Genotype-phenotype correlation of KATP channel gene defects causing permanent neonatal diabetes in Indian patients.

BACKGROUND: There are very few reports pertaining to Indian patients with neonatal diabetes mellitus (NDM). Activating or gain of function mutations of KATP channel genes namely KCNJ11 and ABCC8 are most predominant cause of permanent neonatal diabetes mellitus (PNDM). OBJECTIVES: To identify the genotype-phenotype correlation of KATP channel gene defects in a large series of (n = 181) Indian PNDM patients. METHODS: Direct sequencing of all exons of KCNJ11 and ABCC8 genes in all 181 patients with PNDM were performed. Clinical and biochemical data were collected. RESULTS: We have identified the molecular basis of KATP -NDM in 39 out of 181 patients (22%). Of these, 20 had KCNJ11 mutations and 19 had ABCC8 mutations, thus comprising 51% of KCNJ11 and 49% of ABCC8. There were four novel mutations (D1128Tfs*16, Y1287C, S1422T, and H1537R) in ABCC8 gene. Three patients with KCNJ11 mutations had developmental delay with DEND syndrome. In patients with ABCC8 mutations developmental delay was seen in seven out of 19 (36.8%). Of this, three patients (15.7%) had DEND phenotype and four (21%) had iDEND. Of the 39 patients, 33 (84%) patients were shifted to sulfonylurea therapy (glibenclamide). Of this, 19(57.5%) patients harbored KCNJ11 mutations and 14(42.1%) ABCC8 mutations. CONCLUSIONS: This is the first largest study in NDM patients in India demonstrating the importance of KATP channel gene mutation screening in PNDM and efficacy of glibenclamide for Indian patients with KATP -PNDM. The success rate of transfer is more in patients with KCNJ11 mutations compared with those with ABCC8 mutations.

Height Velocity Percentiles in Indian Children Aged 5-17 Years.

OBJECTIVE: To assess height velocity and develop height velocity percentiles in 5-17-year-old Indian children; and to study the magnitude and age at peak height velocity. DESIGN: Mixed longitudinal study. SETTING: Private schools at Pune and Delhi. PARTICIPANTS/PATIENTS: 2949 children (1681 boys) belonging to affluent class aged 5-17 years (1473-Pune, 1476-Delhi). METHODS: Annual height and weight measurements from 2007 to 2013. Total 13214 height velocity measurements (7724 on boys). OUTCOME MEASURES: Height velocity percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) constructed using LMS chart maker. RESULTS: Age- and gender-specific height velocity percentiles were generated. Median height velocity in girls decreased from 5 to 8 years, increased to a peak of 6.6 cm at 10.5 years and then declined to 0.3 cm at 17.5 years. In boys, median height velocity reduced till 10.5, increased to a peak of 6.8 cms at 13.5 years and then declined to 1cm by 18 years. CONCLUSIONS: Height velocity percentiles in 5-17-year-old urban Indian children were constructed.

Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases.

Background Triple A syndrome is characterized by achalasia, alacrima and adrenal insufficiency with neurological manifestations occurring later in the course of the disease. It occurs due to biallelic mutations in the AAAS gene which codes for the nuclear pore protein ALADIN. A number of other features have been reported over time in this heterogeneous and multisystemic disorder. Unlike other autosomal recessive disorders, triple A syndrome patients show a wide phenotypic variability both among different patients and family members harboring the same mutation(s). A gene-environment interaction has been thought to be a plausible cause. Methods A retrospective analysis of six families and seven patients presenting with triple A syndrome was carried out. The clinical, biochemical and molecular testing data were collected and correlated. The results of treatment and follow-up and genetic counseling of the families were obtained wherever feasible. Results Our cohort consisted mostly of children and displayed a wide phenotypic variability in the presenting symptoms ranging from hypoglycemic seizures at the severe end of the spectrum to insidious hyperpigmentation and delayed development. Neurological and autonomic features were present in a few patients, suggesting requirement of prolonged follow-up for these patients. A significant gap between the onset of symptoms and confirmatory diagnosis was noted, suggesting that a high index of suspicion is required for diagnosing this disorder. Sudden unexplained death was observed in siblings, and early diagnosis and treatment could help in preventing early mortality and improving the quality of life for these patients. Conclusion High index of suspicion for a potentially treatable disorder allows early appropriate intervention.

Waist circumference percentiles in 2-18 year old Indian children.

OBJECTIVES: To develop reference percentile curves in Indian children for waist circumference (WC), and to provide a cutoff of WC percentile to identify children at risk for metabolic syndrome (MS). STUDY DESIGN: A multicenter, cross-sectional study was performed in 5 major Indian cities. Height, weight, and blood pressure (BP) were measured in 10,842 children (6065 boys). Elevated BP was defined as either systolic BP or diastolic BP >95th percentile. WC was measured with the child standing using a stretch-resistant tape. Sex-specific reference percentiles were computed using the LMS method which constructs reference percentiles adjusted for skewness. To determine optimal cutoffs for WC percentiles, a validation sample of 208 children was assessed for MS risk factors (ie, anthropometry, BP, blood lipids), and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Age- and sex-specific WC percentiles (5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, and 95th) are presented. WC values increased with age in both the boys and the girls. The median WC at age >15 years was greater in boys compared with girls. ROC analysis suggested the 70th percentile as a cutoff for MS risk (sensitivity, 0.84 in boys and 0.82 in girls; specificity, 0.85 in both boys and girls; area under the ROC curve, 0.88 in boys and 0.92 in girls). CONCLUSION: Age- and sex-specific reference curves for WC for Indian children and cutoff values of 70th WC percentile for screening for MS risk are provided.

A unique case of dystrophic calcification in masseter: a diagnostic challenge.

The objective of this study was to present an unusual case of isolated dystrophic calcification in masseter and the diagnostic challenge it posed. A case report on a 14-year-old boy presented with swelling in left parotid region along with the review of literature was reported. Histopathological and biochemical analyses of the excised mass diagnosed this affliction as dystrophic calcification. Dystrophic calcification is deposition of calcium salt in degenerated tissues in the presence of normal calcium and phosphorous metabolism. It usually occurs in injured tissues. This is different from systemic mineral imbalance causing metastatic calcification and needs to be differentiated. On reviewing the literature, this appears to be the second reported case in the world wide literature. The unique presentation, diagnosis, and surgical management of dystrophic calcification have been described.

Small for gestation and growth hormone therapy.

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<-2SD) and do not achieve normal adult height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above -2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.