elevated serum parathyroid hormone and normal calcium indicating parathyroid hormone resistance. Further genetic testing revealed GNAS mutation. The child was obese throughout his childhood. Conclusions: This case report describes an obese child with subcutaneous calcification that led to fixed flexion deformity of the elbow, starting at an incredibly early age. Hypothyroidism and pseudohypoparathyroidism raised the suspicion of AHO, which was later confirmed by genetic testing. This is the first case report on fixed flexion deformity in a patient with GNAS mutation (c.719-1G > A Chr20: 57484737) in West Asia.
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- 2021
6. Pseudohypoparathyroidism in a child
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D. A. Kvacheniuk, T. M. Malynovska, I. V. Lukashuk, O. V. Bolshova, and N. A. Sprynchuk
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Calcium metabolism ,Hyperparathyroidism ,Pathology ,medicine.medical_specialty ,business.industry ,Osteoporosis ,Parathyroid hormone ,medicine.disease ,Urinary calcium ,Phosphorus metabolism ,Hypoparathyroidism ,дети ,псевдогипопаратиреоз ,наследственная остеодистрофия Олбрайта ,ожирение ,гипокальциемия ,резистентность к паратиреоидному гормону ,medicine ,children ,pseudohypoparathyroidism ,Albright hereditary osteodystrophy ,obesity ,hypocalcemia ,parathyroid hormone resistance ,псевдогіпопаратиреоз ,спадкова остеодистрофія Олбрайта ,ожиріння ,гіпокальціємія ,резистентність до паратиреоїдного гормону ,business ,Pseudohypoparathyroidism - Abstract
Pseudohypoparathyroidism (Albright hereditary osteodystrophy) is a rare inherited disease of the skeletal system caused by impaired calcium and phosphorus metabolism that mimics hypoparathyroidism. It is often accompanied by mental and physical retardation. The disease is characterized by a pronounced clinical polymorphism, which is based on genetic heterogeneity. In the bone tissue there are changes typical of hyperparathyroidism: diffuse osteoporosis, the appearance of cysts (so-called brown tumors, giant cell tumors). Calcium, which is released from the bones, is deposited as calcifications in the subcutaneous tissue, as well as in the kidneys, muscles, myocardium, the walls of the large arteries, eye conjunctiva and periphery of the cornea. The cause of pseudohypoparathyroidism is a congenital defect — a genetically determined kidneys and skeleton resistance to parathyroid hormone. A diagnostic algorithm for monitoring of patients with pseudohypoparathyroidism is presented. In the presence of clinical symptoms that give reason to suspect pseudohypoparathyroidism, it is advisable to determine total and ionized calcium and phosphorus in the blood, urinary calcium excretion, as well as blood level of parathyroid hormone. Elevated blood parathyroid hormone and phosphorus along with low calcium in the blood and urine allow the diagnosis to be made. Timely diagnosis and clarification of the genesis of each syndrome are important for optimizing the treatment of these conditions and prevention of possible complications, as well as for determining the need for genetic counseling., Псевдогипопаратиреоз (наследственная остеодистрофия Олбрайта, болезнь Олбрайта) — редкое наследственное заболевание костной системы, вызванное нарушением обмена кальция и фосфора, имитирующее гипопаратиреоз. Часто сопровождается задержкой умственного и физического развития.Патология характеризуется выраженным клиническим полиморфизмом, в основе которого лежит генетическая гетерогенность.В костной ткани отмечают изменения, типичные для гиперпаратиреоза — диффузный остеопороз, появление кист (так называемые бурые опухоли, гигантоклеточные опухоли). Высвобождающийся из костей кальций откладывается в виде кальцинатов в подкожной клетчатке, а также в почках, мышцах, миокарде, стенках крупных артерий, конъюнктиве глаза и по периферии роговицы.Причиной возникновения псевдогипопаратиреоза является врожденный дефект — генетически обусловленная резистентность почек и скелета к действию паратгормона.Приведен диагностический алгоритм мониторинга больных с псевдогипопаратиреозом. При наличии клинических симптомов, позволяющих заподозрить псевдогипопаратиреоз, целесообразно определить содержание общего и ионизированного кальция и фосфора в крови, экскрецию кальция с мочой, а также уровень паратгормона в крови. Повышенный уровень паратгормона и фосфора в крови при низком содержании кальция в крови и моче позволяют поставить диагноз. Своевременная диагностика и уточнение генеза каждого синдрома имеют важное значение для оптимизации лечения этих состояний и профилактики возможных осложнений, а также целесообразности медико-генетического консультирования., Псевдогіпопаратиреоз (спадкова остеодистрофія Олбрайта, хвороба Олбрайта) — рідкісне спадкове захворювання кісткової системи, спричинене порушенням обміну кальцію і фосфору, яке імітує гіпопаратиреоз. Часто супроводжується затримкою розумового та фізичного розвитку. Патологія характеризується вираженим клінічним поліморфізмом, в основі якого лежить генетична гетерогенність. У кістковій тканині відзначають зміни, типові для гіперпаратиреозу, — дифузний остеопороз, появу кіст (так звані бурі пухлини, гігантськоклітинні пухлини). Кальцій, який вивільняється з кісток, відкладається у вигляді кальцинатів у підшкірній клітковині, а також у нирках, м’язах, міокарді, стінках великих артерій, кон’юнктиві ока і по периферії рогівки. Причиною виникнення псевдогіпопаратиреозу є природжений дефект — генетично зумовлена резистентність нирок і скелета до дії паратгормону. Наведено діагностичний алгоритм моніторингу хворих із псевдогіпопаратиреозом. За наявності клінічних симптомів, які дають підставу запідозрити псевдогіпопаратиреоз, доцільно визначити вміст загального та йонізованого кальцію і фосфору в крові, екскрецію кальцію із сечею, а також рівень паратгормону в крові. Підвищений рівень паратгормону і фосфору в крові за низького вмісту кальцію в крові та сечі дають змогу встановити діагноз. Своєчасна діагностика та уточнення генезу кожного синдрому мають важливе значення для оптимізації лікування цих станів і профілактики можливих ускладнень, а також доцільності медико-генетичного консультування.
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- 2020
7. Case report: An infantile lethal form of Albright hereditary osteodystrophy due to a GNAS mutation
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Valérie Leclercq, Isabelle Maystadt, Catherine Wanty, Olivier Robaux, Damien Lederer, Valérie Benoit, Mélanie Delaunoy, Marcela Ruiz, and Claire de Halleux
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musculoskeletal diseases ,0301 basic medicine ,inactivating PTH/PTHrP signaling disorders ,Case Report ,Case Reports ,030105 genetics & heredity ,medicine.disease_cause ,Germline ,Albright hereditary osteodystrophy ,03 medical and health sciences ,GNAS complex locus ,Medicine ,GNAS mutation ,Osteodystrophy ,Albright's hereditary osteodystrophy ,Pseudohypoparathyroidism ,Genetics ,Mutation ,severe phenotype ,biology ,business.industry ,pseudohypoparathyroidism ,General Medicine ,medicine.disease ,Phenotype ,biology.protein ,business - Abstract
Key Clinical Message Germline loss‐of‐function GNAS mutations are associated with multiple phenotypes, depending on the parental origin of the mutant allele. Here, we describe an infantile lethal form of atypical pseudohypoparathyroidism type 1a or 1c with severe Albright's hereditary osteodystrophy phenotype, underlying the extremely variable expressivity of this syndrome.
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- 2018
8. Albright hereditary osteodystrophy: dental management case report
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Berenice Barbachan e Silva, Jonas de Almeida Rodrigues, and Stephanie Anagnostopoulos Friedrich
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Pediatrics ,medicine.medical_specialty ,business.industry ,Brachydactyly ,Enamel hypoplasia ,medicine.disease ,Dental care ,Short stature ,Oral manifestations ,Pseudohypoparathyroidism ,Albright hereditary osteodystrophy ,lcsh:RK1-715 ,stomatognathic diseases ,stomatognathic system ,lcsh:Dentistry ,medicine ,Possible diagnosis ,medicine.symptom ,business ,General Dentistry ,Neurological problems - Abstract
Albright hereditary osteodystrophy is a disorder comprising phenotypic characteristics of genetic origin, such as short stature, obesity, and brachydactyly. It is a rare disorder and is related to pseudohypoparathyroidism. Within dentistry, it may be associated with enamel hypoplasia and late eruption. Furthermore, due to neurological problems, these patients may impose behavioural difficulties during dental appointments. The present study aims to describe the case of a patient with a possible diagnosis of Albright hereditary osteodystrophy, presenting symptoms and limitations to dental management.
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- 2018
9. Mosaicism for GNAS methylation defects associated with pseudohypoparathyroidism type 1B arose in early post-zygotic phases
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Paolo Bordogna, Maura Arosio, Giovanna Mantovani, Francesca Elli, and Anna Spada
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Male ,0301 basic medicine ,lcsh:QH426-470 ,lcsh:Medicine ,030105 genetics & heredity ,Biology ,Cell Line ,Epigenesis, Genetic ,Genomic Imprinting ,03 medical and health sciences ,GNAS ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Genetics ,medicine ,GNAS complex locus ,Humans ,Epigenetics ,Imprinting (psychology) ,Albright hereditary osteodystrophy ,Molecular Biology ,PTH resistance ,Genetics (clinical) ,Pseudohypoparathyroidism ,Mosaicism ,Research ,lcsh:R ,Imprinting ,Methylation ,DNA Methylation ,medicine.disease ,Uniparental disomy ,lcsh:Genetics ,Phenotype ,030104 developmental biology ,Methylation defects ,DNA methylation ,Cancer research ,biology.protein ,Female ,Genomic imprinting ,Developmental Biology - Abstract
Background Pseudohypoparathyroidism type 1B (PHP1B; MIM#603233) is a rare imprinting disorder (ID), associated with the GNAS locus, characterized by parathyroid hormone (PTH) resistance in the absence of other endocrine or physical abnormalities. Sporadic PHP1B cases, with no known underlying primary genetic lesions, could represent true stochastic errors in early embryonic maintenance of methylation. Previous data confirmed the existence of different degrees of methylation defects associated with PHP1B and suggested the presence of mosaicism, a phenomenon already described in the context of other IDs. Results With respect to mosaic conditions, the study of multiple tissues is a necessary approach; thus, we investigated somatic cell lines (peripheral blood and buccal epithelium and cells from the urine sediment) descending from different germ layers from 19 PHP patients (11 spor-PHP1B, 4 GNAS mutated PHP1A, and 4 PHP with no GNAS (epi)genetic defects) and 5 healthy controls. We identified 11 patients with epigenetic defects, further subdivided in groups with complete or partial methylation defects. The recurrence of specific patterns of partial methylation defects limited to specific CpGs was confirmed by checking methylation profiles of spor-PHP1B patients diagnosed in our lab (n = 56). Underlying primary genetic defects, such as uniparental disomy or deletion, potentially causative for the detected partial methylation were excluded in all samples. Conclusions Our data showed no differences of methylation levels between organs and tissues from the same patient, so we concluded that the epimutation occurred in early post-zygotic phases and that the partial defects were mosaics. The number of patients with no detectable (epi)genetic GNAS defects was too small to exclude epimutations occurring in later post-zygotic phases, affecting only selected tissues different from blood, thus leading to underdiagnosis during routine molecular diagnosis. Finally, we found no correlation between methylation ratios, representing the proportion of epimutated cells, and the clinical presentation, further confirming the hypothesis of a threshold effect of the GNAS loss of imprinting leading to an “all-or-none” phenotype. Electronic supplementary material The online version of this article (10.1186/s13148-018-0449-4) contains supplementary material, which is available to authorized users.
- Published
- 2018
10. Follow-up Findings in a Turkish Girl with Pseudohypoparathyroidism Type Ia Caused by a Novel Heterozygous Mutation in the GNAS Gene
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Beyhan Tüysüz, Sezgin Sahin, Susanne Thiele, Olcay Evliyaoğlu, and Olaf Hiort
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musculoskeletal diseases ,medicine.medical_specialty ,Heterozygote ,Adolescent ,Turkey ,Endocrinology, Diabetes and Metabolism ,DNA Mutational Analysis ,GNAS gene ,Parathyroid hormone ,Case Report ,medicine.disease_cause ,Short stature ,Endocrinology ,Internal medicine ,medicine ,GNAS complex locus ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Genetic Predisposition to Disease ,Albright hereditary osteodystrophy ,Child ,Pseudohypoparathyroidism ,Mutation ,Pseudohypoparathyroidism Ia ,ectopic ossification ,biology ,business.industry ,Brachydactyly ,Heterozygote advantage ,medicine.disease ,short stature ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,medicine.symptom ,Gsα activity ,business ,Hormone ,Follow-Up Studies - Abstract
Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by multihormone resistance and an Albright hereditary osteodystrophy (AHO) phenotype. It is caused by heterozygous mutations in GNAS gene. Clinical and biochemical findings of a female PHP-Ia patient were evaluated from age of diagnosis (6.5 years) to 14.5 years of age. The patient had short stature, brachydactyly, and subcutaneous heterotopic ossifications. Serum calcium and phosphorus levels were normal, but parathyroid hormone levels were high. Based on the typical clinical findings of AHO phenotype and biochemical findings, she was diagnosed as having PHP-Ia. A novel heterozygous mutation (c.128T>C) was found in the GNAS gene. Follow-up examinations revealed resistance to thyroid-stimulating hormone and a bioinactive growth hormone. Clinicians should take into consideration PHP-Ia in patients referred with short stature, and patients with an AHO phenotype must be further evaluated for hormone resistance, GNAS gene mutation, Gsα activity. To our knowledge, this is the first case report describing bioinactive growth hormone in PHP-Ia.
- Published
- 2017
11. Pseudohypoparathyroidism Type 1B with Asymptomatic Hypocalcemia
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Claudia Matta-Coelho, Joana Mesquita, and Selma B. Souto
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musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Calcitriol ,030209 endocrinology & metabolism ,030105 genetics & heredity ,Parathyroid Hormone Resistance ,Asymptomatic ,Gastroenterology ,Diseases of the endocrine glands. Clinical endocrinology ,Albright hereditary osteodystrophy ,03 medical and health sciences ,Hyperphosphatemia ,0302 clinical medicine ,Internal medicine ,Rare case ,Female patient ,Medicine ,business.industry ,Pseudohypoparathyroidism Type 1b ,General Medicine ,RC648-665 ,medicine.disease ,medicine.symptom ,business ,medicine.drug - Abstract
Objective: To report the rare case of an asymptomatic female patient with pseudohypoparathyroidism type 1b.Methods: The diagnosis of pseudohypoparathyroidism type 1b was confirmed by analysis of the methylation status by methylation-specific multiplex ligation-dependent probe amplification.Results: A 21-year-old female was referred to the endocrinology clinic due to an elevated parathyroid hormone level as an incidental finding. Her personal and family histories were unremarkable and there were no Albright hereditary osteodystrophy stigmata. Initially the patient only presented an elevated parathyroid hormone level, without hypocalcemia or hyperphosphatemia. The patient exhibited no signs or symptoms of hypocalcemia. After 6 months the patient presented hypocalcemia and treatment with calcium and calcitriol was commenced, despite her remaining asymptomatic. The genetic study was compatible with sporadic pseudohypoparathyroidism type 1b.Conclusion: An incidental finding of elevated parathyroid hormone with absence of Albright hereditary osteodystrophy phenotype raised the clinical suspicion of pseudohypoparathyroidism type 1b, which lead to careful monitoring of calcemia and therefore allowed timely management of hypocalcemia.Abbreviations: AHO Albright hereditary osteodystrophy GNAS guanine nucleotide binding protein, alpha stimulating gene Gsα alpha subunit of G protein PHP pseudohypoparathyroidism PHP-1a pseudohypoparathyroidism type 1a PHP-1b pseudohypoparathyroidism type 1b PHP-1c pseudohypoparathyroidism type 1c PHP-2 pseudohypoparathyroidism type 2 PTH parathyroid hormone
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- 2018
12. 2q37 Deletions in Patients With an Albright Hereditary Osteodystrophy Phenotype and PTH Resistance
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Paolo Bordogna, Bruno Madeo, Luisa De Sanctis, Francesca Elli, Giovanna Mantovani, Maria Antonia Maffini, Maura Arosio, and Arianna Pirelli
- Subjects
0301 basic medicine ,2q37 deletion ,Albright hereditary osteodystrophy ,Brachydactyly-mental retardation syndrome ,GNAS ,Pseudohypoparathyroidism ,Endocrinology, Diabetes and Metabolism ,Parathyroid hormone ,030209 endocrinology & metabolism ,Bioinformatics ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pathognomonic ,GNAS complex locus ,Medicine ,Original Research ,lcsh:RC648-665 ,biology ,business.industry ,pseudohypoparathyroidism ,medicine.disease ,Phenotype ,030104 developmental biology ,biology.protein ,Pseudopseudohypoparathyroidism ,Differential diagnosis ,business ,brachydactyly-mental retardation syndrome ,Hormone - Abstract
Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients.
- Published
- 2019
13. A Case of Soft Tissue Ossifications: A Case Report
- Author
-
Paolo Arrigoni and Alessandro Minen
- Subjects
medicine.medical_specialty ,Adolescent ,Aftercare ,Pain ,Physical examination ,Albright hereditary osteodystrophy ,medicine ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Orthopedics and Sports Medicine ,Hip pain ,medicine.diagnostic_test ,Ossification ,business.industry ,Ossification, Heterotopic ,Brachydactyly ,Anti-Inflammatory Agents, Non-Steroidal ,Soft tissue ,medicine.disease ,Dermatology ,Radiography ,Phenotype ,Treatment Outcome ,Myositis Ossificans ,Fibrodysplasia ossificans progressiva ,Pseudohypoparathyroidism ,Pseudopseudohypoparathyroidism ,Surgery ,Female ,Hip Joint ,medicine.symptom ,business - Abstract
Case A patient who had previously been diagnosed with fibrodysplasia ossificans progressiva was seen for hip pain and progressive soft tissue ossifications. Through a careful clinical examination, by which a subtype of brachydactyly was noted, the Albright hereditary osteodystrophy phenotype was recognized, and a new diagnosis of pseudopseudohypoparathyroidism was established. This paucisymptomatic condition often remains unidentified; however, its transmission can lead to more potentially serious diseases. Conclusions A careful diagnostic process, including physical examination, is essential. Even if advanced tests exist, small clinical findings can lead to the proper conclusion. In our case, a finger pointed us in the right direction.
- Published
- 2019
14. Brachydactyly Mental Retardation Syndrome Diagnosed in Adulthood
- Author
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Issac Sachmechi, Rupak Mahendhar, Radu Butuc, Maia Natalia Pavlovic, and Paria Zarghamravanbakhsh
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,albright hereditary osteodystrophy ,medicine.diagnostic_test ,2q37 deletion syndrome ,business.industry ,Craniofacial abnormality ,Brachydactyly ,General Engineering ,Endocrinology/Diabetes/Metabolism ,brachydactyly ,Parathyroid hormone ,030105 genetics & heredity ,medicine.disease ,Phenotype ,03 medical and health sciences ,Internal Medicine ,Medicine ,Autism ,Pseudopseudohypoparathyroidism ,business ,Chromosomal Deletion ,Genetic testing - Abstract
Brachydactyly mental retardation syndrome (BDMR) is due to a rare, small chromosomal deletion of 2q37, and manifests with variable signs and symptoms in people who live with it. BDMR could be misdiagnosed as Albright hereditary osteodystrophy (AHO), because it presents with lack of hormone resistance to parathyroid hormone (PTH) and similar skeletal and craniofacial abnormalities; however, BDMR is far rarer and can present with a different phenotype. In some cases, BDMR patients exhibit malformations of the internal organs, which could cause life-threatening health issues. Associations have also been made between this chromosomal deletion and autism as well. We here report a case of BDMR with an AHO-like phenotype: mild mental retardation, along with normal calcium, phosphate, and PTH levels. Since our patient had a normal biochemical test, we considered pseudopseudohypoparathyroidism (PPHP) as the diagnosis and genetic testing was performed. Karyotype analysis showed deletion of the long q-arm of chromosome 2 in all analyzed cells-46 XX, del (2)(q37.1), which was consistent with BDMR. This deletion is a loss of around 100 genes that can present itself in various ways neurologically and physiologically, depending on the genes lost. However, because patients experience a range of symptoms such as autism, seizures, heart defects, brachydactyly, there could be unforeseen complications with BDMR. Therefore, we postulate that it is necessary to consider a diagnosis of BDMR in adults with AHO-like phenotype and normal calcium metabolism.
- Published
- 2018
15. Diagnosis and management of pseudohypoparathyroidism and related disorders:first international Consensus Statement
- Author
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Susanne Thiele, Eileen M. Shore, Luisa De Sanctis, Thomas Eggermann, Serap Turan, Murat Bastepe, Gabriel Á. Martos-Moreno, Aurora Garcia Ramirez, Vrinda Saraff, Nina Knight, Caroline Silve, Outi Mäkitie, Agnès Linglart, Marie Laure Kottler, Emily L. Germain-Lee, Rebecca Rodado, Philip Murray, Peter Kamenický, Lars Rejnmark, Masanori Minagawa, Anya Rothenbuhler, Kathleen Freson, Timothee Choplin, Alessia Usardi, Francesca Elli, Regina Matsunaga Martin, M. Carola Zillikens, Guillemette Devernois, Harald Jüppner, David Monk, Arrate Pereda, Neveen A. T. Hamdy, Gianpaolo de Filippo, Lionel Groussin, Elvire Le Norcy, Robert J. Pignolo, Ashley H. Shoemaker, Giovanna Mantovani, Olaf Hiort, Roberto Bufo, Guiomar Perez de Nanclares, Michael A. Levine, Beatriz Lecumberri, Philip Woods, Patrick Hanna, S Faisal Ahmed, Mantovani, Giovanna, Bastepe, Murat, Monk, David, de Sanctis, Luisa, Thiele, Susanne, Usardi, Alessia, Ahmed, S. Faisal, Bufo, Roberto, Choplin, Timothee, De Filippo, Gianpaolo, Devernois, Guillemette, Eggermann, Thomas, Elli, Francesca M., Freson, Kathleen, Garcia Ramirez, Aurora, Germain-Lee, Emily L., Groussin, Lionel, Hamdy, Neveen, Hanna, Patrick, Hiort, Olaf, Juppner, Harald, Kamenicky, Peter, Knight, Nina, Kottler, Marie-Laure, Le Norcy, Elvire, Lecumberri, Beatriz, Levine, Michael A., Makitie, Outi, Martin, Regina, Angel Martos-Moreno, Gabriel, Minagawa, Masanori, Murray, Philip, Pereda, Arrate, Pignolo, Robert, Rejnmark, Lars, Rodado, Rebecca, Rothenbuhler, Anya, Saraff, Vrinda, Shoemaker, Ashley H., Shore, Eileen M., Silve, Caroline, Turan, Serap, Woods, Philip, Zillikens, M. Carola, Perez de Nanclares, Guiomar, Linglart, Agnes, Clinicum, Lastentautien yksikkö, Children's Hospital, HUS Children and Adolescents, Internal Medicine, UAM. Departamento de Medicina, UAM. Departamento de Pediatría, Instituto de Investigación del Hospital de La Princesa (IP), Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Università degli Studi di Milano = University of Milan (UNIMI), Harvard Medical School [Boston] (HMS), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Università degli studi di Torino = University of Turin (UNITO), Lübeck University of Applied Sciences, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Glasgow, Italian Progressive Osseous Heteroplasia Association (IPOHA), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Connecticut Children's Medical Center, University of Connecticut (UCONN), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université Paris Descartes - Paris 5 (UPD5), Leiden University Medical Center (LUMC), Universiteit Leiden, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Endocrine Unit, Massachusetts General Hospital [Boston], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Génétique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Pathologies, Imagerie et Biothérapies oro-faciales (EA 2496), Hospital Universitario La Paz, Department of Statistics [West Lafayette], Purdue University [West Lafayette], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universidade de São Paulo = University of São Paulo (USP), Chiba University Hospital, Manchester University NHS Foundation Trust (MFT), Bioaraba Health Research Institute, Mayo Clinic [Rochester], Aarhus University Hospital, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Birmingham Children’s Hospital, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], University of Pennsylvania, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marmara University [Kadıköy - İstanbul], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Medicine and Pediatrics, Department of Pediatrics, University of Turin, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF)-PSL Research University (PSL), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Center for Molecular and Vascular Biology, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], Endocrine Unit, Department of Medicine, and Pediatric Neprology Unit, MassGeneral Hospital for Children, Servicio de Endocrinología, Hospital Universitario La Paz, Hospital for Children and Adolescents, Helsinki University Central Hospital, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Laboratorio de Genética Molecular, Unidad de Investigación, Hospital de Txagorritxu, University of Milan, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), University of Helsinki, University of São Paulo (USP), University of Pennsylvania [Philadelphia], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,0301 basic medicine ,Pediatrics ,Delayed Diagnosis ,Endocrinology, Diabetes and Metabolism ,Endocrinology ,Statement (logic) ,Drug Resistance ,Parathyroid hormone ,MESH: Risk Assessment ,Pseudohypoparathyroidism/diagnosis ,STIMULATORY G-PROTEIN ,Neonatal Screening/organization & administration ,0302 clinical medicine ,MESH: Practice Guidelines as Topic ,Program Development ,BRACHYDACTYLY TYPE-E ,PARATHYROID-HORMONE RESISTANCE ,Disorders ,IMPRINTING CONTROL ELEMENT ,MESH: Infant, Newborn ,MESH: Pseudohypoparathyroidism ,MESH: Genetic Predisposition to Disease ,Prognosis ,3. Good health ,Diabetes and Metabolism ,MESH: Parathyroid Hormone ,IDENTIFIES PDE4D MUTATIONS ,Parathyroid Hormone ,NUCLEOTIDE REGULATORY PROTEIN ,Consensus statement ,Pseudohypoparathyroidism ,Practice Guidelines as Topic ,MESH: Drug Resistance ,Female ,medicine.symptom ,Parathyroid Hormone/therapeutic use ,medicine.medical_specialty ,Consensus ,Delayed Diagnosis/adverse effects ,Medicina ,030209 endocrinology & metabolism ,PROGRESSIVE OSSEOUS HETEROPLASIA ,Parathyroid Hormone Resistance ,Risk Assessment ,Short stature ,PATERNAL UNIPARENTAL DISOMY ,Article ,MESH: Prognosis ,Growth hormone deficiency ,GNAS INACTIVATING MUTATIONS ,03 medical and health sciences ,Neonatal Screening ,BECKWITH-WIEDEMANN SYNDROME ,MESH: Program Development ,medicine ,Humans ,Genetic Predisposition to Disease ,MESH: Consensus ,MESH: Neonatal Screening ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,GS-ALPHA-GENE ,MESH: Humans ,ALBRIGHT HEREDITARY OSTEODYSTROPHY ,business.industry ,Brachydactyly ,Infant, Newborn ,Type 2 Diabetes Mellitus ,medicine.disease ,MESH: Male ,MESH: Delayed Diagnosis ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Diagnosis and management ,DEPENDENT PROBE AMPLIFICATION ,Family medicine ,3121 General medicine, internal medicine and other clinical medicine ,business ,MESH: Female ,Neurocognitive - Abstract
This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders, This Consensus Statement and the series of consensus meetings were supported by funds from the European Cooperation in Science and Technology (COST) action BM1208 on imprinting disorders (www.imprinting- disorders.eu), the European Society for Paediatric Endocrinology (ESPE) and the European Society for Endocrinology (ESE). Travel costs and housing of the representatives of the Asian Pacific Paediatric Endocrine Society (APPES) and of the Pediatric Endocrine Society (PES) were supported by their societies. The authors received no funding from pharmaceutical companies
- Published
- 2018
16. Classic and Non-Classic Features in Pseudohypoparathyroidism: Case Study and Brief Literature Review
- Author
-
Muhammad Uzair Lodhi, Mustafa Rahim, and Aaron R Kuzel
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Brachydactyly ,General Engineering ,Parathyroid hormone ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,medicine.disease ,Short stature ,Albright hereditary osteodystrophy ,03 medical and health sciences ,0302 clinical medicine ,Intellectual disability ,medicine ,Osteodystrophy ,medicine.symptom ,business ,Pseudohypoparathyroidism - Abstract
Pseudohypoparathyroidism is a rare condition that is due to a defect in the stimulatory G-protein coupled receptor, resulting in end-organ resistance to parathyroid hormone. Hereditary forms of pseudohypoparathyroidism present with certain classic features such as obesity, short stature, brachydactyly, and intellectual disability. Constellation of these physical features is known as Albright's hereditary osteodystrophy. In this case, 41-year-old male presented with the classic features of pseudohypoparathyroidism and with 59 lbs weight gain over six months. It was determined that the cause of the patient's weight gain was due to concomitant hypothyroidism, which is a common association. There are several non-classic features and associated pathologies associated with pseudohypoparathyroidism. These conditions should be regularly screened for and assessed when a patient presents with pseudohypoparathyroidism.
- Published
- 2017
17. A positive genotype–phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene
- Author
-
Benedikt Reiz, Susanne Thiele, Joachim Grötzinger, Dagmar Struve, Bettina Brix, Pia Staedt, Olaf Hiort, Jennane Farida, and Ralf Werner
- Subjects
Parathyroid hormone ,Correlation ,Exon ,GNAS ,Genetics ,GNAS complex locus ,Medicine ,Pseudohypoparathyroidism type Ia ,Missense mutation ,Gsα ,Albright hereditary osteodystrophy ,Molecular Biology ,Genetics (clinical) ,Pseudohypoparathyroidism ,biology ,business.industry ,pseudohypoparathyroidism ,Original Articles ,genotype–phenotype correlation ,medicine.disease ,RNA splicing ,biology.protein ,mutation ,business ,G proteins - Abstract
Maternally inherited inactivating GNAS mutations are the most common cause of parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO) leading to pseudohypoparathyroidism type Ia (PHPIa) due to Gsα deficiency. Paternally inherited inactivating mutations lead to isolated AHO signs characterizing pseudo-pseudohypoparathyroidism (PPHP). Mutations are distributed throughout the Gsα coding exons of GNAS and there is a lack of genotype–phenotype correlation. In this study, we sequenced exon 1–13 of GNAS in a large cohort of PHPIa- and PPHP patients and identified 58 different mutations in 88 patients and 27 relatives. Thirty-three mutations including 15 missense mutations were newly discovered. Furthermore, we found three hot spots: a known hotspot (p.D190MfsX14), a second at codon 166 (p.R166C), and a third at the exon 5 acceptor splice site (c.435 + 1G>A), found in 15, 5, and 4 unrelated patients, respectively. Comparing the clinical features to the molecular genetic data, a significantly higher occurrence of subcutaneous calcifications in patients harboring truncating versus missense mutations was demonstrated. Thus, in the largest cohort of PHPIa patients described to date, we extend the spectrum of known GNAS mutations and hot spots and demonstrate for the first time a correlation between the genetic defects and the expression of a clinical AHO-feature.
- Published
- 2014
18. GNAS Mutations in Pseudohypoparathyroidism Type 1a and Related Disorders
- Author
-
Manuel C. Lemos and Rajesh V. Thakker
- Subjects
medicine.medical_specialty ,progressive osseous heteroplasia ,Gs-alpha ,Biology ,Progressive osseous heteroplasia ,Frameshift mutation ,GNAS ,Genomic Imprinting ,Germline mutation ,Molecular genetics ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Genetics ,medicine ,GNAS complex locus ,Animals ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Albright hereditary osteodystrophy ,Genetic Association Studies ,Genetics (clinical) ,Pseudohypoparathyroidism ,Mutation Update ,Ossification, Heterotopic ,pseudohypoparathyroidism ,Skin Diseases, Genetic ,medicine.disease ,Bone Diseases, Metabolic ,Mutation ,biology.protein ,Pseudopseudohypoparathyroidism ,pseudopseudohypoparathyroidism - Abstract
Pseudohypoparathyroidism type 1a (PHP1a) is characterized by hypocalcaemia and hyperphosphatemia due to parathyroid hormone resistance, in association with the features of Albright's hereditary osteodystrophy (AHO). PHP1a is caused by maternally inherited inactivating mutations of Gs-alpha, which is encoded by a complex imprinted locus termed GNAS. Paternally inherited mutations can lead either to pseudopseudohypoparathyroidism (PPHP) characterized by AHO alone, or to progressive osseous heteroplasia (POH), characterized by severe heterotopic ossification. The clinical aspects and molecular genetics of PHP1a and its related disorders are reviewed together with the 343 kindreds with Gs-alpha germline mutations reported so far in the literature. These 343 (176 different) mutations are scattered throughout the 13 exons that encode Gs-alpha and consist of 44.9% frameshift, 28.0% missense, 14.0% nonsense, and 9.0% splice-site mutations, 3.2% in-frame deletions or insertions, and 0.9% whole or partial gene deletions. Frameshift and other highly disruptive mutations were more frequent in the reported 37 POH kindreds than in PHP1a/PPHP kindreds (97.3% vs. 68.7%, P < 0.0001). This mutation update and respective genotype–phenotype data may be of use for diagnostic and research purposes and contribute to a better understanding of these complex disorders.
- Published
- 2014
19. Diffuse Symmetric Cerebral Calcifications: An Emerging Clinical Pivot
- Author
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Constantine Farmakidis and Jacob R. Hascalovici
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Cerebral calcification ,business.industry ,Brain ,Calcinosis ,General Medicine ,Middle Aged ,medicine.disease ,Albright hereditary osteodystrophy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Pseudohypoparathyroidism ,medicine ,Humans ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Published
- 2016
20. Clinical and radiological findings in a case of pseudohypoparathyroidism type 1a: Albright hereditary osteodystrophy
- Author
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Jesús Pozo-Román, M.T. Muñoz-Calvo, Jesús Argente, M. Sanz-Fernández, and Gabriel Á. Martos-Moreno
- Subjects
business.industry ,Pseudohypoparathyroidism Type 1a ,medicine.disease ,Pediatrics ,RJ1-570 ,Albright hereditary osteodystrophy ,Tomography x ray computed ,X ray computed ,Management of Technology and Innovation ,Radiological weapon ,Medicine ,business ,Nuclear medicine ,Pseudohypoparathyroidism - Published
- 2015
21. GNAS and McCune-Albright/Fibrous Dysplasia, Albright Hereditary Osteodystrophy, and Pseudohypoparathyroidism
- Author
-
Lee S. Weinstein
- Subjects
Albright hereditary osteodystrophy ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Fibrous dysplasia ,medicine ,GNAS complex locus ,biology.protein ,medicine.disease ,business ,Pseudohypoparathyroidism - Published
- 2016
22. Madelung Deformity in a Girl With a Novel and De Novo Mutation in the GNAS Gene
- Author
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Birgit Sikkema-Raddatz, Jan D. H. Jongbloed, Rob B. van der Luijt, Eva Klopocki, Patrick Rump, Stefan Mundlos, and Cardiovascular Centre (CVC)
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,albright hereditary osteodystrophy ,Adolescent ,media_common.quotation_subject ,Molecular Sequence Data ,Mutation, Missense ,Wrist ,Biology ,LERI-WEILL DYSCHONDROSTEOSIS ,STIMULATORY G-PROTEIN ,Exon ,GNAS ,Internal medicine ,Genetics ,medicine ,GNAS complex locus ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Abnormalities, Multiple ,Girl ,Léri–Weill dyschondrosteosis ,Genetics (clinical) ,media_common ,Subluxation ,Base Sequence ,ABNORMALITIES ,IA ,madelung deformity ,DELETION ,Ulna ,Brachydactyly ,fungi ,brachydactyly type E ,Anatomy ,Sequence Analysis, DNA ,medicine.disease ,Radiography ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,Female ,SHOX - Abstract
Madelung deformity, a congenital anomaly of the wrist with subluxation of the ulna head, is not a widely recognized feature of Albright hereditary osteodystrophy. Here, we describe a young female with a bilateral Madelung deformity, mild cognitive disability, some dysmorphic facial features, and a type E-like brachydactyly, in whom we identified a novel and de novo mutation (c.476T>C; p.Val159Ala) in exon 6 of the GNAS gene. (C) 2011 Wiley-Liss, Inc.
- Published
- 2011
23. Obesity and calcinosis cutis: characteristic early signs of infantile pseudohypoparathyroidism
- Author
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Jin Soon Hwang, Young Bae Sohn, Eun-So Lee, Jae Ho Cho, and Ji-Youn Park
- Subjects
Pediatrics ,medicine.medical_specialty ,Early signs ,business.industry ,Dermatology ,medicine.disease ,Obesity ,Calcinosis cutis ,Albright hereditary osteodystrophy ,Orthopedic surgery ,medicine ,Medical genetics ,business ,Pseudohypoparathyroidism - Abstract
ejd.2013.2045 Auteur(s) : Ji-Youn Park1, Young Bae Sohn2, Jae Ho Cho3, Jin Soon Hwang4, Eun-So Lee1 esl@ajou.ac.kr 1 Department of Dermatology, 2 Department of Medical Genetics, 3 Department of Orthopedic Surgery, 4 Department of Pediatrics, Ajou University School of Medicine, San 5 Woncheon-dong, Yeongtong-gu, Suwon 443-721, Republic of Korea Calcinosis cutis in infancy is rare, and is associated with genetic disorders, like Albright hereditary osteodystrophy (AHO) [1]. AHO is characterized by [...]
- Published
- 2013
24. Evidence of hormone resistance in a pseudo-pseudohypoparathyroidism patient with a novel paternal mutation in GNAS
- Author
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Susanne Thiele, Saygin Abali, Bettina Brix, Belma Haliloglu, Zeynep Atay, Murat Bastepe, Olta Tafaj, Abdullah Bereket, Serap Turan, Turan, Serap, Thiele, Susanne, Tafaj, Olta, Brix, Bettina, Atay, Zeynep, Abali, Saygin, Haliloglu, Belma, Bereket, Abdullah, and Bastepe, Murat
- Subjects
Male ,medicine.medical_specialty ,Histology ,Adolescent ,Physiology ,Endocrinology, Diabetes and Metabolism ,PATHOGENESIS ,DNA Mutational Analysis ,Parathyroid hormone ,Context (language use) ,Biology ,medicine.disease_cause ,Short stature ,G(S)ALPHA ,Article ,GNAS ,Fathers ,Internal medicine ,medicine ,GNAS complex locus ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Allele ,Hormone resistance ,Vitamin D ,Pseudohypoparathyroidism ,Alleles ,Mutation ,ALBRIGHT HEREDITARY OSTEODYSTROPHY ,IA ,Infant, Newborn ,ASSOCIATION ,medicine.disease ,GENE ,DEFICIENCY ,Endocrinology ,Parathyroid Hormone ,MATERNAL TRANSMISSION ,biology.protein ,Pseudopseudohypoparathyroidism ,Calcium ,Female ,XL-ALPHA-S ,medicine.symptom - Abstract
Context: Loss-of-function GNAS mutations lead to hormone resistance and Albright's hereditary osteodystrophy (AHO) when maternally inherited, i.e. pseudohypoparathyroidism-Ia (PHPIa), but cause AHO alone when located on the paternal allele, i.e. pseudoPHP (PPHP). Objective: We aimed to establish the molecular diagnosis in a patient with AHO and evidence of hormone resistance. Case: The patient is a female who presented at the age of 13.5 years with short stature and multiple AHO features. No evidence for TSH or gonadotropin-resistance was present. Serum calcium and vitamin D levels were normal. However, serum PTH was elevated on multiple occasions (64-178 pg/mL, normal: 9-52) and growth hormone response to clonidine or L-DOPA was blunted, suggesting hormone resistance and PHP-Ia. The patient had diminished erythrocyte Gm activity and a novel heterozygous GNAS mutation (c.328 G>C; p.A109P). The mother lacked the mutation, and the father's DNA was not available. Hence, a diagnosis of PPHP also appeared possible, supported by low birth weight and a lack of AHO features associated predominantly with PHP-Ia, i.e. obesity and cognitive impairment. To determine the parental origin of the mutation, we amplified the paternally expressed A/B and biallelically expressed Gs alpha transcripts from the patient's peripheral blood RNA. While both wild-type and mutant nucleotides were detected in the Gs alpha amplicon, only the mutant nucleotide was present in the A/B amplicon, indicating that the mutation was paternal. Conclusion: These findings suggest that PTH and other hormone resistance may not be an exclusive feature of PHP-Ia and could also be observed in patients with PPHP. (C) 2014 Elsevier Inc. All rights reserved.
- Published
- 2014
25. Albright Hereditary Osteodystrophy: A Case Report
- Author
-
Deepa Hugar, Santosh Hugar, Megha Kadani, and Sangameshwar Sajjanshetty
- Subjects
musculoskeletal diseases ,Pediatrics ,medicine.medical_specialty ,Clinical Biochemistry ,lcsh:Medicine ,Oral cavity ,Short stature ,Albright hereditary osteodystrophy ,Hyperphosphatemia ,Internal medicine ,medicine ,Pseudohypoparathyroidism ,albright hereditary osteodystrophy (aho) ,business.industry ,Metabolic disorder ,Brachydactyly ,lcsh:R ,brachydactyly ,pseudohypoparathyroidism ,General Medicine ,medicine.disease ,Dentistry Section ,Endocrinology ,Male patient ,medicine.symptom ,business - Abstract
A dental practitioner with an eagle’s eye can diagnose many hidden disease through careful examination of the oral cavity. One such hereditary metabolic disorder is Albright hereditary osteodystrophy (AHO). Characteristic presentations in an individual affected by AHO were short stature, obesity and brachydactyly especially of 4th and 5th digits, which are the phenotypic features of genetic mutation. Pseudohypoparathyroidism (PHP) is characterized by inability of the body to respond appropriately to parathormone, mainly characterized by hypocalcemia, increased serum parathormone concentration, insensitivity to the biological activity of parathormone and hyperphosphatemia. AHO when seen in association with resistance to parathormone (PTH), it is called PHP. Here is, a case report of 32-year-old male patient with AHO with distinctive physical characteristics and oral manifestations.
- Published
- 2014
26. A 22-year-old woman with hypocalcemia and clinical features of albright hereditary osteodystrophy diagnosed with sporadic pseudohypoparathyroidism type Ib using a methylation-specific multiplex ligation-dependent probe amplification assay
- Author
-
Satoshi Zeniya, Akiko Yuno, Yoshitaka Uno, Hirotomo Miake, Yurie Moriki, Takeshi Usui, and Takayuki Watanabe
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Parathyroid hormone ,Gastroenterology ,Methylation ,Albright hereditary osteodystrophy ,Diagnosis, Differential ,Hyperphosphatemia ,Young Adult ,Internal medicine ,Internal Medicine ,medicine ,Pseudohypoparathyroidism type Ia ,Humans ,natural sciences ,Multiplex ligation-dependent probe amplification ,Genetic Testing ,Pseudohypoparathyroidism ,Genetic testing ,medicine.diagnostic_test ,Hypocalcemia ,business.industry ,General Medicine ,DNA ,medicine.disease ,Endocrinology ,Female ,business ,Multiplex Polymerase Chain Reaction - Abstract
A 22-year-old woman presented to us with seizures of a few minutes duration. She had clinical features of Albright hereditary osteodystrophy (AHO), including hypocalcemia, hyperphosphatemia and resistance to parathyroid hormone. Genetic testing revealed a sporadic form of pseudohypoparathyroidism type Ib (PHP-Ib). This is the first Japanese case involving overlap between pseudohypoparathyroidism type Ia (PHP Ia) associated with AHO and PHP Ib. It is important to perform both DNA sequencing and methylation status analyses in cases of suspected PHP in patients with signs of AHO.
- Published
- 2014
27. Screening of genes involved in cAMP-mediated signalling in a large Italian series of patients affected with Albright hereditary osteodystrophy and/or Pseudohypoparathyroidism
- Author
-
Paolo Bordogna, Anna Spada, Sanctis Luisa de, Giovanna Mantovani, and Francesca Elli
- Subjects
Albright hereditary osteodystrophy ,medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,medicine.disease ,business ,Gene ,Pseudohypoparathyroidism - Published
- 2014
28. Albright Hereditary Osteodystrophy
- Author
-
Ulrike Blume-Peytavi, Dirk Schnabel, Karola Stieler, Saman Atugoda, and Wolfram Sterry
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,biology ,business.industry ,Fibrous dysplasia ,Dermatology ,medicine.disease ,Osteochondrodysplasia ,body regions ,Albright hereditary osteodystrophy ,Endocrinology ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,GNAS complex locus ,biology.protein ,Skin pathology ,business ,Osteoma ,Pseudohypoparathyroidism ,Rare disease - Abstract
Albright hereditary osteodystrophy with pseudohypoparathyroidism is due to maternal loss-of-function mutations in the GNAS gene. Its typical clinical features encompass obesity, a round face and a short neck, osteoma of the skin, endocrinological abnormalities, and psychomotoric retardation. Here we present a 10-month-old Tunisian boy with a classical course of this rare disease.
- Published
- 2010
29. Pseudohypoparathyroidism and GNAS Epigenetic Defects: Clinical Evaluation of Albright Hereditary Osteodystrophy and Molecular Analysis in 40 Patients
- Author
-
B.L. Clarke
- Subjects
Albright hereditary osteodystrophy ,biology ,business.industry ,medicine ,GNAS complex locus ,biology.protein ,Epigenetics ,Bioinformatics ,medicine.disease ,business ,Clinical evaluation ,Pseudohypoparathyroidism ,Molecular analysis - Published
- 2010
30. Deletion 3q22.1–q23 with blepharophimosis, ptosis and epicanthus inversus and an Albright hereditary osteodystrophy-like brachydactyly phenotype
- Author
-
Marion S. Croft and Peter D. Turnpenny
- Subjects
medicine.medical_specialty ,Adolescent ,Foot Deformities, Congenital ,Blepharophimosis ,Fibrous Dysplasia, Polyostotic ,Pathology and Forensic Medicine ,Albright hereditary osteodystrophy ,Ptosis ,Chronic kidney disease-mineral and bone disorder ,medicine ,Blepharoptosis ,Humans ,Abnormalities, Multiple ,Genetics (clinical) ,Chronic Kidney Disease-Mineral and Bone Disorder ,Hand deformity ,business.industry ,Fibrous dysplasia ,Brachydactyly ,Eyelids ,General Medicine ,medicine.disease ,Phenotype ,Dermatology ,Pediatrics, Perinatology and Child Health ,Female ,Chromosomes, Human, Pair 3 ,Chromosome Deletion ,Anatomy ,medicine.symptom ,business ,Hand Deformities, Congenital - Published
- 2008
31. Pseudohypoparathyroidism-albright hereditary osteodystrophy
- Author
-
Sanjay Gupta, Puneet Misra, Shantanu Rastogi, and Deepa Rastogi
- Subjects
medicine.medical_specialty ,Pediatrics ,Adolescent ,High index ,Fibrous Dysplasia, Polyostotic ,Short stature ,Thyroid function tests ,Diagnosis, Differential ,Albright hereditary osteodystrophy ,Basal Ganglia Diseases ,medicine ,Humans ,Coarse facies ,Pseudohypoparathyroidism ,medicine.diagnostic_test ,business.industry ,Calcinosis ,medicine.disease ,Response to treatment ,Surgery ,Pediatrics, Perinatology and Child Health ,Female ,medicine.symptom ,Tomography, X-Ray Computed ,business - Abstract
A 13 year old girl with short stature, and retarded mental growth with coarse facies and deranged thyroid function test was initially suspected as a case of hypothyroidism and was started on thyroxine. Lack of response to treatment and on further investigations it was diagnosed as a case of pseudohypoparathyroidism. High index of suspicion and careful evaluation, is important to diagnose such an entity.
- Published
- 1998
32. [Untitled]
- Author
-
Meral Gunay-Aygun, R. D. Nicholls, and S. B. Cassidy
- Subjects
Genetics ,education.field_of_study ,Cohen syndrome ,business.industry ,Mechanism (biology) ,Population ,Constitutional obesity ,Bioinformatics ,medicine.disease ,Obesity ,Albright hereditary osteodystrophy ,Bardet–Biedl syndrome ,Medicine ,Genomic imprinting ,business ,education ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics - Abstract
Constitutional obesity and mental retardation cooccur in several multiple congenital anomaly syndromes, including Prader–Willi syndrome, Bardet–Biedl syndrome, Cohen syndrome, Albright hereditary osteodystrophy, and Borjeson–Forssman–Lehmann syndrome as well as some rarer disorders. Although hypothalamic–pituitary axis abnormalities are thought to be a possible causative mechanism in some of these disorders, current knowledge is insufficient to explain the pathophysiologic mechanism of obesity in most multiple congenital anomaly/mental retardation syndromes. The chromosomal location of many of these syndromes is known, and studies are ongoing to identify the causative genes. Further delineation of the functions of the underlying genes will likely be instructive regarding mechanisms of appetite, satiety, and obesity in the general population. This review details current knowledge of the clinical and molecular genetic findings of multiple congenital anomaly/mental retardation syndromes associated with intrinsic obesity in an effort to delineate causative mechanisms and genetic abnormalities contributing to obesity.
- Published
- 1997
33. Bariatric surgery in an obese patient with Albright hereditary osteodystrophy: a case report
- Author
-
Luc Portmann, Giacomo Gastaldi, Vittorio Giusti, and Chiara Ferrario
- Subjects
Medicine(all) ,musculoskeletal diseases ,medicine.medical_specialty ,Pathology ,endocrine system diseases ,Roux-en-Y gastric bypass ,Pseusopseudohypoparathyroidism ,business.industry ,General surgery ,Gastric bypass ,nutritional and metabolic diseases ,Case Report ,General Medicine ,medicine.disease ,body regions ,Albright hereditary osteodystrophy ,surgical procedures, operative ,Surgical oncology ,Medicine ,Calcium ,Pseudopseudohypoparathyroidism ,Bone ,business - Abstract
INTRODUCTION: We report for the first time the case of a patient with Albright hereditary osteodystrophy and pseudopseudohypoparathyroidism who underwent a Roux-en-Y gastric bypass. CASE PRESENTATION: A 26-year-old obese Caucasian woman with Albright hereditary osteodystrophy with pseudopseudohypoparathyroidism (heterozygous mutation (L272F) in GNAS1 exon 10 on molecular analysis) was treated with gastric bypass. She had the classical features of Albright hereditary osteodystrophy: short stature (138cm), obesity (body mass index 49.5kg/m2), bilateral shortening of the fourth and fifth metacarpals, short neck, round and wide face with bombed front and small eyes. Before the gastric bypass was performed, biochemical determination revealed a slightly low serum calcium level (2.09mmol/L; normal range 2.1 to 2.5mmol/l), and an elevated parathyroid hormone level (87ng/L; normal range 10 to 70ng/L) associated with low vitamin D level (19μg/L; normal range 30 to 50μg/L). Vitamin D supplementation was prescribed before surgery. After the Roux-en-Y gastric bypass, she achieved a progressive substantial weight loss, from 94kg (body mass index 49.5kg/m2) to 49kg (body mass index 25.9kg/m2) in one year. Her weight then stabilized at 50kg (body mass index 26kg/m2) during our three years of follow-up. Before the operation and every three months after it, she was screened for nutritional deficiencies, and serum markers of bone turnover and renal function were monitored. Considering the deficiencies in zinc, magnesium, calcium, vitamin D and vitamin B12, appropriate supplementation was prescribed. Before and two years after the Roux-en-Y gastric bypass, a dual-energy X-ray absorptiometry assessment of bone density was performed that showed no changes on her lumbar column (0.882g/cm2 and both T-score and Z-score of -1.5 standard deviation). In addition, bone microarchitecture with a measurement of her trabecular bone score was found to be normal. CONCLUSION: This is the first case of Roux-en-Y gastric bypass described in a patient with pseudopseudohypoparathyroidism showing that such a procedure seems to be safe in obese patients with Albright hereditary osteodystrophy and pseudopseudohypoparathyroidism if appropriately followed up. As obesity is a prominent feature of Albright hereditary osteodystrophy, such patients might seek bariatric surgery. After a Roux-en-Y gastric bypass, patients with Albright hereditary osteodystrophy associated with pseudopseudohypoparathyroidism need long-term follow-up on nutritional and metabolic issues.
- Published
- 2013
34. Pseudohypoparathyroidism in Children
- Author
-
Benjamin U. Nwosu
- Subjects
musculoskeletal diseases ,Albright hereditary osteodystrophy ,Pediatrics ,medicine.medical_specialty ,Genetic syndromes ,business.industry ,Exogenous obesity ,medicine ,Pseudohypoparathyroidism Type 1a ,business ,medicine.disease ,Pseudohypoparathyroidism - Abstract
Albright hereditary osteodystrophy (AHO) is a genetic syndrome characterized by a distinctive set of developmental and skeletal defects that may easily be misdiagnosed as exogenous obesity in children. There are very few publications detailing the comprehensive management of children and adolescents with this disorder. This chapter provides a comprehensive discussion of the various aspects of this disorder. At the end, the reader should be able to: (1) List the clinical features of Albright hereditary osteodystrophy, (2) Identify the genetic and molecular abnormalities of AHO, (3) List the clinical features of pseudohypoparathyroidism type 1a (PHP 1a), (4) Describe the management of children and adolescents with PHP 1a.
- Published
- 2011
35. Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy)
- Author
-
Daniel A. Doyle
- Subjects
Albright hereditary osteodystrophy ,medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,medicine.disease ,business ,Pseudohypoparathyroidism - Published
- 2011
36. Albright hereditary osteodystrophy: a rare case report
- Author
-
A Singh, Mridula Goswami, Gyanendra Kumar, Mahesh Verma, and H Grewal
- Subjects
medicine.medical_specialty ,Pediatrics ,Adolescent ,hypocalcaemia ,pseudopseudohypoparathyrodism ,Osteoporosis ,Parathyroid hormone ,Thyrotropin ,Malocclusion, Angle Class II ,Fibrous Dysplasia, Polyostotic ,Short stature ,Hyperphosphatemia ,Internal medicine ,medicine ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Hypocalcaemia ,Albright hereditary osteodystrophy ,General Dentistry ,Pseudohypoparathyroidism ,Hypocalcemia ,business.industry ,Tooth Abnormalities ,stimulatory guanine nucleotide binding regulatory protein (Gs-alpha activity) ,Fibrous dysplasia ,Metabolic disorder ,pseudohypoparathyroidism ,Open Bite ,medicine.disease ,lcsh:RK1-715 ,Thyroxine ,Endocrinology ,lcsh:Dentistry ,Pseudopseudohypoparathyroidism ,Female ,medicine.symptom ,business - Abstract
Albright hereditary osteodystrophy (AHO) is a rare hereditary metabolic disorder that may be associated with or without resistant to parathyroid hormone (pseudohypoparathyroidism). It is commonly characterized by a constellation of physical features of short stature, round face, short neck, and small metacarpals and metatarsals, mild mental retardation, osteoporosis, subcutaneous calcification, and sometimes olfactory and hearing functional defect. Hypocalcaemia and hyperphosphatemia are the most important manifestations of the case. We report a clinical case of siblings with AHO with reduced Gs-alpha activity and we discuss their clinical features with oral manifestations, radiographic findings, laboratory tests along with treatment.
- Published
- 2009
37. Albright Hereditary Osteodystrophy, Pseudohypoparathyroidism, and Other GNAS-Associated Syndromes
- Author
-
Louise C. Wilson
- Subjects
Albright hereditary osteodystrophy ,medicine.medical_specialty ,Endocrinology ,biology ,business.industry ,Internal medicine ,medicine ,GNAS complex locus ,biology.protein ,medicine.disease ,business ,Pseudohypoparathyroidism - Published
- 2009
38. Genetic Obesity Syndromes
- Author
-
Philip L. Beales and Anthony P. Goldstone
- Subjects
Albright hereditary osteodystrophy ,Genetics ,Cohen syndrome ,Feeding behavior ,Bardet–Biedl syndrome ,medicine ,macromolecular substances ,Gene deletion ,Biology ,medicine.disease ,Obesity ,Phenotype ,Alström syndrome - Abstract
There are numerous reports of multi-system genetic disorders with obesity. Many have a characteristic presentation and several, an overlapping phenotype indicating the likelihood of a shared common u
- Published
- 2008
39. A Case ofGNAS1Mutation in Pseudohypoparathyroidism Type Ia
- Author
-
Eun Sun Lee, Geon Park, Seung Hwa Rhie, Ji Hee Kim, and Se Eung Noh
- Subjects
medicine.medical_specialty ,biology ,business.industry ,medicine.disease ,Albright hereditary osteodystrophy ,Endocrinology ,Internal medicine ,Mutation (genetic algorithm) ,medicine ,GNAS complex locus ,biology.protein ,Pseudohypoparathyroidism type Ia ,Missense mutation ,business ,Pseudohypoparathyroidism - Abstract
가성부갑상선기능저하증은 신장의 부갑상선 호르몬에 대한 반응저하를 유발하는 유전질환이다. 가성부갑상선기능저하증 Ia형에서 다양한 GNAS 복합부위의 결손들이 발견되었으며, GNS1 유전자 돌연변이는 Gsα 단백 활성도를 감소시킨다. 대부분의 가성부갑상선기능저하증 Ia형 환자는 특징적으로 알브라이트 유전성 골이영양증(Albright hereditary osteodystrophy)과 저칼슘혈증, 부갑상선호르몬의 증가, Gsα 단백이 매개하는 여러 호르몬들에 대한 저항성을 보인다. 알브라이트 유전성 골이영양증은 작은 신장, 비만, 둥근얼굴형, 피하 석회결절 그리고 발과 손의 단지증 등의 다양한 증상이 발현되는 증후군이다. 저자들은 알브라이트 유전성 골이영양증, 근강축, 어지러움, 빛에 대한 과민성과 시력저하, 인지 및 운동기능의 장애를 보이는 47세 여자환자에서 직접염기서열분석을 통해 국내에서는 최초로 GNAS1 유전자 엑손 6에서 과오돌연변이(c.466G>A,p.Asp156Asn)를 증명하여 가성부갑상선기능저하증 Ia형으로 진단한 증례를 경험하였기에 보고하는 바이다.
- Published
- 2015
40. Characteristic Height Growth Pattern in Patients with Pseudohypoparathyroidism: Comparison between Type 1a and Type 1b
- Author
-
Y Sato, Setsuo Ota, Kaori Kinoshita, Yoichi Kohno, K Shimohashi, Masanori Minagawa, Michiko Anzai, and Itsuro Kazukawa
- Subjects
medicine.medical_specialty ,puberty ,business.industry ,Endocrinology, Diabetes and Metabolism ,growth ,Metabolic disorder ,pseudohypoparathyroidism ,Parathyroid hormone ,medicine.disease ,Short stature ,Adult height ,Albright hereditary osteodystrophy ,Endocrinology ,Male patient ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,In patient ,Original Article ,medicine.symptom ,business ,Pseudohypoparathyroidism ,height - Abstract
Pseudohypoparathyroidism (PHP) is a metabolic disorder characterized by organ resistance to the action of parathyroid hormone. PHP type 1 is subclassified into two apparent disorders, type 1a (PHP1a) and type 1b (PHP1b). Patients with PHP1a show Albright hereditary osteodystrophy including short stature. Patients with PHP1b have no such skeletal defects, however, literature regarding the growth of PHP1b is not currently available. We evaluated growth charts of PHP patients, including four PHP1a patients and six PHP1b patients. Growth patterns were different between PHP type 1a and 1b. Adult height was abnormally low in all PHP1a patients. The growth pattern of PHP1a was characterized by mild growth impairment in the prepubertal period, a blunted growth spurt and premature cessation of the growth spurt. The adult height of male PHP1b was slightly lower than average. An early growth spurt was observed only in male patients with PHP1b and it may reduce the adult height of male patients with PHP1b. This warrants further investigation into the growth and pubertal development of PHP1b patients.
- Published
- 2006
41. Molecular analysis of the GNAS1 gene for the correct diagnosis of Albright hereditary osteodystrophy and pseudohypoparathyroidism
- Author
-
Damiano Romagnolo, Martina Olivero, Fabio Buzi, Giuseppe Scirè, Roberto Lala, Luisa De Sanctis, F. Rigon, Irma Dianzani, Giampiero I. Baroncelli, Carlo De Sanctis, Mohamad Maghnie, Marco Cappa, Mariacarolina Salerno, Salvatore Grosso, Salvatore Di Maio, Antonino Crinò, L., DE SANCTIS, D., Romagnolo, M., Oliviero, F., Buzi, M., Maghnie, G., Scire, A., Crino, Baroncelli, G. I., Salerno, Mariacarolina, S., DI MAIO, M., Cappa, S., Grosso, F., Rigon, R., Lala, C., DE SANCTIS, and I., Dianzani
- Subjects
Adult ,Male ,musculoskeletal diseases ,Adolescent ,endocrine system diseases ,Molecular analysis,GNAS1 gene, Albright hereditary osteodystrophy, pseudohypoparathyroidism ,DNA Mutational Analysis ,Mutation, Missense ,Biology ,Fibrous Dysplasia, Polyostotic ,Albright hereditary osteodystrophy ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,medicine ,GNAS complex locus ,Humans ,Child ,Gene ,Pseudohypoparathyroidism ,Genetics ,medicine.disease ,Molecular analysis ,body regions ,Phenotype ,Codon, Nonsense ,Recien nacido ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female - Abstract
Pseudohypoparathyroidism (PHP) is a heterogeneous disease characterized by PTH resistance and classified as types Ia, Ib, Ic, and II, according to its different pathogenesis and phenotype. PHP-Ia patients show Gsalpha protein deficiency, PTH resistance, and typical Albright hereditary osteodystrophy (AHO). Heterozygous mutations in the GNAS1 gene encoding the Gsalpha protein have been identified both in PHP-Ia and in pseudopseudohypoparathyroidism (PPHP), a disorder with isolated AHO. A single GNAS1 mutation may be responsible for both PHP-Ia and PPHP in the same family when inherited from the maternal and the paternal allele, respectively, suggesting that GNAS1 is an imprinted gene. To evaluate whether molecular diagnosis is a useful tool to characterize AHO and PHP when testing for Gsalpha activity and PTH resistance is not available, we have performed GNAS1 mutational analysis in 43 patients with PTH resistance and/or AHO. Sequencing of the whole coding region of the GNAS1 gene identified 11 mutations in 18 PHP patients, eight of which have not been reported previously. Inheritance was ascertained in 13 cases, all of whom had PHP-Ia: the mutated alleles were inherited from the mothers, who had AHO (PPHP), consistent with the proposed imprinting mechanism. GNAS1 molecular analysis confirmed the diagnosis of PHP-Ia and PPHP in the mutated patients. Our results stress the usefulness of this approach to obtain a complete diagnosis, expand the GNAS1 mutation spectrum, and illustrate the wide mutation heterogeneity of PHP and PHP-Ia.
- Published
- 2003
42. Albright Hereditary Osteodystrophy, Pseudohypoparathyroidism, and Gs Deficiency
- Author
-
Lee S. Weinstein
- Subjects
musculoskeletal diseases ,endocrine system ,medicine.medical_specialty ,business.industry ,Osteitis fibrosa cystica ,Parathyroid hormone ,medicine.disease ,Albright hereditary osteodystrophy ,Hyperphosphatemia ,Normal renal function ,Endocrinology ,Internal medicine ,medicine ,natural sciences ,business ,hormones, hormone substitutes, and hormone antagonists ,Pseudohypoparathyroidism ,Primary Hypoparathyroidism ,Hormone - Abstract
Pseudohypoparathyroidism (PHP) is a term that refers to a heterogeneous group of metabolic disorders in which resistance to parathyroid hormone (PTH), characterized by hypocalcemia, hyperphosphatemia, and elevation of serum PTH in the setting of normal renal function, is the major clinical feature. In the original report by Fuller Albright, PHP patients showed reduced calcemic and phosphaturic responses to injected bovine parathyroid extract compared to patients with primary hypoparathyroidism (1). This observation led to the speculation that PHP is caused by a defect in PTH action within its target tissues, and was the first description of a hormone resistance syndrome. Subsequent studies describing parathyroid hyperplasia and elevation of immunoreactive serum PTH in untreated PHP patients confirmed that PTH resistance was the underlying defect (2,3).
- Published
- 1998
43. Osteoma cutis as a presenting sign of pseudohypoparathyroidism
- Author
-
Craig B. Langman, Susan B. Mallory, Anne W. Lucky, Zulf Mughal, Francis B. Mimouni, and Julie S. Prendiville
- Subjects
Male ,medicine.medical_specialty ,Skin Neoplasms ,endocrine system diseases ,Cutis ,Dermatology ,Albright hereditary osteodystrophy ,medicine ,Humans ,Osteoma cutis ,Family history ,Osteoma ,Pseudohypoparathyroidism ,business.industry ,Infant ,medicine.disease ,Osteochondrodysplasia ,Surgery ,body regions ,Pediatrics, Perinatology and Child Health ,Pseudopseudohypoparathyroidism ,Female ,business - Abstract
Four unrelated children with oosteoma cutis and Albright hereditary osteodystrophy (pseudohypoparathyroidism and pseudopseudohypoparathyroidism) are described. All four patients were normocalcemic when they were first seen with cutaneous ossification. A diagnosis of Albright hereditary osteodystrophy was established on the basis of associated somatic features, radiographic abnormalities, and family history. Progression to pseudohypoparathyroidism was documented in two children who developed hypocalcemia at 2 and 3 years of age, respectively. Early recognition of the skin manifestations of this syndrome and careful follow-up are important to prevent the deleterious effects of hypocalcemia. Osteoma cutis is a common sign of Albright hereditary osteodystrophy in infancy and childhood, and its significance should not be overlooked, even in the normocalcemic patient.
- Published
- 1992
44. Growing Fat with Mom's Help
- Author
-
L. B. Ray
- Subjects
Α subunit ,medicine.medical_specialty ,Multidisciplinary ,Guanine ,Disease ,Biology ,medicine.disease ,Obesity ,Albright hereditary osteodystrophy ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,chemistry ,Hormone receptor ,Internal medicine ,Mutation (genetic algorithm) ,medicine - Abstract
Physiology A mutation in the α subunit of the guanine nucleotide–binding protein Gs, which transduces signals from various hormone receptors, causes obesity and insulin resistance in the human disorder Albright hereditary osteodystrophy. These disease manifestations occur in individuals with
- Published
- 2009
45. A deletion hot-spot in exon 7 of the G8α gene (GNAS1) in patients with Aibright hereditary osteodystrophy
- Author
-
Louise C. Wilson, Kathryn A. Wilson, Bryan E. Hainline, Richard C. Trembath, Lee S. Weinstein, Dawen Yu, Jacob L. Brener, Monique E. Oude-Luttikhuis, and Shuhua Yu
- Subjects
medicine.medical_specialty ,Hot spot (veterinary medicine) ,General Medicine ,Biology ,medicine.disease ,Osteochondrodysplasia ,Albright hereditary osteodystrophy ,Exon ,Endocrinology ,Internal medicine ,Genetics ,medicine ,GNAS complex locus ,biology.protein ,In patient ,Molecular Biology ,Gene ,Genetics (clinical) ,Pseudohypoparathyroidism - Published
- 1995
46. Evidence of Genomic Imprinting of Pseudohypoparathyroidism in a Family with Albright Hereditary Osteodystrophy ♦ 745
- Author
-
Patricia A Galvin-Parton and Konstantin L Zakashanskiy
- Subjects
musculoskeletal diseases ,Genetics ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,medicine.disease ,body regions ,Albright hereditary osteodystrophy ,Endocrinology ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,business ,Genomic imprinting ,Pseudohypoparathyroidism - Abstract
Evidence of Genomic Imprinting of Pseudohypoparathyroidism in a Family with Albright Hereditary Osteodystrophy ♦ 745
- Published
- 1998
47. Picture of the Month
- Author
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Tunnessen Ww, Eroglu Y, and Bober E
- Subjects
Transient Primary Hypothyroidism ,medicine.medical_specialty ,Pediatrics ,medicine.diagnostic_test ,business.industry ,Brachydactyly ,Nutritional status ,medicine.disease ,Thyroid function tests ,Infant newborn ,Surgery ,Albright hereditary osteodystrophy ,Recien nacido ,Pediatrics, Perinatology and Child Health ,medicine ,Syndactyly ,business - Published
- 1997
48. Genetic and epigenetic alterations in the GNAS locus and clinical consequences in Pseudohypoparathyroidism: Italian common healthcare pathways adoption
- Author
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De Sanctis L., Giachero F., Mantovani G., Weber G., Salerno M., Baroncelli G. I., Elli M. F., Matarazzo P., Wasniewska M., Mazzanti L., Scirè G., Tessaris D, Study Group Endocrine diseases due to altered function of Gsα protein of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), De Sanctis, L, Giachero, F., Mantovani, G., Weber, G., Salerno, M., Baroncelli, G. I., Elli, M. F., Matarazzo, P., Wasniewska, M., Mazzanti, Laura, Scirè, G., Tessaris, D., Weber, Giovanna, Mazzanti, L., De Sanctis, L., Tessaris, D, and Study Group Endocrine diseases due to altered function of Gsα protein of the Italian Society of Pediatric Endocrinology and Diabetology, (ISPED)
- Subjects
0301 basic medicine ,Male ,Disease ,Bioinformatics ,Pediatrics ,Epigenesis, Genetic ,0302 clinical medicine ,GTP-Binding Protein alpha Subunits, Gs ,Medicine ,Osteodystrophy ,Child ,biology ,GNAS locu ,Albright Hereditary Osteodystrophy ,Perinatology and Child Health ,Chromogranin ,Italy ,GTP-Binding Protein alpha Subunits, G ,Pseudohypoparathyroidism ,Child, Preschool ,Female ,Human ,medicine.medical_specialty ,GNAS gene ,GNAS locus ,PTH resistance ,Pediatric endocrinology ,030209 endocrinology & metabolism ,Locus (genetics) ,03 medical and health sciences ,Internal medicine ,GNAS complex locus ,Chromogranins ,Humans ,Epigenetics ,Settore MED/38 - Pediatria Generale e Specialistica ,business.industry ,Research ,Brachydactyly ,Pediatrics, Perinatology and Child Health ,Infant ,medicine.disease ,030104 developmental biology ,Endocrinology ,Mutation ,biology.protein ,business - Abstract
BACKGROUND: Genetic and epigenetic alterations in the GNAS locus are responsible for the Gsα protein dysfunctions causing Pseudohypoparathyroidism (PHP) type Ia/c and Ib, respectively. For these heterogeneous diseases characterized by multiple hormone resistances and Albright's Hereditary Osteodystrophy (AHO) the current classification results inadequate because of the clinical overlap between molecular subtypes and a standard clinical approach is still missing. In the present paper several members of the Study Group Endocrine diseases due to altered function of Gsα protein of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) have reviewed and updated the clinical-molecular data of the largest case series of (epi)/genetically characterized AHO/PHP patients; they then produced a common healthcare pathway for patients with these disorders. METHODS: The molecular analysis of the GNAS gene and locus identified the causal alteration in 74 subjects (46 genetic and 28 epigenetic mutations). The clinical data at the diagnosis and their evolution during up to 15 years follow-up were collected using two different cards. RESULTS: In patients with genetic mutations the growth impairment worsen during the time, while obesity prevalence decreases; subcutaneous ossifications seem specific for this group. Brachydactyly has been detected in half of the subjects with epigenetic alterations, in which the disease overts later in life, often with symptomatic hypocalcaemia, and also early TSH and GHRH resistances have been recorded. CONCLUSIONS: A dedicated healthcare pathway addressing all these aspects in a systematic way would improve the clinical management, allowing an earlier recognition of some PHP features, the optimization of their medical treatment and a better clinical-oriented molecular analysis. Furthermore, standardized follow-up data would provide new insight into less known aspects.
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