Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) has an estimated prevalence of one in 10 000–20 000 live births. Patients are described as salt wasting (SW), simple virilising (SV), or non-classical (NC). The CAH genotype is usually compound heterozygous.

Aims: To characterise the cohort of CAH patients presenting to a regional centre 1994–2014, to quantify the allelic frequency of CYP21A2 mutations and to examine genotype–phenotype associations.

Method: Retrospective notes review. Genotype according to mutational analyses performed at diagnosis using pyrosequencing, fluorescent PCR, and multiplex ligation-dependent probe amplification (MLPA). Phenotype determined by clinical presentation, age of presentation, 17-OHP levels, plasma renin, urinary steroid profile, and Synacthen tests.

Results: Using the regional endocrine database, 74 patients were identified (four had declined mutational analysis). Only four were non-Caucasian. 28 had a known family history. 48 presented within the first year of age. SW: total 47 (64%); 54% female; 85% presented <30 days. SV and NC: total 26 (36%); eight on glucocorticoid only and two on no long-term medication. The most common mutations in our cohort were the CYP21A2 chimeric deletion/conversion encompassing exons 1–3, c.290-13C>G, c.515T>A; p.Ile172Asn and c.841G>T; p.Val281Leu. Two SW patients were identified with the rarer mutations g.2578 C>T (p.Pro453Ser) and exon 6 cluster (p.Ile236Asn, pVal237Glu, and pMet239Lys). c.290-13C>G and c.515T>A; p.Ile172Asn were most common in SW patients, despite usually being associated with the SV form. c.841G>T; p.Val281Leu was associated with SV CAH, especially milder disease.

Conclusions: We characterise a cohort of CAH patients from a defined region of the UK with a relatively static population. Our work supports previous findings that a small number of mutations are commonly associated with CAH, while indicating a need to reconsider some established genotype–phenotype correlations. We report interesting rarer mutations. Improved understanding of genotype-phenotype correlation will have implications for management, genetic counselling, and prenatal diagnosis.