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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.

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.