Search

There is a lack of highly reliable tools evaluating healthcare professionals’ competences on Pediatric Palliative Care (PPC) and Pain Therapy (PT). The aim of this study is to document the development of an online questionnaire to assess Perceived, Wished and Actual Knowledge of healthcare workers on PPC/PT. The tool was built on the basis of the Italian Society for Palliative Care PPC Core Curriculum (CC) for physicians, nurses and psychologists. Face validity, internal consistency and the underlying structure were evaluated after a field testing in a referral hospital, Friuli-Venezia Giulia, Italy. One hundred five respondents completed the questionnaire. High internal consistency for both scales of Perceived and Wished Knowledge was found (α = 0.95 and α = 0.94, respectively). Psychologists reported higher levels of self-Perceived skills on the psychosocial needs of the child and family at the end of life (p = 0.006), mourning (p = 0.003) and ethics and deontology in PT/PC (p = 0.049). Moreover, when Actual Knowledge was tested, they also provided the highest number of correct answers (p = 0.022). No differences were found by profession for Wished Knowledge. The questionnaire showed promising psychometric properties. Our findings suggest the need of continuous training in this field and identify contents to be addressed in future training programs.

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: −0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.

Background Mitochondrial diseases (MDs) are systemic disorders that can affect multiple organs. Renal manifestations, including renal tubular acidosis, are common because kidneys are particularly vulnerable to energy deprivation. Treatment of MDs is often complex and electrolyte replacement can be difficult especially in pediatric patients, because large and repeated amounts of oral supplements are needed but are not well tolerated.Case presentation We describe the case of a girl affected by Kearns-Sayre disease with severe renal tubular acidosis. The management of her metabolic acidosis was challenging because she showed persistent low levels of serum bicarbonates despite a progressive incrementation of oral bicarbonates. Furthermore, as a result to the ingestion of large amounts of alkali, the girl developed an aversion to oral supplementation. After positioning a percutaneous gastrostomy (PEG) and starting enteral administration of bicarbonates (with daily boluses and continuous nocturnal infusion), she finally obtained an adequate electrolyte control, with a significant increase in her quality of life.Conclusions In MDs, the combination of nocturnal continuous enteral administration of alkali plus diurnal boluses may represent a valid solution to correct metabolic acidosis. It can also result in an improved patients’ quality of life, particularly in pediatric settings, where compliance to oral therapy is often lacking due to the large and repeated amounts of unpalatable bicarbonates solutions required.

Tetralogy of Fallot (ToF) can be associated with a wide range of extracardiac anomalies, with an underlying etiology identified in approximately 10% of cases. Individuals affected with Myhre syndrome due to recurrent SMAD4 mutations frequently have cardiovascular anomalies, including congenital heart defects. In addition to two patients in the literature with ToF, we describe five additional individuals with Myhre syndrome and classic ToF, ToF with pulmonary atresia and multiple aorto-pulmonary collaterals, and ToF with absent pulmonary valve. Aorta hypoplasia was documented in one patient and suspected in another two. In half of these individuals, postoperative cardiac dysfunction was thought to be more severe than classic postoperative ToF repair. There may be an increase in right ventricular pressure, and right ventricular dysfunction due to free pulmonic regurgitation. Noncardiac developmental abnormalities in our series and the literature, including corectopia, heterochromia iridis, and congenital miosis suggest an underlying defect of neural crest cell migration in Myhre syndrome. We advise clinicians that Myhre syndrome should be considered in the genetic evaluation of a child with ToF, short stature, unusual facial features, and developmental delay, as these children may be at risk for increased postoperative morbidity. Additional research is needed to investigate the hypothesis that postoperative hemodynamics in these patients may be consistent with restrictive myocardial physiology.

Background. There is a lack of validated tools to evaluate the healthcare professionals’ competences on Pediatric Palliative Care (PPC) and Pain Therapy (PT). The aim of this study is to document the development and validation of a questionnaire to assess perceived, wished and actual knowledge of healthcare workers on PPC/PT. Methods. On the basis of the Italian Society for Palliative Care PPC Core Curriculum (CC) for physicians, nurses and psychologists, an online questionnaire was developed in four sequential steps. Construct validity, coherence of the instrument, and educational needs of participants were assessed after a field testing in a referral hospital, Northeast Italy. Results. One-hundred-five respondents completed the online questionnaire, from January 1st to July 31th 2019. Findings showed high internal consistency for both scales of perceived and wished knowledge (⍺=0.95 and ⍺=0.94, respectively). Psychologists reported higher levels of self-perceived skills on psychosocial needs of child and family at the end of life (p=0.006), mourning (p=0.003) and ethics and deontology in PT/PC (p=0.049). No differences were found by profession in terms of wished knowledge. Regarding actual knowledge assessment psychologists provided the bigger number of correct answers (p=0.022). Conclusions. The questionnaire showed promising psychometric properties as a multidisciplinary instrument to measure health professionals’ knowledge on PPC/PT. Our findings suggest a need of continuous training in this topic and present possible content to be addressed by decision makers when organizing future training programs and/or educational events.

Background: Plexiform neurofibromas are benign neoplasms that develop in 20-50% children with neurofibromatosis type 1 (NF1). Selumetinib was approved as treatment for symptomatic and inoperable plexiform neurofibromas. Subclinical left ventricular ejection fraction reduction is a less common effect of selumetinib. Objective: We aimed to investigate the contractile function of the heart in a cohort of children with NF1 treated with selumetinib. Methods: We designed a cross-sectional study including 17 patients with NF1 who received selumetinib. Echocardiographic parameters were compared with a cohort of 17 healthy children matched by sex and age and another group of 17 children with untreated NF1. Results: Compared with healthy controls, patients with NF1 treated with selumetinib had lower mean values of global longitudinal strain (- 22.9 ± 2% vs -25.5 ± 2%; p = 0.001), fractional shortening (36 ± 4% vs 43 ± 8%; p = 0.02) and tricuspid annular plane systolic excursion (19 ± 3 mm vs 23 ± 2 mm; p = 0.001); no difference was found in left ventricular ejection fraction (63 ± 4% vs 65 ± 3%; p = 0.2 respectively). Median treatment time with selumetinib at the time of the echocardiographic evaluation was 22 ± 16 months. Conclusions: Patients with NF1 treated with selumetinib may experience subtle changes in systolic function identified by global longitudinal strain and not revealed by left ventricular ejection fraction. Global longitudinal strain might be useful to monitor cardiac function in this cohort of patients for the duration of therapy.

Type I interferonopathies are autoinflammatory monogenic disorders arising from excessive production of interferons. Some manifestations like chilblains, neurologic involvement, arthritis and lipodystrophy may be shared by several diseases. Measure of interferon score and genetic analysis can assist a definite diagnosis. Among immunomodulant drugs, glucocorticoids, micofenolate and antimalarials can be of some benefit, however other drugs like JAK inhibitors seem more effective in controlling interferon-related complaints. Apart from allowing better diagnosis and care to affected patients, the study of interferonopathies may also reflect on a better knowledge on multifactorial disorders associated with interferon-related inflammation.

Mouhamed, a 7-year-old boy of African origin, presented with progressive fatigue and difficulty in walking. He was never treated with vitamin D supplementation. The evaluation of his calcium-phosphorus metabolism revealed a myopathy related to severe rickets. Therefore, he was treated with high-dose vitamin D3 and myopathy and fatigue progressively resolved. Vitamin D plays a crucial role in the calcium-phosphorus metabolism, by acting on enterocytes, osteoclasts and renal tubule. Vitamin D deficiency is defined when the 25OHD value is less than 20 ng/ml. In order to guarantee the assumption of the minimum daily dose of vitamin D, it is recommended to start vitamin D3 supplementation in all newborns and infants in their first year of life, regardless of the feeding modality. Exposure to the sun is essential for the activation of vitamin D, so dark-skinned children and mothers or those little exposed to the sun should start vitamin D3 supplementation. Vitamin D3 should also be supplemented in children with cerebral palsy and in patients treated with anti-epileptic drugs. Other conditions at risk of vitamin D deficiency are inflammatory bowel disease, celiac disease, cystic fibrosis, obesity, liver failure, cholestasis and vegetarian or vegan diets. Classic signs of rickets are the rickety rosary, the widening of the wrist and the arching of the tibia. Severe hypocalcaemia secondary to vitamin D deficiency can occur with dilated cardiomyopathy or convulsions, especially in dark-skinned infants. Vitamin D deficiency should be considered in children with progressive myopathy or muscular weakness, especially in dark-skinned ones or in those poorly exposed to the sun for cultural or religious reasons.

Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p.(Asp248Glu)] in the highly-conserved motor domain of KIF1A. In addition, three individuals with severe neurodevelopmental disorder along with clinical features overlapping with KAND are also reported carrying de novo heterozygous novel [NP_001230937.1:p.(Cys92Arg) & p.(Pro305Leu)] or previously reported [NP_001230937.1:p.(Thr99Met)] variants in KIF1A. In silico tools predicted these variants to be likely pathogenic, and 3D molecular modelling predicted defective ATP hydrolysis and/or microtubule binding. Using the neurite tip accumulation assay, we demonstrated that all novel KIF1A variants significantly reduced the ability of the motor domain of KIF1A to accumulate along neurite lengths of differentiated SH-SY5Y cells. In vitro microtubule gliding assays showed significantly reduced velocities for the variant p.(Asp248Glu) and reduced microtubule binding for the p.(Cys92Arg) and p.(Pro305Leu) variants, suggesting decreased ability of KIF1A to move along microtubules. Thus, this study further expanded the phenotypic characteristics of KAND individuals with pathogenic variants in KIF1A motor domain to include clinical features commonly seen in RTT individuals. This article is protected by copyright. All rights reserved.

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide, and lifestyle modification is the current standard treatment. The aim of the study was to estimate the effect of two different physical activity (PA) programs, a Low Glycemic Index Mediterranean Diet (LGIMD), and their combined effect on the NAFLD score as measured by FibroScan&reg, Methods: Moderate or severe NAFLD subjects (n = 144) were randomly assigned to six intervention arms during three months. Interventions arms were a control diet, LGIMD, aerobic activity program (PA1), combined activity program (PA2), and LGIMD plus PA1 or LGIMD plus PA2. The data were compared at baseline, at 45 days, and at 90 days. Analysis of variance was performed under the intention-to-treat principle. Results: There was a statistically significant reduction in the NAFLD score after 45 days of treatment in every working arm except for Arm 1 (control diet). After 90 days, the best results were shown by the intervention arms in which LGIMD was associated with PA: LGIMD plus PA1 (&minus, 61.56 95% C.I. &minus, 89.61, &minus, 33.50) and LGIMD plus PA2 (&minus, 38.15 95% C.I &minus, 64.53, &minus, 11.77). Conclusion: All treatments were effective to reduce NAFLD scores, but LGIMD plus PA1 was the most efficient.

A 3-month-old male infant was evaluated for the persistence of erythema toxicum neonatorum. Physical examination was remarkable for a papulopustular rash on his hands and feet, with similar lesions on his trunk. The baby was irritable and continuously rubbed his soles. The parents as well presented similar cutaneous lesions, which had been treated with anti-histamine drugs without effect. The suspect of scabies was therefore raised and eventually confirmed by the examination of the skin scraping sample, showing the presence of the mites. In both the infant and his parents the clinical picture resolved after two cycles of topical permethrin. In the neonatal age, scabies can act as a great mimicker. In front of any pruritic rash, it is therefore mandatory to search for affected relatives. In fact a prompt diagnosis is crucial to prevent the superinfection of the patient lesions, as well as epidemic outbreaks.

Background Plexiform neurofibromas (PNs) are congenital tumors that affect around 50 % of the subjects with neurofibromatosis type 1. Despite being histologically benign, PNs can grow rapidly, especially in the pediatric age, and cause severe morbidities. In the past, various therapeutic approaches have been proposed to treat these masses, none of which obtained valuable results. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. The drug’s most common side effects, which usually are mild or moderate, include gastrointestinal symptoms (diarrhea, abdominal pain), dermatologic manifestations (maculo-papular and acneiform rash, paronychia, mucositis), and various laboratory test abnormalities (elevation of creatine kinase and aminotransferase). Cases presentation We report two previously undescribed adverse events in pediatric patients: peripheral edema and hair color change. The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). The edema involved the right leg, and the patient did not complain of pain. The second case of peripheral edema occurred in a 12-year-old girl after six months of therapy with selumetinib at the standard dose, involving her lower left leg. The patient initially complained of pain in that area, but it gradually and spontaneously resolved. In both patients, all the radiological exams, including lymphoscintigraphy, pelvic and abdominal ultrasound, and doppler ultrasound of the affected limb, as well as blood tests, revealed no abnormalities. Hair color change appeared in a 4-year-old boy after six months of therapy at the standard dose. The boy’s hair, whose natural color was dark blonde, became lighter in some areas. Despite the appearance of these side effects, all the patients and their families decided to continue the treatment with selumetinib, in considerations of its clinical benefits. Conclusions Since the use of selumetinib to treat plexiform neurofibromas is increasing in the pediatric population, clinicians should be aware of its side effects, so to decide whether continuing the treatment, reducing the dose or even interrupting it, when appropriate.

MED13-related disorder is a new neurodevelopmental disorder recently described in literature, which belongs to the group of CDK8-kinase module genes-associated conditions. It is characterized by variable intellectual disability and/or developmental delays, especially in language. Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), eye or vision problems, hypotonia, mild congenital hearth abnormalities and dysmorphisms have been described among individuals with MED13 mutations. We report the case of a 13-year-old girl who received a previous clinical diagnosis of Kabuki syndrome (KS) without mutations in classic KS genes. After a whole exome sequencing (WES) analysis a de novo missense mutation in MED13 (c.C979T; p.Pro327Ser) was found. This variant has been once described in literature as accountable for a novel neurodevelopmental disorder. The aim of this report is to improve clinical delineation of MED13-related condition and to explore differences and similarities between KS spectrum and MED13-related disorders.

N/A

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%–11.2% (reference value 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder.

N/A

Background: Homocystinuria is a rare inborn error of metabolism, resulting in the accumulation of homocysteine and methionine in tissues, which manifests as disorders of the connective tissues and increased risk of thromboembolism. The latter is the primary cause of morbidity and mortality, and can be prevented by the prompt start of the specific therapy aimed at lowering homocysteine plasma levels.Case presentation: A nine-year-old boy was admitted to the Emergency Department for a severe headache associated with torticollis, dysarthria, difficulty in walking and extreme irritability. His past medical history was relevant for bilateral lens ectopia and epilepsy, associated with a “marfanoid habitus”. A brain CT scan was consistent with cerebral venous thrombosis. The association between the marfanoid habitus and the thromboembolic event raised the suspicion of homocystinuria, which was eventually confirmed by the high levels of serum homocysteine, and the genetic testing. Anticoagulation therapy was started, together with pyridoxine and folate, and eventually betaine and dietary protein restriction, with a consequent satisfactory fall in homocysteine levels, along with clinical recovery.Conclusions: This case enhances the importance of dosing serum homocysteine in every child investigated for a marfanoid habitus, given the impact of the early diagnosis and treatment in the prevention of thromboembolic events.

Background: Plexiform neurofibromas (PN) are congenital tumors that affect up to 50% of individuals with neurofibromatosis type 1. Despite their benign nature, they can grow rapidly and cause severe morbidities. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, was reported to induce a clinical response in pediatric subjects with inoperable PN. Objective: The aim of this paper is to describe a prospective case series of patients treated with selumetinib with emphasis on drug adverse events. Patients and methods: All the subjects who received selumetinib at the Pediatric Department of Scientific Research Institute and Hospital “Burlo Garofolo”, from November 2017 to January 2020, were progressively included. We monitored the patients with a follow-up visit every 3 months. MRI or CT scans to monitor the growth of the tumor were performed after 3 months of treatment, and then every 6–9 months. Results: Selumetinib was prescribed to nine children, with a total of 17 inoperable PN. The mean follow-up period was 12 months. During the follow-up, one patient experienced an ischemic stroke, unrelated to the treatment. Only minor adverse events were observed: six individuals developed gastrointestinal side effects, seven patients presented a mild form of acne, six had paronychia, four developed irritability, and two showed a mild increase in creatine kinase. None of the patients stopped the treatment. Tumor reduction > 20% was recorded in 16 out of 17 PN (94%). One PN remained stable. No tumor growth was recorded during the treatment. Conclusions: In this case series, selumetinib appears to be effective and safe for the pediatric population.

not available

The authors present the case of a girl diagnosed with spinal muscular atrophy (SMA) and discuss how the new therapeutic approaches may change the prospect of life of the affected patients.

N/A

Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [ 1 ]. The disease is typically expressed when fructose- and sucrose-containing foods are first introduced in the diet; acute manifestations include nausea, vomiting, abdominal distress, and symptomatic hypoglycemia [ 1 , 2 ]. Chronic fructose ingestion eventually leads to poor feeding, growth retardation and gradual liver and/or renal failure [ 3 , 4 ]. Some patients may remain undiagnosed until adulthood because of a self-protective avoidance of sweet tasting food that prevents the development of acute toxicity from fructose containing food; however, these subjects may suffer intermittent symptoms throughout life, leading to potentially serious misdiagnosis [ 4 ]. We report the case of a patient with unrecognized hereditary fructose intolerance in which chronic gastrointestinal complaints, low body weight, and unexplained food avoidance were addressed as manifestations of an eating disorder during adolescence.

With the development of precision medicines based on small molecules, antibodies, RNAs and gene therapy, technological innovation is providing some exciting possibilities to treat the most severe genetic diseases. However, these treatments do not always lead to a cure for the disease, and there are several factors that may hinder their overall success. Patients living during a period of great medical change and innovation may benefit from these technological advances but may also just face failures, both in terms of frustrated hopes as well as suffering. In this article, we are telling the stories of three children with rare and severe disorders, who live in an age of significant medical changes, bearing the burden of difficult scientific and ethical choices. The first two cases that are suffering respectively from severe immunodeficiency and beta thalassemia have already been described in scientific journals, as well as in popular magazines. Although similar when considering the medical challenges, the two cases had opposite outcomes, which resulted in distinct ethical implications. The third case is a baby with spinal muscular atrophy, living at a time of continued innovation in the treatment of the disease. With these cases, we discuss the challenges of providing correct information and proper counseling to families and patients that are making the bumpy journey on the road of medical innovation.

Background: Irisin, a hormone-like myokine, regulates energy homeostasis and mediates the benefits of physical activity on health. Methods: To estimate the effect of different diets on irisin concentrations in subjects with the Metabolic Syndrome (MetS). Methods: Subjects with MetS were derived from a population survey, 163 subjects were enrolled and randomized to a: Low Glycaemic Index (LGID), Mediterranean (MD) or Low Glycaemic Index Mediterranean (LGIMD) Diet, and the groups were compared, also with 80 controls without MetS. Sociodemographic, medical and nutritional data were collected and fasting blood samples drawn. Subjects underwent LUS and bioimpedentiometry. Generalized Estimating Equations were performed. Results: At baseline, lower irisin concentrations were observed in MetS subjects. Mean irisin levels increased in all diet groups but only the LGID group reached statistical significance, as well as showing an interaction between LGID and time at the sixth month examination (4.57, 95% CI &minus, 1.27, 7.87). There was a positive effect of Vegetable Proteins (0.03, 95% CI &minus, 0.01,0.06) and Saturated Fatty Acids (0.04, 95% CI 0.01, 0.07) on irisin concentrations. In the LGIMD, a positive effect on Fat-Free Mass (0.38, 95% CI 0.19, 0.57) and a negative effect on the Body Mass Index (&minus, 0.75, 95% CI &minus, 1.30, &minus, 0.19) were observed. Conclusions: There seems to be a link between diet and muscle physiology. We showed that patients following a LGID had higher levels of irisin, a promising biomarker of muscle activity.

A group of 608 apparently healthy patients, 136 men and 472 women, either overweight or obese, aged 18-69 years, were examined. BMI, waist circumference, fasting blood glucose (FBG), insulin, and complement 3 (C3) serum levels were measured; the homeostasis model assessment (HOMAIR) was used to evaluate insulin resistance; and physical activity was quantified by a questionnaire.HOMAIR showed a positive correlation with BMI (r: 0.478, p0.001), waist circumference (r: 0.487, p0.001), and C3 (r: 0.445, p0.001). Moreover, it was significantly associated with gender (F Fisher = 22.12, p0.001), and the mean HOMAIR levels were significantly different among the three groups of physical activity, with the lowest level of insulin resistance at the highest level of physical activity (F=7,31, p0.001). A multiple regression analysis was carried out with HOMAIR as the dependent variable and gender, age, BMI, waist circumference, C3 and the level of physical activity as independent variables (fitted model: F = 41.24, P0.001, R2 = 0.328). HOMAIR maintained an independent association with C3 (β = 0.678, P0.001), sex (β = 0.189, P0.001), BMI (β = 0.637, P0.01), and age (β = -0.004, P0.05).This study of a cohort of overweight and obese subjects has shown that insulin resistance (dependent variable) is positively associated with C3 serum levels, independently of age, gender, anthropometric parameters and physical activity, suggesting that higher C3 serum levels may directly increase insulin resistance in obesity.

Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (&plusmn, 10.18) with a mean BMI of 33.41 (&plusmn, 4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95&ndash, 0.99), chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34&ndash, 0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74&ndash, 0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01&ndash, 1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01&ndash, 1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01&ndash, 1.21), fats (O.R. 1.12, 95% C.I. 1.01&ndash, 1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.

A 10-year-old child was referred with bilateral curving and bending of the index fingers noted from birth. His previous history included astigmatism and left knee retraction resulting in flexion deformity since he was 3 years old. Paediatricians should consider distal arthrogryposis type 5D (DA5D) in children with a family history of clino-camptodactyly and articular retraction. His physical examination revealed clubfoot hypoplasia of the index fingers, adducted thumbs and …

Congenital hyperinsulinism (CHI) occurs as a consequence of unregulated insulin secretion from the pancreatic beta-cells. Severe recessive mutations and milder dominant mutations have been described in the ABCC8 and KCNJ11 genes encoding SUR1 and Kir6.2 subunits of the beta-cell ATP-sensitive K(+) channel. Here we report two patients with CHI unresponsive to medical therapy with diazoxide. Sequencing analysis identified a compound heterozygous mutation in ABCC8 in both patients. The first one is a carrier for the known mild dominant mutation p.Glu1506Lys jointly with the novel mutation p.Glu1323Lys. The second carries the p.Glu1323Lys mutation and a second novel mutation, p.Met1394Arg. Functional studies of both novel alleles showed reduced or null cell surface expression, typical of recessive mutations. Compound heterozygous mutations in congenital hyperinsulinism result in complex interactions. Studying these mechanisms can improve the knowledge of this disease and modify its therapy.

Background Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. Aim The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. Methods The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. Results Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic blood pressure when a multiple regression analyses was performed by considering osteocalcin levels as the dependent variable and BMI, systolic blood pressure, HbA1c, and HDL cholesterol as independent variables. When age was included in the analyses among the independent variables, osteocalcin levels maintained an independent association with BMI, systolic blood pressure, HbA1c, and HDL cholesterol, but not with age. Discussion and conclusion The results of the present study seem to suggest that patients with obesity and type 2 diabetes are at higher risk of lower osteocalcin levels and bone formation, whereas higher HDLcholesterol levels and systolic blood pressure seem to be associated to higher osteocalcin production.

A 4-year-old boy presented with macrocephaly, hypertelorism and broad forehead (figure 1). His 2-year-old sister and their mother also presented with macrocephaly without developmental delay. The mother had a history of numerous basal skin carcinomas from the age of 20 years and of odontogenic keratocysts since she was a child. All three showed palmoplantar pitting after …

Aim: To identify clinical and laboratory features that can drive the differential diagnosis of a primary immunodeficiency diseases in patients with ectodermal defects. Methods: Analysis of selected teaching cases. Results: We identified four exemplary cases that allowed to point out specific clues. Conclusions: A careful evaluation of immune and ectodermal signs is the key to the diagnosis. Therefore, a multidisciplinary approach can lead to diagnosis and to an appropriate treatment in most of the cases.

In this paper, is reported the identification of two chimeric patients, a rare finding if sexual abnormalities are absent. However, their chimeric condition is responsible at least for the Silver–Russell phenotype observed in one of the two patients. By single nucleotide polymorphism‐array analyses, it was possible to clearly define the mechanism responsible for this unusual finding, underlining the importance of this technique in bringing out the perhaps submerged world of chimeras.

A 8-month-old child was referred to our Dermatologic Unit for suspected Neurofibromatosis type 1 (NF 1), because of the appearance, since few days after birth, of numerous café-au-lait spots (seven larger than 5 mm); no other sign evocative of NF 1 was found. Her family history was remarkable for the presence of multiple café-au-lait spots in the mother, the grandfather and two aunts. The family had been already examined for NF 1, but no sign evocative of the disease was found. We then suspected Legius syndrome, a dominant disease characterized by a mild neurofibromatosis 1 phenotype. The diagnosis was confirmed by the finding of a mutation in SPRED1 gene, a feedback regulator of RAS/MAPK signaling. Here, we discuss the differential diagnosis of cafè-au-lait spots and we briefly review the existing literature about Legius syndrome.

Stickler syndrome (STL) is a clinically variable and genetically heterogeneous syndrome characterized by ophthalmic, articular, orofacial, and auditory manifestations. STL has been described with both autosomal dominant and recessive inheritance. The dominant form is caused by mutations of COL2A1 (STL 1, OMIM 108300), COL11A1 (STL 2, OMIM 604841), and COL11A2 (STL 3, OMIM 184840) genes, while recessive forms have been associated with mutations of COL9A1 (OMIM 120210) and COL9A2 (OMIM 120260) genes. Type IX collagen is a heterotrimeric molecule formed by three genetically distinct chains: α1, α2, and α3 encoded by the COL9A1, COL9A2, and COL9A3 genes. Up to this time, only heterozygous mutations of COL9A3 gene have been reported in human and related to: (1) multiple epiphyseal dysplasia type 3, (2) susceptibility to an intervertebral disc disease, and (3) hearing loss. Here, we describe the first autosomal recessive Stickler family due to loss of function mutations (c.1176_1198del, p.Gln393Cysfs*25) of COL9A3 gene. These findings extend further the role of collagen genes family in the disease pathogenesis.

Patients with distal deletions of chromosome 1q have a recognizable syndrome that includes microcephaly, hypoplasia or agenesis of the corpus callosum, and psychomotor retardation. Although these symptoms have been attributed to deletions of 1q42-1q44, the minimal chromosomal region involved has not yet defined. In this report, we describe a 7 years old male with mental retardation, cryptorchid testes, short stature and alopecia carrying only an interstitial de novo deletion of 911 Kb in the 1q43 region (239,597,095-240,508,817) encompassing three genes CHRM3, RPS7P5 and FMN2.