Suttipong Wacharasindhu

Identification of mutations in the SRD5A2 gene in Thai patients with male pseudohermaphroditism.

OBJECTIVE To describe two unrelated Thai patients with suspected 5alpha-reductase type 2 deficiency and perform mutation analysis of the SRD5A2 gene. DESIGN Case report. SETTING A pediatric endocrinology clinic at a university hospital. PATIENT(S) Two unrelated patients with 46,XY karyotype, born with ambiguous genitalia, were studied. One was reared as a boy and the other was reared as a girl. INTERVENTION(S) The entire coding regions of the SRD5A2 gene were assessed by polymerase chain reaction (PCR) and sequencing analysis. MAIN OUTCOME MEASURE(S) Molecular characterization of the SRD5A2 gene. RESULT(S) Four different pathogenic mutations (three missense and one nonsense) were identified. These were located at exon 1 (p.Q6X and p.L20P), exon 3 (p.G183S), and exon 4 (p.G203S). The T>C transition (c.59T>C) resulting in a leucine-to-proline substitution at codon 20 (p.L20P) has not been previously described and was not detected in 100 unaffected, ethnic-matched control chromosomes. In addition, p.G183S, previously identified only among patients from mixed African-European ancestry and in the Dominican Republic, was also detected in a Thai patient. CONCLUSION(S) This study demonstrates that the SRD5A2 gene is responsible for 5alpha-reductase type 2 deficiency across different populations and emphasizes the important role of genetic testing for the definite diagnosis and genetic counseling before gender assignment or any surgical intervention.

A Girl with a Novel Splice Site Mutation in VDR Supports the Role of a Ligand-Independent VDR Function on Hair Cycling

Mutations in vitamin D receptor (VDR) cause hereditary vitamin D resistant rickets (HVDRR). We reported a Thai girl with HVDRR, presenting with an early onset of rickets and partial alopecia. She was a product of a consanguineous couple. Mutation analysis showed that she was homozygous for a novel splice site mutation of the VDR gene, 462 + 1 G → C, resulting in incorporation of the whole 254 bp of the intron 4 into its mRNA. The mutated protein is expected to contain no ligand-binding domain. The fact that she did not develop total alopecia despite of no VDR ligand-binding domain supports that VDR function on hair cycling is ligand independent.

Expanding clinical spectrum of non-autoimmune hyperthyroidism due to an activating germline mutation, p.M453T, in the thyrotropin receptor gene

Objective  To describe clinical and genetic features of a Thai family with non‐autoimmune hyperthyroidism (NAH) caused by an activating germline mutation in the thyrotropin receptor (TSHR) gene.

Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty.

Abstract Background: Reports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty. Methods: A cross-sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL. Results: The median adjust-BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 μg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 μg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 μg/g Cr: p=0.09), but not statistically significant. Conclusions: The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls.

Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus

Objective To describe a Thai girl with congenital nephrogenic diabetes insipidus (NDI) and perform mutation analysis of the AQP2 gene. Design: Case report. Patient A 6-year old girl with a history of failure to thrive, polydipsia and polyuria was studied. Polyuria and polydipsia were observed within the first few months of life. Despite normal serum osmolality and electrolyte, the result of water deprivation test was compatible with a diagnosis of NDI. Methods The entire coding regions of the AQP2 gene were assessed by polymerase chain reaction and sequencing analysis. The presence of mutations was also confirmed by restriction enzyme digestion analysis. Results Two heterozygous novel missense mutations were identified. Both were located in exon 1; a guanine-to-thymine substitution at nucleotide position 3 (c.3G→T) inherited from her mother and a guanine-to-adenine at position 85 (c.85G→A) inherited from her father, resulting in a methionine to isoleucine at codon 1 (p.M1I) and glycine to serine at codon 29 (p.G29S), respectively. These mutations have never been previously described and were not detected in 100 ethnic-matched unaffected control chromosomes. Conclusion We report two novel mutations of the AQP2 gene, p.M1I and p.G29S, associated with autosomal recessive congenital NDI. This study expands the genotypic spectrum of AQP2 mutations and emphasizes an important role of genetic testing for definite diagnosis and genetic counseling.

DKA with Severe Hypertriglyceridemia and Cerebral Edema in an Adolescent Boy: A Case Study and Review of the Literature

A 13-year-old adolescent boy with type 1 diabetes mellitus (1b) presented with diabetic ketoacidosis (DKA) and cerebral edema. Grossly lipemic serum and lipemia retinals due to extremely high triglyceride (TG) level were observed without evidence of xanthoma or xanthelasma. Cerebral edema was treated by appropriate ventilation and mannitol administration. Normal saline was carefully given and regular insulin was titrated according to blood sugar levels. Triglyceride levels were reduced from 9,800 mg/dL to normal range within 9 days after conventional treatment was commenced without antilipid medication. Based on our review of the literature, this is the first reported case of confirmed pediatric DKA with severe hypertriglyceridemia and cerebral edema. In patients with DKA and hypertriglyceridemia, clinicians should be mindful of the possibility of associated acute pancreatitis and cerebral edema.

Original article. Trends and characteristics of childhood diabetes in a tertiary care center in Thailand

Abstract Background: Reports on characteristics of pediatric diabetes in children from Southeast Asian countries are limited. Objectives: To describe the clinical characteristics, prevalence, glycemic control, and current treatment regimens of diabetes in Thai children. Materials and Methods: Data from 132 patients seen at our pediatric diabetes clinic at Chulalongkorn University during 2001−2013 were retrospectively reviewed. Results: We found an increasing number of patients newly-diagnosed with type 1- (T1DM) or type 2- diabetes mellitus (T2DM). The overall proportion of T1DM was 69.7%, T2DM 23.4%, and other types 6.9%. Children with T1DM were younger at diagnosis, had higher initial glucose and glycated hemoglobin A1c (HbA1c), a lower body mass index z-score, lower C-peptide and insulin levels, and were more likely to have classic diabetes symptoms and ketoacidosis, compared with children with T2DM. Mixed diabetes phenotypes were found in about 12%−14% of these children. Glutamic acid decarboxylase and islet antigen-2 autoantibodies were found in 70% and 54% of T1DM patients, respectively, and not in T2DM patients. HbA1c in T1DM was 9.6 ± 2.2% total hemoglobin, and in T2DM was 7.9 ± 2.6%. There were no differences in HbA1c levels between different insulin regimens in the T1DM group. Conclusion: The number of children with T1DM or T2DM has been increasing and there are overlapping phenotypes in a significant proportion of these children. Correct diagnosis requires clinical evaluation and monitoring of the clinical course. Further research is needed to determine the risk factors for the poor glycemic control found in children with T1DM.

Endocrine Abnormalities in Patients with Frontoethmoidal Encephalomeningocele

Background: Frontoethmoidal encephalomeningocele (FEEM) is a congenital neural tube defect which is more common in Southeast Asia. Its etiology is unknown. No one has ever reported endocrine abnormalities in this condition. Method: We retrospectively reviewed medical records of 84 patients with FEEM, primarily focused on the clinical data suggestive of endocrine disorders including growth parameter, thyroid function test, serum electrolyte and serum osmolality. Results: Nasoethmoidal was the most common subtype found in this study. Sixty-four percent of our patients had their heights below the mean height of normal Thai children. The incidence of hypothyroidism (1:28), central DI (1:42) and GHD (1:42) were higher than that in the general population. Conclusion: A significant number of patients with FEEM had clinical evidences suggestive of hypothalamopituitary insufficiency. Appropriate replacement therapy is mandatory in order to prevent untoward complications.

Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

Abstract Background: Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. Methods: We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. Results: We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose >155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤155 mg/dL. Conclusions: Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of >155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

Pubertal growth in normal Thai children: a longitudinal study

Abstract Background: Pubertal growth data in Thai children has been reported as cross-sectional studies. There is no longitudinal study in Thai children. Objective: Investigate the longitudinal growth data in normal Thai children including the relationship between age at pubertal onset and other growth parameters. Material and method: Eighty-eight normal children (44 boys, 44 girls) were longitudinally assessed for the growth and puberty until they reached their final adult height. Pubertal staging was assessed by the Tanner method. Results: Mean age of pubertal onset was 10.2 ± 1.2 years for girls and 12.2 ± 1.0 years for boys. Total pubertal height gain was 18.3 ± 4.0 cm for girls and 22.3 ± 4.4 cm for boys. Total pubertal height gain had a negative correlation with age at pubertal onset for girls, but not for boys. Conclusion: The onset of puberty was not much changed from previous studies. Girls with early puberty had a higher pubertal height gain. This might be due to a compensatory mechanism. These longitudinal growth data can be used as a reference in clinical practices for Thai children.