Adrenal Agenesis and X-Linked Adrenal Hypoplasia Congenita in A Toddler - A Case Report and Review of Literature

Adrenal agenesis (AA) and X-linked adrenal hypoplasia congenita are very rare anomalies. NROB/DAX-1 gene which is located on the X chromosome is associated with adrenal hypoplasia. Primary adrenal insufficiency and hypogonadotropic hypogonadism are the typical presentations. Here, we present a case of a two-year-old toddler who presented with hypoglycaemic convulsion, persistent hypotension, and generalised hyperpigmentation. His serum adrenocorticotropic hormone level was significantly raised while serum cortisol and 17- hydroxyprogesterone were within normal limits. Whole exome sequencing revealed a hemizygous single base pair deletion in exon 1 of the NROB1 gene located on the chromosome X (chrX:g.30308863del; Depth:84x) that results in a frameshift and premature truncation of the protein 95 amino acids downstream to codon 169 (p.Gly169AlafsTer95; ENST00000378970.5). He was diagnosed with adrenal agenesis and X-linked adrenal hypoplasia congenita. He was treated with oral steroid replacement therapy (hydrocortisone and fludrocortisone) and salt supplementation. On follow-up, hyperpigmentation was significantly decreased and growth was improved. This report emphasizes the importance of clinical vigilance and the role of genetic diagnosis in preventing severe adverse outcomes with primary adrenal insufficiency.