Clinical Characteristics of Children with Combined Pituitary Hormone Deficiency and the Effects of Growth Hormone Treatment.

AIM: We aimed to describe the clinical characteristics of patients with congenital combined pituitary hormone deficiency (CPHD) and evaluate the first-year growth responses of individuals with CPHD and isolated growth hormone deficiency (IGHD) in order to establish the influence of other hormone deficiencies on growth response. PATIENTS AND METHODS: This retrospective study was conducted in four tertiary care centers in Turkey. The records of patients diagnosed with CPHD (n=39) and severe IGHD (n=50) were collected. Cases with acquired lesions or chronic diseases were not included in the study. Data are presented as median (interquartile range). RESULTS: Among 39 patients (13 females; 33%) with a diagnosis of CPHD, the majority of patients (64%) presented initially with combined deficits at baseline examination, whereas isolated deficiencies (36%) were less prevalent. Among all patients with GH deficiency, TSH, ACTH, FSH/LH, and ADH deficiencies were present in 94%, 74%, 44%, and 9% of patients, respectively. Patients with CPHD were diagnosed at a younger age (4.9 (8.4) vs. 11.6 (4.1), p<0.001, respectively) and had lower peak GH concentrations (0.4 (1.8) vs. 3.7 (2.9), p<0.001, respectively) than patients with IGHD. Patients with IGHD and CPHD had similar first-year growth responses (Δheight SD score of 0.55 (0.63) vs. 0.76 (0.71), respectively, p=0.45). CONCLUSIONS: We established the nature and timing of numerous hormonal deficits emerging over time. We also identified that the existence of CPHD did not hinder growth response.

Impaired systolic and diastolic left ventricular function in children and adolescents with congenital adrenal hyperplasia receiving corticosteroid therapy.

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia. METHODS: The study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (>10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging. RESULTS: Patients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p<0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p<0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p<0.05). CONCLUSION: This study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

Prevalence of Endocrinopathies in Turkish Children With ß-Thalassemia Major: A Single-Center Study.

Present chelation protocols have increased the life quality and survival of the patients with ß-thalassemia major (BTM). However, endocrine complications are still mostly experienced. The aim of this study was to determine the prevalence of endocrine complications in children with BTM, and to study the relationship between serum ferritin levels and complications. Forty-five children (female: 23/male: 22, mean age: 12.39±3.72 y) with BTM were enrolled into the study. Blood samples were taken after an overnight fasting, early in the morning from entire study group. Median (range) serum ferritin of the patients was 1365 ng/mL (362 to 5996 ng/mL). The most prevalent endocrine complications were vitamin D insufficiency (54.5%), short stature (42%), pubertal impairment (25% for each sex), and osteopenia (13%), respectively. Ferritin levels were not correlated with anthropometric or laboratory data. Monitoring of growth, vitamin D status, and endocrine functions are essential to achieve a good quality of life in BTM patients.

Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation.

3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score -5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score -5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8-10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.

A novel mutation in a mother and a son with Aarskog-Scott syndrome.

Aarskog-Scott syndrome, also termed as faciogenital dysplasia, is an X-linked disorder consisting of short stature, craniofacial dysmorphism, shawl scrotum, cryptorchidism, and interdigital webbing. Cardiac and central nervous system abnormalities and behavioral disorders can also be detected. The gene responsible for the syndrome is called FGD1, located at Xp11.21. A 7-year-old boy was admitted to our hospital due to short stature. He was born to non-consanguineous parents after an uneventful term pregnancy. Orchiopexy for bilateral cryptorchidism was performed when he was 2 years old. At physical examination, his height was under 3 percentile, and he had broad nasal bridge, hypertelorism, wide philtrum, brachydactyly, and interdigital webbing. Cranial magnetic resonance imaging and echocardiography revealed normal findings. An eye examination showed amblyopia and astigmatism. The mother had short stature and interdigital webbing as well. Mutational analyses revealed a novel mutation (c.308-2G), hemizygous in the boy and heterozygous in the mother. Aarskog syndrome (faciogenital dysplasia) should be kept in mind in children with short stature and interdigital webbing.

Hyperprolactinemia in children: clinical features and long-term results.

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 ± 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). METHODS: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). CONCLUSIONS: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Evaluation of neutrophil gelatinase-associated lipocalin in normoalbuminuric normotensive type 1 diabetic adolescents.

AIMS: The aims of this study were to determine neutrophil gelatinase-associated lipocalin (NGAL) levels in normoalbuminuric and normotensive adolescents with type 1 diabetes and to assess the relationship between NGAL and clinical and laboratory variables. METHODS: Forty-six adolescents with type 1 diabetes [male/ female (M/F) ratio, 24/22; median age, 14.5 years; range, 12.2-16 years; diabetes duration, 4.8 years; range, 2.6-6.7 years; hemoglobin A1c (HbA1c), 7.9%; range, 7.2%-9.2%] and 21 healthy controls (M/F, 7/14; median age, 14.8 years; range, 13.6-15.5 years) were compared regarding clinical, laboratory, and ambulatory blood pressure monitoring variables. RESULTS: Median blood and urine glucose, HbA1c, urine NGAL/creatinine ratio [13.2 (range, 8.3-43.1) vs. 4.8 (range, 2.9-20.2), p = 0.015], and daytime systolic and diastolic blood pressure (BP) standard deviation score and BP loads were found higher in diabetic adolescents. Urine NGAL levels were found to be correlated with albumin/creatinine ratio (r = 0.452, p = 0.002), whereas plasma NGAL levels were correlated with nighttime systolic BP load (r = 0.309, p = 0.037). Patients with high-normal albuminuria (n=6) had higher urine NGAL levels [48.7 ng/mL (range, 27.9-149.1 ng/mL) vs. 14.3 ng/mL (range, 3.5-41 ng/mL), p = 0.014] and urine NGAL/creatinine ratio [39.3 ng/mg (range, 21.1-126.3 ng/mg) vs. 11.8 ng/mg (range, 6.3-40.9 ng/mg), p = 0.03] compared with those of controls and higher urine NGAL levels compared with that of diabetic adolescents with low-normal albuminuria [n=40, 11.2 ng/mL (range, 6-23.4 ng/mL), p = 0.004]. CONCLUSIONS: Normoalbuminuric and normotensive adolescents with type 1 diabetes have elevated urinary NGAL values, which might indicate kidney injury.

The relationship between urinary tract infection and calcium excretion in children.

The aim of this study was to investigate the relationship between urinary tract infection (UTI) and urinary calcium excretion. A total of 82 children (mean age: 5.41± 4.09 years) with UTI and 82 age- and sex-matched children as a control group were enrolled in the study. Urinary calcium excretion was studied in children with UTI before treatment, three days after treatment and six months after remission of UTI. Urine calcium/ creatinine ratio (UCa/cr) and 24-hour urinary calcium excretions were studied. UCa/cr ratios were also evaluated as percentile rates, which was performed in our previous study. The effects of the location of infection, complaints, family history of urolithiasis, and radiological findings on urinary calcium excretion were also investigated. UCa/cr ratio before treatment was found higher than in the control group (p=0.04). No statistically significant relationship was found between the pretreatment UCa/cr and sex, location of infection, family history, or radiological findings.

Bilateral pheochromocytoma as first manifestation of von Hippel-Lindau disease: a case report.

Von Hippel-Lindau syndrome is an autosomal dominant disorder that includes susceptibility to hemangioblastomas of the eyes and central nervous system, renal clear cell carcinoma, multiple pancreatic cysts, serous cystadenomas and pancreatic neuroendocrine tumors, pheochromocytoma, endolymphatic sac tumors, and cystadenomas of the epididymis and broad ligament. We present a 16-year-old male who had been followed for having bilateral adrenal, and in addition, extraadrenal multifocal pheochromocytoma for six years. At the age of 16, he presented with bilateral retinal hemangioblastomas, which led to the diagnosis of von Hippel-Lindau disease type 2A confirmed by genetic analysis. The patient's mother also had bilateral adrenal pheochromocytoma with no other von Hippel Lindau-associated tumor. In children, pheochromocytoma may be the only and/or initial manifestation of the disease with delayed manifestations of the syndrome in other organs. Von Hippel-Lindau disease is a complex multidisciplinary disorder that requires well-coordinated medical care. Surveillance of these patients and asymptomatic relatives may prevent morbidity and mortality and improve long- term prognosis. Molecular analysis of the von Hippel-Lindau gene is useful for early diagnosis of the disease in individuals who do not yet fulfill the clinical diagnostic criteria and is instrumental in the management and follow-up of the affected family.

Severe hypercalcaemia and acute renal failure in an infant with subcutaneous fat necrosis.

Subcutaneous fat necrosis (SFN) in the newborn is a form of panniculitis which presents with erythematous nodules and indurated plaques. Severe life-threatening hypercalcaemia can occur as a late complication. A 2-month-old girl presented with severe hypercalcaemia and acute renal injury as a complication of SFN. She was admitted to hospital with the chief complaint of failure to thrive. She had a history of therapeutic hypothermia. After successful treatment of the hypercalcaemia with bisphosphonates, the acute renal injury recovered spontaneously. In neonates with SFN, acute renal injury is a rare complication of hypercalcaemia. Timely prevention of the complications of hypercalcaemia in SFN is essential.

A mother and son with Noonan syndrome resulting from a PTPN11 mutation: first report of molecularly proven cases from Turkey.

Noonan syndrome is an autosomal dominant disorder characterized by short stature, typical craniofacial features, and congenital heart defects. The underlying genetic defects were not clear until 2001. This report is the first to describe a molecular analysis and associated clinical features of a Turkish mother and son, who were clinically diagnosed as Noonan syndrome when the boy was referred to our department due to short stature. The analysis revealed an A --> G transition at position 923 in exon 8 of the PTPN11 gene, indicating an Asn308Ser substitution.

Serum Nesfatin-1 Levels in Girls with Idiopathic Central Precocious Puberty.

OBJECTIVE: Nesfatin-1, an anorexigenic neuropeptide, is expressed mainly in the central nervous system and in some peripheral tissues. The role of nesfatin-1 in energy balance has been investigated. Despite the suggestion of a role for nesfatin-1 in reproductive function, data are limited on the role of nesfatin-1 in human puberty. METHODS: The aim of this study was to investigate the following: i) the role of nesfatin-1 in puberty, and ii) relationship between nesfatin-1 and anthropometric measurements and gonadotropin levels in girls with idiopathic central precocious puberty (CPP). Twenty-four girls with CPP (7.68±1.02 years) and 20 female, prepubertal, healthy controls (7.48±0.88 years) were enrolled in the study. All patients with CPP were treated by the intramuscular administration of leuprolide acetate at a daily dose of 3.75 mg for 28 days. Nesfatin-1 was measured before and during treatment. RESULTS: There was no difference in serum nesfatin-1 levels in girls with CPP and healthy controls [5.67 (2.5-20.6) mmol/L and 5.75 (2.51-9.64) mmol/L], respectively. There was a negative correlation between nesfatin-1 levels and body weight and body mass index-standard deviation score (p=0.01, r=-0.83; p=0.025, r=-0.81, respectively). No correlation was found between nesfatin-1 and gonadotropin, estradiol levels, uterine length or endometrial thickness. CONCLUSION: The results of this study suggest that there are no differences between girls with CPP and healthy, prepubertal girls regarding nesfatin-1 levels.

Urinary calcium excretion in healthy Turkish children.

The aim of this study was to establish the age related reference percentile values for urinary calcium excretion in healthy Turkish children, and to determine the frequency of hypercalciuria and also the factors affecting urinary calcium excretion. A cross-sectional study was performed in Aydin, in western Turkey during winter. Study population was constituted from seventeen districts of this region (sample size was calculated from a formula using the results of the last population census) by stratified and random sampling methods. Urinary calcium excretion was measured as the calcium/creatinine concentration ratio in the second non-fasting urine samples. A total of 2252 children (1132 male) with a mean age of 8.57 +/- 4.44 years (ranged from 15 days to 15 years) were studied. The mean of urinary calcium/creatinine concentration ratio was calculated as 0.092 +/- 0.123. The percentile values between 3rd and 97th for urinary calcium/creatinine concentration ratio according to age were calculated and shown as multiple line graphs. Hypercalciuria prevalence was found as 9.6% when the upper limit of urinary calcium/creatinine concentration ratio was accepted as 0.21. Urinary calcium/creatinine concentration ratio of the children from different districts, altitudes, and ethnic origins were statistically different. Poor negative correlations were found between urinary calcium/creatinine concentration ratio and age and weight. No differences in urinary calcium/creatinine concentration ratios were observed in terms of sexes, diet, physical activity, urolithiasis in the family, symptoms related to hypercalciuria, amount of calcium in drinking water, and urine strip analysis. In conclusion, reference values for urinary calcium/creatinine concentration ratios should be established for children in each country and also in each geographic region.

Persistent Müllerian duct syndrome: A novel mutation in the Αnti-Müllerian Ηormone gene.

BACKGROUND AND OBJECTIVE: Persistent Müllerian duct syndrome (PMDS) is a relatively rare form of 46,XY disorder of sex development caused by the failure of formation, release or action of anti-Müllerian hormone (AMH) in intrauterine life. In this report we describe a case diagnosed with PMDS with a novel homozygous mutation in the AMH gene. CASE REPORT: A 4-month-old male presented with bilateral cryptorchidism and normal external genitalia. The laboratory examination revealed normal gonadotropin levels for his age (FSH: 0.91 mIU/mL, LH: 1.23 mIU/mL, testosteron <0.13 ng/mL, respectively). AMH was undetectable (<0.01 ng/mL). Ultrasonography (USG) revealed absence of the left gonad and an intraabdominally located right gonad. Laparoscopy demonstrated the presence of a rudimentary uterus and fallopian tubes. Karyotyping revealed a normal 46,XY karyotype. Molecular genetic analysis demonstrated a novel homozygous mutation [p.C526F (c.1577G>T)] in the AMH gene. CONCLUSION: PMDS should be kept in mind in all cases with bilateral crytorchidism. Orchidopexy and resection of Mulletian duct derivates, exercising extra caution with regard to maintaining vascular supply to the testis, is the recommended approach.

A Novel Homozygous Mutation in the Transient Receptor Potential Melastatin 6 Gene: A Case Report.

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease caused by mutations in the transient receptor potential melastatin 6 (TRPM6) gene. Affected individuals present in early infancy with seizures caused by the severe hypocalcemia and hypomagnesemia. By presenting this case report, we also aimed to highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia. A Turkish inbred girl, now aged six years, had presented to another hospital at age two months with seizures diagnosed to be due to hypomagnesemia. She was on magnesium replacement therapy when she was admitted to our clinic with complaints of chronic diarrhea at age 3.6 years. During her follow-up in our clinic, she showed an age-appropriate physical and neurological development. In molecular genetic analysis, a novel homozygous frame-shift mutation (c.3447delT>p.F1149fs) was identified in the TRPM6 gene. This mutation leads to a truncation of the TRPM6 protein, thereby complete loss of function. We present the clinical follow-up findings of a pediatric HSH case due to a novel mutation in the TRPM6 gene and highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia.

Relationship between oxidative stress and blood glucose fluctuations evaluated with daily glucose monitoring in children with type 1 diabetes mellitus.

BACKGROUND: The aim of this study is to determine the relationship between oxidative stress marker (8-iso-prostaglandine F2α) and glycemic indices computed from daily glucose monitoring data in children with type 1 diabetes mellitus (T1DM). METHODS: Thirty-one children and adolescents with T1DM (median age 12.2 years) and healthy subjects (median age 11.7 years) were enrolled into the study. Anthropometric data were recorded for the entire group before the study. In addition, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c were recorded in T1DM subjects. T1DM subjects performed self-monitoring of blood glucose (SMBG) for a month (at least four times a day) for calculating glycemic indices. Twenty-four-hour urine 8-iso-prostoglandine F2α levels were studied at the end of the study period in the both groups. RESULTS: Median diabetes duration was 5 years, hemoglobin A1c (HbA1c) was 7.3%. Standard deviation (SD) of the blood glucose (BG) was determined as 85 mg/dL. Median urinary 8-iso-prostoglandine F2α was found to be significantly higher than that of the healthy subjects (2808.9 and 298 pg/mg creatinine, p<0.001, respectively). There was no correlation between urinary 8-iso-prostoglandine F2α and age, anthropometric data, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c, or SD of BG in T1DM groups. CONCLUSIONS: This study showed that, 8-iso-prostoglandine F2α that is an oxidative stress marker, is significantly higher in T1DM than that of healthy subjects while, no significant relation between glycemic indices and urinary 8-iso-prostoglandine F2α levels were demonstrated. Further studies are needed to assess other factors, and the relationship between glucose fluctuations and oxidative stress markers.

Evaluation of the relationship between serum adropin levels and blood pressure in obese children.

BACKGROUND: The prevalence of obesity and related cardiovascular comorbodities is increasing rapidly. Adipokines play a major role in the pathogenesis of obesity-related inflammation and hypertension. AIM: The aim of this study was to evaluate the serum adropin levels in obese children and to determine the relationship between adropin levels and blood pressure (BP) in the pediatric age group. METHODS: Forty obese children (mean age: 12.5 ± 2.5 years; male/female ratio: 18/22) and 15 healthy controls (mean age: 15 ± 3.14 years; male/female ratio: 5/15) were included in the study. Serum adropin levels, and a number of laboratory and clinical variables were compared. Ambulatory blood pressure monitoring was performed on obese subjects. Relationship between adropin levels and BP variables was examined. RESULTS: Serum adropin levels were significantly lower in obese subjects than in healthy controls (193.56 ± 94 vs. 289 ± 187 pg/mL, p = 0.03). Adropin levels were correlated negatively with body mass index z-score (r = -0.56; p = 0.034). There was no correlation between serum adropin levels and laboratory variables in obese subjects. Five of the patients (12.5%) were nondipper, and nine of the patients (22.5%) had hypertension. There was no significant correlation between serum adropin levels and BP variables. CONCLUSION: Serum adropin levels were significantly lower in obese children; however, there was no correlation between serum adropin levels and BP variables. Further studies are needed to determine the role of adipokines on BP.

The Role of Thyrotropin-Releasing Hormone Stimulation Test in Management of Hyperthyrotropinemia in Infants.

OBJECTIVE: Hyperthyrotropinemia, which can be either a permanent or a transient state, is an asymptomatic condition and there is a controversy in management and long-term consequences. The aim of this study was to evaluate the results of thyrotropin-releasing hormone (TRH) test in infants with hyperthyrotropinemia. METHODS: Data of the patients who underwent a TRH test for mildly elevated thyroid-stimulating hormone (TSH) levels between 2004 and 2011 in a single academic pediatric endocrinology unit were retrospectively reviewed from the case files. RESULTS: Twenty infants (13 female, 7 male) with the median (range) age of 33 days (25-50) were enrolled into the study. The median basal TSH was 7.0 mIU/L (4.9-8.9) and free thyroxine level was 1.4 ng/mL (1.2-1.6) at the time of the TRH test. Thyroid ultrasonography was performed to 10 of the cases, and one of them had thyroid hypoplasia. TRH test revealed normal results in four infants, while sixteen infants had exaggerated response suggestive of primary hypothyroidism. The median follow-up period was 3.5 years (2.3-3.7). Therapy was discontinued in seven cases (2 had normal TRH response, 5 had exaggerated response) with the median age of 3.2 years (2.5-4). Of these seven infants, three had an elevated TSH on follow-up and L-thyroxine was restarted. All of the infants, in whom therapy was restarted, had exaggerated response to TRH. CONCLUSION: TRH test response could be a useful diagnostic test to evaluate the persistence of the disease during the infantile age period.

Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing.

AIM: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship. METHODS: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses. RESULTS: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations - three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic. CONCLUSION: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.