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Background. The frequency of subclinical hypothyroidism (SH) in patients with obesity is increased compared with the normal population. However, data on the risk of cardiovascular disease (CVD) in patients with SH are still scarce. Lipid parameters are strong predictors of early CVD. We aimed to investigate the role of lipid indices in predicting CVD risk compared to conventional lipid components. Methods. A total of 220 euthyroid obese children (EU) and 90 obese children with SH were included in the study. All data were collected from hospital files. Lipid indices were evaluated. Atherogenic index of plasma (AIP), cardiac risk ratio (CRR) and atherogenic coefficient (AC) were calculated. AIP>0.24, CRR>5 ve AC>3 were considered as cardiovascular risk criteria. Results. The presence of SH increased the risk of higher AIP and the risk of CRR, compared to euthyroid obese children. Conclusion. Subclinical hypothyroidism in obese children may cause dislipidemia carrying a high cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Context. The links between obesity and thyroid function or thyroid volume in children are still controversial with limited available data. Objective. This study aimed to examine thyroid function and volume in obese Turkish school-age children in comparison to normal-weight children. Design. Cross-sectional study. Subjects and Methods. One hundred obese children (47 boys, 53 girls; mean age 10.34±2.79 years) with a body mass index (BMI) above 95th percentile, and 100 normal-weight children (42 boys, 58 girls; 10.34±2.79 years) were included. The study parameters were BMI z score (Z-BMI), body surface area (BSA), thyroid volume, free thyroxine (fT4) and thyroid stimulating hormone (TSH) levels. Results. The mean TSH and fT4 levels did not show a significant difference between obese and normal-weight children (p>0.05). The mean thyroid volume was higher in obese children (6.46±5.84 and 4.64±1.44, respectively; p=0.043). fT4 correlated negatively with Z-BMI in both normal-weight and obese children (r=-0.285, p=0.004 and r=-0.289, p=0.004, respectively). Thyroid volume, on the other hand, correlated positively with Z-BMI, again in both normal-weight and obese children (r=0.657, p<0.001 and r=0.444, p<0.001, respectively). Similar associations were found for BSA. Conclusions. Thyroid volume correlated positively and fT4 correlated negatively with Z-BMI and BSA, in both obese and normal-weight school-age children, whereas TSH appears to be independent of these parameters. [ABSTRACT FROM AUTHOR]

Transaldolase deficiency is a rare inborn autosomal recessive disorder caused by biallelic mutations in the TALDO1 gene. It is characterized by intrauterine growth restriction, dysmorphism, abnormal skin, cytopenia, hepatosplenomegaly, liver cirrhosis, endocrine problems, renal and cardiac abnormalities. We present two siblings of Turkish origin with early-onset form of transaldolase deficiency and hypergonadotropic hypogonadism in both sexes. The girl (index) was followed-up with cryptogenic cirrhosis, leukopenia and thrombocytopenia, skin abnormalities, congenital heart defects, hypercalciuria, nephrolithiasis, proteinuria, chronic kidney disease throughout childhood. She developed hypergonadotropic hypogonadism in adolescence period. Whole exome sequencing due to the multisystemic involvement revealed a previously described homozygous inframe deletion in TALDO1 gene. Her brother was born as a small for gestational age baby and was also followed-up with cryptogenic cirrhosis since his infancy, together with cytopenia, congenital heart defects, bilateral cryptorchidism, short stature, hypercalciuria, proteinuria and chronic kidney disease in childhood. He presented with testicular microlithiasis and hypergonadotropic hypogonadism in adolescence. Sanger sequencing of TALDO1 gene confirmed the presence of the same homozygous deletion with his sister. The mother was found to be a heterozygous carrier for this deletion. We describe two patients with multisystemic involvement since neonatal period who presented with an additional hypergonadotropic hypogonadism in adolescence. The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions especially during puberty.

Background: Biallelic loss-of-function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV-related smooth muscle tumors. Clinical and immunological characterizations of the disease with long-term follow-up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long-term efficacy of treatment in controlling different disease manifestations., Methods: The presenting phenotypes, long-term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2-deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cT FH ) cells were analyzed. Three-dimensional (3D) migration assay was performed to determine T-cell shape., Results: Mean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV-related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4 + T cells, Treg, and cT FH cells. Memory B and NK cells were also decreased. CARMIL2-deficient T cells exhibited reduced T-cell proliferation and cytokine production following CD28 co-stimulation and normal morphology when migrating in a high-density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow-up of 10.8 years (range: 3-17 years)., Conclusion: This cohort provides clinical and immunological features and long-term follow-up of different manifestations of CARMIL2 deficiency., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background & Aims: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date., Methods: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category., Results: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 μmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001)., Conclusions: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS., Lay Summary: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease., Competing Interests: Conflicts of interest Daan B.E. van Wessel: [nothing to disclose], Richard J. Thompson [consultancy for Shire, Albireo, Mirum, Horizon Pharmaceuticals, Sana Biotechnology, GenerationBio, Retrophin and Qing Bile Therapeutics], Emmanuel M. Gonzales [Consultant for CTRS and Mirum Pharmaceuticals], Irena Jankowska [nothing to disclose], Tassos Grammatikopoulos [nothing to disclose], Agustina Kadaristiana [nothing to disclose], Patryk Lipiński [nothing to disclose], Piotr Czubkowski [nothing to disclose], Nathalie Rock [nothing to disclose] Emmanuel Jacquemin [nothing to disclose], Anne Spraul [nothing to disclose], Etienne M. Sokal [founder and CSMO of Promethera Biosciences], Mohammad Shagrani [nothing to disclose], Dieter Broering [nothing to disclose], Talal Algoufi [nothing to disclose], Nejat Mazhar [nothing to disclose], Emanuele Nicastro [nothing to disclose] Deirdre Kelly [Consultant for Albireo], Gabriela Nebbia [nothing to disclose], Henrik Arnell [consultant for Albireo and Mirum Pharmaceuticals], Björn Fischler [has attended one advisory board meeting with Albireo in 2016], Jan Hulscher [nothing to disclose], Daniele Serranti [nothing to disclose], Cigdem Arikan [nothing to disclose], Esra Polat [nothing to disclose], Dominique Debray [consultant for Alexion pharmaceuticals], Florence Lacaille [nothing to disclose], Cristina Goncalves [nothing to disclose], Loreto Hierro [nothing to disclose], Gema Muñoz Bartolo [nothing to disclose], Yael Mozer-Glassberg [nothing to disclose], Amer Azaz [nothing to disclose], Jernej Brecelj [nothing to disclose], Antal Dezsőfi [nothing to disclose], Pier Luigi Calvo [nothing to disclose], Enke Grabhorn [nothing to disclose], Ekkehard Sturm [nothing to disclose] Wendy van der Woerd [nothing to disclose], Binita Kamath [consultant for Mirum Pharmaceuticals, Shire and DCI], Jian-She Wang [nothing to disclose], Liting Li [nothing to disclose], Özlem Durmaz [nothing to disclose], Zerrin Onal [nothing to disclose], Ton Bunt [nothing to disclose], Bettina Hansen [consultant for Mirum Pharmaceuticals, Albireo AB, Chemomab, Calliditas, Intercept, Cyma Bay, unrestricted grants from Cyma bay, Intercept, Mirum and Albireo], Henkjan J. Verkade [Consultant for Danone/Nutricia Research, Ausnutria BV, Albireo AB, GMP+Orphan, Mirum Pharmaceuticals, Intercept and Vivet]. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. All rights reserved.)

Background: In this study we evaluated whether vitamin B12 deficiency affects neonatal screening (NS) for congenital hypothyroidism (CH)., Methods: A cross-sectional study conducted from 2010 to 2011. A total of 10,740 infants were born in our hospital in this period. Thyroid-stimulating hormone (TSH) was tested for NS and neonates with abnormal screening results (TSH>20 mIU/L) were re-examined. Two hundred and twenty-nine re-called subjects (re-call rate 2.3%) were compared to 77 randomly selected newborns with normal TSH screening among these term newborns in terms of serum TSH, free T4, vitamin B12 and homocysteine status., Results: Of the 229 re-called subjects, 11 infants with CH and 21 infants with transient TSH elevation were detected. In the normal TSH screening group, only two infants were diagnosed with transient TSH elevation. Mean serum B12 levels were 126.4±48.7 pg/mL and 211.9±127.9 pg/mL in the positive TSH-screening group and the control group, respectively. There was a significant difference between positive and normal TSH-screening groups in regard to serum TSH, free T4, serum B12 and homocysteine levels., Conclusions: We found a significant vitamin B12 deficiency in positive TSH-screening infants. Beside the crucial role of vitamin B12 in newborns, deficiency seems to increase the recall rates of infants in an NS program for CH.

Background: Type 1 diabetes mellitus (T1DM) is speculated to have an impaired immunological response to vaccines. This paper aimed to investigate the presence of specific antibodies against hepatitis B virus (HBV) and measles in diabetic children who had been immunized according to the standard national calendar of immunization., Methods: Two hundred and one diabetic children and 140 healthy controls were prospectively evaluated. Antibodies against hepatitis B (anti-HBs) and measles were detected in all individuals who completed the vaccination schedule. We noted onset of T1DM, duration of the disease, diabetes-related autoantibodies and mean HbA1c levels., Results: Some 72.6% of diabetics and 82.1% of controls had anti-HBs (+) (p=0.04). We found a reduced efficacy of measles vaccination in anti-HBs (-) diabetic children (p=0.009), even though there was no significant difference between the study and control groups. Onset of the disease was earlier in anti-HBs (-) diabetics than in controls (p=0.038). No difference with respect to other parameters was found., Conclusions: Our data showed a reduced seroprotection rate for HBV vaccination in diabetic children and for measles with anti-HBs (-) diabetics. Larger studies should be encouraged to confirm the vaccine efficacy in diabetic children and to elucidate possible pathogenic mechanisms.

Colorectal carcinoma (CRC) is an extremely rare tumor of childhood that can be associated with cancer predisposition syndromes. A patient with CRC related to constitutional mismatch repair deficiency (CMMRD) syndrome with features of neurofibromatosis type 1 (NF-1) is presented here. A 13-year-old boy was admitted for a 4-month history of diarrhea and rectal bleeding. The patient had extensive café au lait spots, freckling, and Lisch nodules. He fulfilled the NF-1 diagnostic criteria. Colonoscopy showed numerous polyps and a colorectal mass lesion, of which a biopsy revealed adenocarcinoma, an uncommon pathology associated with NF-1. High microsatellite instability and homozygous mutation of PMS2 gene in tumor tissue and blood lymphocytes, respectively, confirmed the diagnosis of CMMRD. Unfortunately, because family history related to CMMRD was negative, the parents denied the diagnosis and refused the therapy, and the patient was lost to follow-up. CMMRD is a rare cancer predisposition syndrome with phenotypical features resembling NF-1. The disease may be suspected in the setting of NF-1 features and CRC, high-grade brain tumors, or hematologic malignancies. Lack of family history related to CMMRD may be a major obstacle to convincing parents of the presence of an inherited disease in their progeny., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: Caustic substance ingestion in childhood is a public health issue in developing countries, and several management protocols have been proposed to prevent the resulting esophageal strictures. The role of corticosteroids in preventing corrosive-induced strictures is controversial. Our aim was to study the influence of high doses of corticosteroids in preventing esophageal strictures., Methods: Eighty-three children with a mean age of 4.10 6 2.63 years and with grade IIb esophageal burns (an esophagogastroscopy was performed within 24–48 hours of injury) due to corrosive substance ingestion were enrolled in our study between 2005 and 2008. Forty-two children (study group) received methylprednisolone (1 g/1.73 m2 per day for 3 days), ranitidine, ceftriaxone, and total parenteral nutrition. Forty-one children (control group) were administered the same regimen excluding methylprednisolone. Stricture development was compared between groups based on endoscopic and radiologic findings., Results: During the endoscopic examination, stricture development was observed in 4 patients (10.8%) in the study group and in 12 patients (30%) in the control group. The difference was statistically significant (P = .038). The stricture development rate in the upper gastrointestinal system with barium meal was 14.3% and 45.0% in the study and control groups, respectively. The difference was statistically significant (P = .004). The duration of total parenteral nutrition was shorter in the study group compared with the control group (P = .001). High doses of methylprednisolone were well tolerated in the study group without any side effects., Conclusions: High doses of methylprednisolone used for the management of grade IIb esophageal burns may reduce stricture development.

Aim: Assisted reproduction technology is used widely all over the world. There is a great concern about the morbidity of in vitro fertilization (IVF) babies, but investigations are mostly related to mechanical conditions that are attributed to multiparity. This paper aimed to investigate the effect of IVF on thyroid functions in newborns., Methods: A total of 98 healthy, term IVF newborns were evaluated between postnatal 2-4 weeks of age by screening of thyroid functions between July 2006 and April 2008. Ten subjects were assessed as a study group whose thyroid-stimulating hormone (TSH) levels were higher than 6.5 mU/L. Control group consisted of randomly selected 10 naturally conceived infants with hyperthyrotropinemia (whose TSH levels were higher than 6.5 mU/L but under 15 mU/L) with the same age. All children were thoroughly examined, and serum fT4, TSH, anti-thyroid peroxidase and anti-thyroglobulin antibodies were measured, and a thyrotropin-releasing hormone (TRH) test was performed in all subjects in both groups., Results: Euthyroid hyperthyrotropinemia was diagnosed in approximately 10% of IVF babies. Exaggerated TSH levels to TRH were obtained in all IVF babies (subclinical hypothyroidism) but in none of the controls. A significant difference was noted in the concentration of TSH at the 20th min between the two groups (p < 0.001). Besides, sustained and delayed TSH responses were observed in IVF babies. Neonatal screening tests were negative in both of the groups., Conclusion: In IVF babies, despite normal neonatal screening tests, subclinical hypothyroidism might be observed that suggests the need for screening in this respect., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Pseudohypoaldosteronism type 1 (PHA1) is a disease involving a state of renal tubular unresponsiveness to the action of aldosterone and characterized by excessive salt loss in the urine, hyperkalemia, and metabolic acidosis. In kidney, PHA1 may occur primarily by mutations in the subunits of the sodium channel or in the mineralocorticoid receptors, and secondarily by several renal disorders. Miliaria rubra and thrombocytosis are reported in a 6-month-old girl with PHA1. In patients with PHA1, miliaria rubra-like cutaneous eruptions are suggested to occur due to obstruction of eccrine sweat glands through inflammation caused by excessive sodium excretion in sweat during hyponatremic crises. The presence of thrombocytosis in patients with PHA1 has not been previously reported. A hypothesis is proposed suggesting that sympathetic activation which provides vascular tonus during sodium excretion in sweat and salt-depletion crisis may play a role in the development of eruptions and thrombocytosis in patients with PHA1.

Arachnoid cysts are mainly manifested with the consequent neurological disorders. Even though these cysts may interfere in many systems due to their localizations, there is little information concerning their involvement in endocrinological disorders. We emphasize endocrinological functions together with cyst localizations and neurological disorders in childhood. A total of 50 patients diagnosed with arachnoid cysts were screened for cyst localizations, neurological symptoms and endocrinological outcomes evaluated by pubertal and growth status and hypothalamopituitary insufficiency. We investigated the interactions of these parameters. Arachnoid cysts were localized mostly in the middle fossa (54%) and posterior fossa (26%). Middle fossa cysts had a strong predilection for male gender (66.7% male) and left hemispheric dominancy (77%). We detected growth hormone deficiency in six patients, obesity in six patients and central precocious puberty in one patient; cysts were in the temporal area in three of the obese cases. All patients in our study had normal levels of cortisol, thyroid hormones and prolactin. In pediatric patients with arachnoid cysts, endocrinological follow-up is crucial as neurological outcomes and further evaluations are needed, mainly to confirm pubertal and growth status.

In order to prevent and control non-communicable diseases (NCDs), the 61st World Health Assembly has endorsed an NCD action plan (WHA resolution 61.14). A package for essential NCDs including chronic respiratory diseases (CRDs) has also been developed. The Global Alliance against Chronic Respiratory Diseases (GARD) is a new but rapidly developing voluntary alliance that is assisting World Health Organization (WHO) in the task of addressing NCDs at country level. The GARD approach was initiated in 2006. GARD Turkey is the first comprehensive programme developed by a government with all stakeholders of the country. This paper provides a summary of indicators of the prevalence and severity of chronic respiratory diseases in Turkey and the formation of GARD Turkey.

The molecule of the title compound, C(22)H(19)N(3)O(2)S, is not planar. The dihedral angle between the two phenyl rings is 27.46 (7) degrees and in the dihydropyrazolopyrimidine ring the total puckering amplitude Q(T) is 0.526 (3) A. The structure is stabilized by both intra- and intermolecular C-H.O interaction, and by an intermolecular N-H.S hydrogen bond.