A Case of X-Linked Adrenal Hypoplasia Congenital (AHC) Due to Large Deletion of NR0B1 (DAX1) and Contiguous Gene.

ABSTRACT

X-linked adrenal hypoplasia congenita (AHC) is caused predominantly by mutations in the NR0B1 (DAX1) gene. Among these, X-linked AHC due to a large deletion of NR0B1 is extremely rare. In Korea, the first case was reported in 2005, and there have been no further documented cases since then. Herein, we report a unique case of X-linked AHC caused by an entire gene deletion that includes the NR0B1 gene and seven other genes. A seven-day-old boy presented to a pediatric endocrine clinic with prolonged postnatal jaundice, skin hyperpigmentation, hyponatremia, and hyperkalemia, suggestive of an adrenal crisis. In genetic analysis, next-generation sequencing panel for congenital adrenal hyperplasia (CAH) showed no variants. However, chromosomal microarray results revealed large deletion of Xp21.2 (29,655,007_30,765,126) including eight protein-coding genes (NR0B1, IL1RAPL1, GK, MAGEB1-4, TASL). In cases of atypical adrenal insufficiency and genetically undiagnosed CAH, NR0B1-related AHC should be suspected, as Xp21 deletion is very rare and not detected in NGS, making microarray the best option for genetic diagnosis.