Background: Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by deficiency of various enzymes responsible for adrenal steroidogenesis. 11-Beta-hydroxylase deficiency (11βOHD) and17-hydroxylase/17,20-lyase deficiency (17OHD) are rare causes of CAH.
Methods/results: We hereby present a 65-year-old man with 11βOHD and a 33-year-old woman with 17OHD. The man with 11βOHD presented with peripheral precocious puberty and hypertension at age 15 years, fathered two children but developed complications of chronic glucocorticoid therapy on long-term follow-up. Interestingly, his younger sister had been diagnosed with the same condition at age 19 and had later given birth to four children while on glucocorticoids. Exome sequencing of the CYP11B1 gene detected the previously reported pathogenic mutation T318T (c.954G > A [p.Thr318Thr]) on one of the alleles and a novel mutation, R123G (c.367C > G [p.Arg123Gly]), on the other in a highly conserved region of the CYP11B1 gene. The woman with 17OHD presented with severe hypokalemia at age 22 years against a background of primary amenorrhea and lack of development of secondary sexual characteristics. She was heterozygous for a previously recognized mutation, R125Q (c.374G > A[p.Arg125Gln]), and a novel single base-pair deletion, G337fs (c.1010delG[p.Gly337Valfs*82]), which creates a frameshift with a new stop codon in the last exon of the gene, making it a likely pathogenic variant.
Conclusion: Recognition of novel mutations is clinically significant and will contribute to the understanding of the phenotype-genotype relationship of these rare disorders in the future. It also highlights successful fertility outcomes in 11βOHD which have not been well documented in the literature so far.