Abstract 51: Primary adrenal insufficency in children: A case report

Introduction: Primary adrenal insufficiency (PAI) is a life-threatening condition in children warranting a high index of suspicion. Although 21 hydroxylase deficiency accounts for the majority of PAI, many other inherited conditions have been reported presenting with a wide spectrum of presentations. Materials and Methods: Seven patients of PAI presenting to the Department of Endocrinology during the last one year were evaluated and classifiedbased on clinical, biochemical, and mutational analysis. Results: There was one male infant who presented with a bifid scrotum and perineal hypospadias due to 3β-Hydroxysteroid dehydrogenase 2 deficiency. Exome sequencing revealed a novel missense mutation in HSD3B2 gene, whose significance was strengthened in the context of a positive family history. Two infants (a male and a female) presented with salt losing crises at about nine months of age. Both had congruent phenotypic and genotypic features and extremely low levels of steroid metabolites alluding to a very proximal defect of steroidogenesis. Mutational analysis revealed homozygous missense variations in NNT gene leading to familial Glucocorticoid deficiency-4 requiring glucocorticoid as well as mineralocorticoid replacement. One child presented with crisis in the first week of life with undetectable steroid metabolites but was peculiar in that the karyotype was 47, XXY. Clinical exome sequencing revealed a missense mutation of the StAR gene. This case represents a complete sex reversal of a Klinefelter male due to Lipoid congenital adrenal hyperplasia. Another female child presented with asymptomatic hyperpigmentation at 18 months of age. She had undetectable steroid metabolites leading up to cortisol but normal aldosterone levels, explaining the absent salt wasting. Genetic analysis revealed homozygous missense variation in the MC2R gene causing familial glucocorticoid deficiency-1. One girl presented at 2 years of age with progressive clitoral enlargement and hypertension and was diagnosed with 11-beta- hydroxylase deficiency. Finally one boy presented at 6 years of age with neurodegeneration, blindness and hyperpigmentation. MRI brain suggested X linked adrenoleukodystrophy which was subsequently confirmed on next generation sequencing. Discussion: The wide spectrum of PAI in these children in a relatively short period of time suggests that the frequency of the causes as the etiology of PAI may be much more and molecular diagnosis has important translational impact for prenatal testing, early diagnosis, optimal treatment for these children and their families.