Mutations in CYP11A1, like those in STAR cause lipoid congenital adrenal hyperplasia manifesting with adrenal and gonadal insufficiencies along with derangements of the renin/angiotensin system. Increased adrenal size is usually a feature of STAR but not of CYP11A1 mutation. Milder forms presenting without all of these features have also been described. We present six patients from four families with CYP11A1 mutations discovered by whole exome sequencing. The mutations were as follows; two sisters had a homozygous A359V mutation, two siblings had compound heterozygous mutations I279Yfs*9;*122Rext*68, one patient was compound heterozygous for Q395K and R120Q and one was compound heterozygous for E314K and an exon 5/intron 5 splice site mutation. The presentation varied between cases, ranging from a patient with neonatal salt wasting/adrenal crisis and large adrenals to a pair of non-pigmented sisters aged 2 and 4y on glucocorticoid replacement alone. Whole exome sequencing revealed the nature of the underlying defects in all patients to be mutation(s) in CYP11A1, the gene encoding the first enzyme in the steroidogenic pathway, converting cholesterol into pregnenolone. These cases emphasize the utility of whole exome sequencing as a tool for improved diagnosis and therefore patient management in the endocrine clinic.
12 - 14 Nov 2014
British Society for Paediatric Endocrinology and Diabetes