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Diabetic autonomic neuropathy (DAN) commonly complicates diabetes and is associated with increased mortality rates over 5 yr. This fact denotes the significance of DAN prevention, mainly with effective glycemic control. However, total prevention of autonomic neuropathy in diabetic patients is not achievable. Thus, the timely detection of DAN and the use of effective means to improve autonomic nervous system function or slow down its progression become of utmost significance. Heart rate variability (HRV) is a technique that measures the beat-to-beat variability in RR intervals, which reflects changes in autonomic activity and their impact on cardiovascular function. Circadian variation in time and frequency domains of heart variability has been shown to correlate with circadian rhythm of ambulatory ischemia and suggests that relative changes in vagal and sympathetic tone at different times during the day may have a direct relationship to the severity of clinical events. Forty-seven (21 boys and 26 girls) type I insulin-dependent diabetics and 46 control subjects (19 boys and 27 girls) were included in the study. Our investigation demonstrated that overall HRV is markedly depressed in diabetes mellitus (DM). All time domain parameters except standard deviation of all 5-min mean RR intervals and all frequency domain indices maintain significant circadian variation. These changes in overall HRV and HRV circadian rhythms reflect significant reductions in cardiac parasympathetic activity and, possibly, increased sympathetic tone. [ABSTRACT FROM AUTHOR]

Since 1977, various reports have been published concerned with locomotor system involvement in thalassaemia minor. In this blind study, a further 80 cases with thalassaemia minor were evaluated and compared with 63 healthy controls. In 52% of thalassaemia minor cases and 54% of controls, varying musculoskeletal involvement was found by means of history, clinical examination and radiological investigation. Three patients had a history of short-lived arthritis. It was concluded that arthraigia was the most frequent finding, and hands (wrist) and shoulders were mostly involved. [ABSTRACT FROM PUBLISHER]

Objective: A series of aromatic thiosemicarbazone-oxime [TP1 and TP2] derivatives and their Ni(II), Cu(II), and Co(II) complexes were synthesized, and their larvicidal activity was evaluated against Aedes aegypti and Aedes albopictus larvae. The efficacy of these substances to Aedes albopictus larvae has been demonstrated for the first time., Methods: Laboratory colonized Aedes aegypti and Aedes albopictus larvae were subjected to larvicidal activity tests. Larval mortality rates at 24 and 48 hours were recorded and LC 50 values were calculated. The study was carried out at Aydın Adnan Menderes University in 2021., Results: For Aedes aegypti , LC 50 of TP1 and its Co(II) complex were 15.41, 9.75, μg/mL whereas for TP2 and its Co(II) complex, LC 50 were 21.62, 20.50 μg/mL after 24 and 48 h respectively. For Aedes albopictus , TP1 and its Co(II) complex showed an LC 50 of 12.06, 8.75 μg/mL, whereas TP2 and its Co(II) complex showed an LC 50 of 32.87, 25.48 μg/mL, for 24, and 48 h respectively., Conclusion: Both TP1 and TP2 compounds and their Co(II) complexes presented high efficacy against the larvae; it can be said that C=S groups in thiosemicarbazone derivatives are effective in showing activity and for this reason, studies should be continued to make these components effective.

Objective: Iodine deficiency (ID) continues to be a problem around the world. This study investigated the prevalence of ID and goiter among school-age children in the city center of Antalya, Turkey. The aim was to investigate the effect of an iodization program, which had been running for sixteen years, on nutritional iodine status in this population., Methods: A total of 1,594 school children, aged 6-14 years, were included in this cross-sectional study. ID was evaluated based on median [interquartile range (IQR)] urine iodine/creatine (UI/Cr) (μg/g) ratio and median (IQR) UI concentrations (UIC) (μg/L). UICs were measured using the Sandell-Kolthoff method. Goiter was determined by palpation and staged according to World Health Organization classification., Results: Median (IQR) UIC was found to be 174.69 (119.17-242.83) μg/L, and UIC was found to be lower than 50 μg/L in 6.5% of the population. The median UI/Cr ratio increased from 62.3 to 163.3 μg/g and goiter rates had decreased from 34% to 0.3% over the 16 years of the program. However, 19% were still classified as ID (mild, moderate or severe) and, furthermore, 11.5% were classified as excessive iodine intake., Conclusion: Comparison of two cross-sectional studies, carried out 16-years apart, showed that Antalya is no longer an ID region. However, surveillance should be continued and the percentage of ID and iodine excess individuals in the population should be monitored to avoid emerging problems.

Objective: Childhood obesity (OB) is an acknowledged global problem with increasing prevalence reported around the world. We conducted this study with the aim of determining the local trend in OB and overweight (OW) prevalence in the last decade and to observe the alteration of OB and OW prevalence by age group. An additional aim was to construct new age- and gender-specific body mass index (BMI) reference percentile charts for Turkish children living in the city center of Antalya., Methods: This cross-sectional study included 1687 school aged children. International Obesity Task Force guidelines were used to determine the OB and OW prevalence. OW was defined as a BMI between 85 th and 95 th percentile, and OB >95 th percentile. The data were compared with a previous study carried out in the same region in 2003. The least mean square method was used to construct the BMI reference percentile charts., Results: The prevalence rates for OB and OW were 9.8% and 23.2%, respectively, with a combined OW/OB rate of 33%. OB prevalence was higher in boys than girls (p<0.05). The prevalence of combined OW/OB was highest at age 9-10 years. The prevalence of OB has increased 2.9 times during twelve years in this location., Conclusion: Comparing the current findings with rates of OW and OB in the previous decade, childhood OB in Antalya has reached alarming levels. Urgent measures integrated into the national education system should be taken to prevent OB. In addition more surveillance studies should be planned to show the future trend of OB prevalence nationally.

In girls, breast development before eight years of age is called "premature thelarche (PT)". There are few studies in literature that show the interaction between PT and phthalate exposure. The aim of this study was to determine the urinary levels of di-(2-ethylhexyl) phthalate (DEHP) metabolites and other phthalate metabolites in girls with PT. PT group consisted of 29 newly diagnosed subjects. Control group comprised of healthy age-matched girls (n = 25). Urinary phthalate metabolite concentrations were measured by liquid chromatography/tandem mass spectroscopy (LC-MS/MS). The urinary concentrations of mono-(2-ethyl-hexyl)phthalate (MEHP) in the PT group (33.96 ± 6.88 μg/g creatinine) were found to be significantly higher compared to control group (11.54 ± 1.39 μg/g creatinine, p = 0.002). In PT group, %MEHP was also markedly higher vs. control (17.84 ± 3.31 vs. 6.44 ± 1.13, p = 0.001). Our results suggest that DEHP is more efficiently converted to MEHP in girls with PT, the importance of which needs to be further elucidated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The aim of the study was to assess the response to growth hormone (GH) treatment in very young patients with GH deficiency (GHD) through a national, multi-center study. Possible factors affecting growth response were assessed (especially mini-puberty)., Methods: Medical reports of GHD patients in whom treatment was initiated between 0 and 3 years of age were retrospectively evaluated., Results: The cohort numbered 67. The diagnosis age was 12.4±8.6 months, peak GH stimulation test response (at diagnosis) as 1.0±1.4 ng/mL. The first and second years length gain was 15.0±4.3 and 10.4±3.4 cm. Weight gain had the largest effect on first year growth response; whereas weight gain and GH dose were both important factors affecting second year growth response. In the multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response was significantly greater than in the isolated GH deficiency (IGHD) group (n=17) (p=0.030). In addition first year growth response of infants starting GH between 0 and 12 months of age (n=24) was significantly greater than those who started treatment between 12 and 36 months of age (n=43) (p<0.001). These differences were not seen in the second year. Δ Length/height standard deviation score (SDS), Δ body weight SDS, length/height SDS, weight SDS in MPHD without hypogonadism for the first year of the GH treatment were found as significantly better than MPHD with hypogonadism., Conclusions: Early onsets of GH treatment, good weight gain in the first year of the treatment and good weight gain-GH dose in the second year of the treatment are the factors that have the greatest effect on length gain in early onset GHD. The presence of the sex steroid hormones during minipubertal period influence growth pattern positively under GH treatment (closer to the normal percentage according to age and gender).

Wolfram syndrome (WS) is an autosomal recessive disorder caused by mutations in WFS1 gene. The clinical features include diabetes insipidus, diabetes mellitus (DM), optic atrophy, deafness, and other variable clinical manifestations. In this paper, we present the clinical and genetic characteristics of 3 WS patients from 3 unrelated Turkish families. Clinical characteristics of the patients and the age of onset of symptoms were quite different in each pedigree. The first two cases developed all symptoms of the disease in their first decade of life. The heterozygous father of case 2 was symptomatic with bilateral deafness. The first ocular finding of one patient (patient 3) was bilateral cataract which was accompanying DM as a first feature of the syndrome. In this patient's family, there were two members with features suggestive of WS. Previously known homozygous mutations, c.460+1G>A in intron 4 and c.1885C>T in exon 8, were identified in these cases. A novel homozygous c.2534T>A mutation was also detected in the exon 8 of WFS1 gene. Because of the rarity and heterogeneity of WS, detection of specific and nonspecific clinical signs including ocular findings and family history in non-autoimmune, insulinopenic diabetes cases should lead to a tentative diagnosis of WS. Genetic testing is required to confirm the diagnosis.

Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism caused by a number of loss-of-function mutations in the ALPL gene. It is characterized by defective bone and tooth mineralisation associated with low serum and bone alkaline phosphatase activity. The clinical presentation of this disease is extremely variable. For this reason, the diagnosis can be difficult and is often missed out or delayed. Hypophosphatasia is classified into subtypes based on the age of onset and clinical features. The clinical severity is associated with the age at diagnosis and the lack of tissue-nonspecific alkaline phosphatase activity; the severe forms of hypophosphatasia are primarily perinatal and infantile forms. Severe forms may present with many neurological problems such as seizures, hypotonia, irritability. Herein, we report the case of an infantile hypophosphatasia patient who presented with pyridoxine-responsive seizures and a novel homozygous mutation in the ALPL gene was detected. There is a limited number of hypophosphatasia patients with pyridoxine-responsive seizures in the literature, so early diagnosis of infantile hypophosphatasia in the clinically compatible patients allows more effective postnatal care/management and genetic counseling for further pregnancies.

Mucolipidosis II or I-cell disease is a rare lysosomal enzyme hydrolase trafficking due to deficient activity of the multimeric enzyme UDP-Nacetylglucosamine-l-phosphotransferase. It is a severe inborn error of lysosomal storage that causes progressive multisystem deterioration and death within the first year of life. The diagnosis of ML II is often difficult in an infant due to clinical variety, phenotypic overlap and the enzyme analysis required. Mucolipidosis II and rickets may have similar physical, biochemical and radiographic findings in newborns. The diagnosis of Mucolipidosis II is often missed, as it may present with rickets-like picture. In this article, we describe two neonatal mucolipidosis II patients mimicking rickets, and we evaluated them by clinical, metabolic and imaging findings via literature and also emphasized the difficulties in diagnosis of this rare disease.

Objective: Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey., Methods: A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers., Results: Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height., Conclusion: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Aim: Recently, it was reported that the development of breast tissue and secondary sex characteristics in girls occurred at much younger age and the incidences of premature thelarce (PT) and central idiopathic precocious puberty (ICPP) are increasing. In this context, we wanted to evaluate the mycoestrogen exposure as triggering factor for premature sexual development., Methods: The girls living in Mediterranean region of Turkey were divided in to three groups: control (N.=25; mean age: 6.45 ± 1), PT (N.=28; mean age: 6.86 ± 0.95) and ICPP (N.=25; mean age: 6.97 ± 0.87). Urinary ZEN levels were measured by using ELISA technique and were normalized by urinary creatinine levels. Body Mass Index (BMI) was evaluated and sex hormone levels were also measured., Results: We found that urinary ZEN was detectable in ~81% of all samples and observed an increase of ~2-fold in PT and a significant increase ~2.8-fold in ICPP group vs. control. We did not find any significant correlations between urinary ZEN levels and BMI and sex hormones in any of the groups., Conclusion: To our knowledge, this is the first study evaluating urinary ZEN levels in PT and ICPP Turkish patients. We can postulate that ZEN exposure can contribute to the etiology of PT and PP; however further studies on large number of subjects are needed to confirm the present data.

The aim of this study was to evaluate the endocrinological complications of the patients with thalassemia major (TM) who underwent bone marrow transplantation (BMT) and followed-up more than two years in our center, prospectively. "BMT group" consisted of 41 patients with TM. The mean age was 12.4 ± 5.4 years and transplantation age was mean 7.5 ± 4.9 years. Post-BMT follow-up lasted from 24 to 122 months (mean 65.07 months). Also, 32 TM patients with similar age group and same history of transfusion and chelation therapy were recruited for the study as "control (C) group". The weight SDS score after transplantation was found better than before transplantation (p = 0.010). There was a negative correlation between height SDS and BMT age (p = 0.008). The height SDS scores were better in patients whose BMT age was under seven years old compared to those older than seven years old (p = 0.02). Z-scores of femur neck and L2-4 vertebrae DEXA were decreased (p = 0.032, p = 0.0001) and incidence of insulin resistance increased (p = 0.01) in patients with increased BMT age. The risk of gonadal insufficiency was significantly lower in the patients who underwent BMT <7 years of age (p = 0.009). There was no statistically significant relationship between BMT age and complications such as hypothyroidism, hypoparathyroidism, and adrenal insufficiency. The patients with TM should be evaluated for transplantation in early stage of the disease, especially before the age of seven years. Because the BMT cannot correct the endocrinological complications of TM completely, the patients should be followed up regularly after the transplantation.

Steroid 5-a reductase type 2 isoenzyme (SRD5A2) deficiency is a male-limited autosomal recessive disorder that results in decreased conversion of testosterone to dihydrotestosterone with various de.gree of incomplete virilization in affected 46, XY infants. No clear genotype-phenotype relationship has been reported till date; moreover, the same mutation can result in considerable heterogeneity in clinical manifestations. Of 6 documented cases with Try235Phe homozygous mutation of the SRD5A2 gene, 3 patients had predominantly female external genitalia whereas the other 3 had predominantly male phenotype. We report Try235Phe homozygous mutation of the SRD5A2 gene in a Turkish patient who was initially assigned as a girl because of the predominantly female appearance of the external genitalia.

Objective: Bisphenol A (BPA) is an industrial chemical, particularly used to harden plastics. BPA is thought to have negative health effects on both laboratory animals and humans. Consider ing the decline in age of onset of puberty noted in recent years, particularly among girls, the importance of BPA as an estrogenic endocrine disruptor has increased. In this study, we aimed to determine urinary BPA levels in girls with idiopathic central precocious puberty (ICPP)., Methods: Non-obese girls newly diagnosed with ICPP (n=28, age 4-8 years) constituted the study group. The control group consisted of 25 healthy age-matched girls with no history of ICPP or any other endocrine disorder. Urinary BPA levels were measured by using high-performance liquid chromatography., Results: In the ICPP group, urinary BPA levels were significantly higher compared to the control group [median 8.34 (0.84-67.35) μg/g creatinine and 1.62 (0.3-25.79) μg/g creatinine, respectively (OR=8.68, 95% CI:2.03-32.72, p=0.001)]. There was no marked correlation between urinary BPA levels and body mass index in either group. In the ICPP group, no significant correlations were found between urinary BPA levels and serum luteinizing hormone, follicle-stimulating hormone and estradiol levels., Conclusions: To our knowledge, this is the first study evaluating the urinary BPA levels in Turkish girls with ICPP. Our results indicate that the estrogenic effects of BPA may be an etiologic factor in ICPP.

Williams-Beuren syndrome (WBS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability with a typical neurobehavioral profile, cardiovascular anomalies, and occasional infantile hypercalcemia. Majority of cases occur sporadically, and only a few cases of familial WBS have been reported. Although pre- and post-natal growth retardation is a common clinical feature of the syndrome, growth hormone deficiency is detected only in a few patients. To our knowledge, there has only been one report about familial Williams-Beuren syndrome in the Turkish population. Here, we report on the three molecular cytogenetically confirmed familial Williams-Beuren syndromes detected in a family with familial short stature. The father, daughter, and son analyzed with clinical and laboratory findings, and reasons of the short stature in Williams-Beuren syndrome are discussed through the literature.

Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the pancreatic beta cell, are identified in approximately 50% of these patients. The first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can be used in patients who show no response to diazoxide. Nifedipine, a calcium-channel blocker, has been shown to be an effective treatment in a small number of patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months of age due to a lack of response to diazoxide and octreotide treatment. Severe hypoglycemic attacks continued following surgery, while the patient was being treated with octreotide. These attacks resolved when nifedipine was introduced. Whilst our patient responded well to nifedipine, the dosage could not be increased to 0.75 mg/kg/day due to development of hypotension, a reported side effect of this drug. Currently, our patient, now aged 4 years, is receiving a combination of nifedipine and octreotide treatment. He is under good control and shows no side effects. In conclusion, nifedipine treatment can be started in patients with HH who show a poor response to diazoxide and octreotide treatment.

Background and Aim: Accelerated weight gain after (adeno)tonsillectomy has been reported in a number of studies. Whether (adeno)tonsillectomy is also a risk factor for development of overweight is unknown. We investigated serum leptin and plasma ghrelin levels before and 1 year after (adeno)tonsillectomy operation in children., Materials and Methods: We studied 31 patients and 29 age- and sex-matched healthy control children. Auxologic evaluation and biochemical investigations were performed before surgery and 1 year later., Results: One year after surgery, height SDS (p = 0.001) and weight SDS (p = 0.004) were significantly increased in both groups. No changes in BMI SDS (p = 0.105) were observed. Preoperative leptin levels were significantly higher in patients than controls (p < 0.001). IGF-1, IGFBP-3, HOMA-IR and ghrelin values were not significantly different between the groups. One year after surgery, IGF-1 (p = 0.001) and IGFBP-3 (p = 0.001) were significantly increased, while ghrelin (p < 0.001) was significantly decreased. Postoperative leptin levels of patients were also significantly higher than preoperative values (p = 0.036)., Conclusion: Significantly higher leptin levels in patients compared to control both before and 1 year after an obstruction-relieving surgery suggested that higher levels might be due to leptin resistance in these patients. Based on our findings we recommend measurement of leptin levels longitudinally for at least 5 years after adenotonsillectomy.

We report a patient with a de novo telomeric association between chromosomes 19 and Y in conjunction with mixed gonadal dysgenesis. The patient was first admitted to the clinic because of abnormal external genitalia. Laparoscopic evaluation revealed (1) a rudimentary uterus, one fallopian tube, and a small gonad resembling an ovary on the right side, and (2) an immature fallopian tube, a vas deferens, and a gonad resembling a testis on the left side. Conventional cytogenetic analysis performed on cultivated peripheral blood cells, and tissue obtained from the phallus and a gonadal structure which resembled a testis revealed two different cell lines with the 46,X,tas (Y;19)(p11.3;q13.4) and 45,X karyotype. Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, b, c, or SRY regions on the long arm of the Y chromosome. This is the first report of a patient with mixed gonadal dysgenesis that is accompanied by a telomeric association between chromosomes 19 and Y with 45,X mosaicism.

Patients with DAX-1 gene mutations on chromosome Xp21 usually present with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Yet, neither correlation between the type of mutation and the age of onset of the disease nor mechanism of the mutation on puberty is fully understood. Here, we report a novel non-sense p.Gln208X mutation in the amino terminal domain of the DAX-1 gene observed in a large family with three boys presenting with adrenal manifestations at different ages. Furthermore, two boys developed spontaneous puberty that failed to progress at similar ages, whereas the other boy developed precocious puberty at 10 month of age. The unique structure of the DAX-1 gene may explain this phenotypic variability. However, more studies are needed to understand the role of the DAX-1 gene on development of the adrenal gland and hypothalamus-pituitary-gonadal axis.

X-linked hypophosphatemic rickets (XLH) is the most common inherited rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in 10 patients from 6 unrelated Turkish families by PCR-sequence analysis. Six different PHEX mutations were detected in the patients. Four of them were novel: c.1217G>A (p.C406Y) in exon 11, c.2078G>T (p.C693F) in exon 21, a splice donor site mutation in intron 13 (IVS13+1G>T), and a splice acceptor site mutation in intron 13 (IVS13-2A>G). De novo PHEX mutations were found exclusively in female patients from 4 families and inherited mutations were detected from remaining two families. The patients' phenotype was consistent with the loss of PHEX function. Literature review of 78 sporadic cases shows that de novo mutations are present in 83% female patients and female/male ratio is 5 to 1. One patient had biallilic PHEX mutations at c.1735G>A (p.G579R) whereas her mother and two siblings carried a monoallelic mutation. The clinical and laboratory findings of the patient with biallilic PHEX mutation were similar to those with monoallelic mutation. The study shows that PHEX mutation is a common cause of either familial or sporadic hypophosphatemic rickets in Turkish population. Gene dosage effect is not observed. The frequent de novo mutations found in the female patients are likely resulting from mutagenesis of X chromosome in paternal germ cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Context: Vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700) is a rare autosomal recessive disorder and is caused by mutations in the CYP27B1 gene., Objectives: We aim to investigate CYP27B1 mutation in seven patients from four separate families and characterize the genotype-phenotype correlation., Methods: The entire coding region of the CYP27B1 gene was sequenced, and genotype-phenotype correlation among patients was assessed., Results: Sequencing analysis identified biallelic CYP27B1 mutations in all patients and monoallelic mutations in their parents. One patient from the first family was compound heterozygous for c.1166G>A (p.Arg389His) and a novel nonsense mutation c.1079 C>A (p.Ser360*). Two patients from the second family were homozygous for a novel splice donor site mutation in intron 1 (c.195 + 2 T>G), causing partial retention of the intron and a shift in the reading frame. Both novel mutations lead to the complete loss of vitamin D1α-hydroxylase activity. Four patients from families 3 and 4 were homozygous for a previously reported duplication mutation in exon 8 (1319-1325dupCCCACCC, Phe443Profs*24). Interestingly, one patient who was presented with severe hypocalcaemia and seizures at 4 months of age as a result of Phe443Profs*24 has improved spontaneously since 11 years of age and does not need regular treatment. Her laboratory tests showed normal serum calcium and 1,25(OH)(2) D after refusing to take medication for 12 months., Conclusions: There is a good genotype-phenotype correlation in VDDR-IA. However, some patients may recover from the loss of CYP27B1 function, probably due to 1α-hydroxylase activity exerted by a non-CYP27B1 enzyme., (© 2012 Blackwell Publishing Ltd.)

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by early-onset diabetes, spondyloepiphyseal dysplasia, tendency to skeletal fractures secondary to osteopenia, and growth retardation. Mutations in the eukaryotic translation initiation factor 2α kinase (EIF2AK3) gene are responsible for this disorder. Here, we describe a boy with neonatal diabetes, diagnosed at 2 months of age, who developed severe growth retardation and a skeletal fracture during the follow-up period. The patient's skeletal X-ray revealed findings of skeletal dysplasia. A clinical diagnosis of WRS was confirmed by the identification of a novel homozygous nonsense mutation (R491X) in exon 9 of the EIF2AK3 gene. The aim of this report is to raise the awareness for Wolcott-Rallison syndrome in cases presenting with isolated neonatal diabetes. This patient demonstrates that the other findings of this syndrome might be obscured by a diagnosis of isolated neonatal diabetes.

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

Homozygous mutations in the glucokinase gene (GCK) result in a complete deficiency of the GCK enzyme, which leads to permanent neonatal diabetes mellitus. Whilst there has been one report of a patient (with a homozygous p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases were diagnosed with diabetes within the first 2 weeks of life. We now report a second unrelated patient with the same p.T168A GCK mutation who was diagnosed with diabetes at the age of 9 months. We conclude that the specific GCK mutation, as yet unidentified genetic modifiers, and/or environmental factors might have different effects on pancreatic beta-cell functions, causing variability in the age at diagnosis of diabetes.

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.

The objective was to determine molecular genetic analysis of the TPO gene in Turkish children with iodide organification defect (IOD). Patients with a diagnosis of primary hypothyroidism were evaluated. Subjects having a definite diagnosis of autoimmune thyroiditis, thyroid gland dysplasia and, or iodine deficiency were excluded. A total of 10 patients from nine unrelated Turkish families, with an unknown etiology of hypothyroidism, and with a presumptive diagnosis of IOD were included in the study. A perchlorate discharge test (PDT) was performed to all subjects, and sequence analysis of TPO gene was applied in patients with a positive PDT. Five out of 10 patients have a total IOD, while the five remaining patients have a partial IOD according to PDT results. In two sisters, one has a partial and the other one has a total IOD a novel homozygous nonsense p.Q315X mutation was found in exon 8. Additionally, a previously known homozygous missense p.R314W mutation was detected in the same exon in another patient with a total IOD. No TPO gene mutation was detected in any of the seven remaining patients. Two different TPO gene mutations were found to be responsible for IOD in two unrelated Turkish families from the same ethnic background. More subjects should be screened for detecting the prevalence and spectrum profile of TPO mutations in our population that might be helpful for understanding the pathophysiology of congenital hypothyroidism.