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| |  CYP21A2 Mutation Analysis Shows No Genotype-Phenotype Correlation in Adults With Congenital Adrenal Hyperplasia: Presented at ENDO 09 By Crina Frincu-Mallos, PhD WASHINGTON, DC -- June 17, 2009 -- In adults with congenital adrenal hyperplasia (CAH), no significant associations exist between genotype and physical characteristics, as shown by a genetic analysis presented here at the Endocrine Society's 91st Annual Meeting (ENDO 09). This study addressed the lack of data in adult CAH patients, said Nils Krone, MD, Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, United Kingdom. Dr. Krone presented data on June 11 pertaining to the genetic analysis of the United Kingdom cohort participating in the Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE), including adults with CAH seen at 17 endocrine tertiary care centres. This analysis focused on defects of the steroid 21-hydroxylase (CYP21A2), known to affect only adrenal steroidogenesis. CYP21A2 mutation analysis was performed in 153 patients (103 women, 50 men), with a median age of 35 years (range, 18-69 years). The analysis revealed that a large percentage of the patients with CAH (88%) carried a common CYP21A2 mutation on both alleles. In addition, the investigators identified 6 rare known mutations (H62L, L308F, R426H, R426C, R435C, R483P) and 5 novel mutations (R124C, Q141X, fs ex8 [2040delG], IVS9+1G>C, fs ex10 [2674dupC]). For the purpose of this analysis, patients were classified into established CYP21A2 mutation groups: Null (n = 33), A (n = 41), B (n = 35), C (n = 33), and D (n = 11). The current use of fludrocortisone, concurrently with elevated plasma rennin, was reflected in the salt-wasting CAH: 100%, 95%, 66%, and 42% of patients in groups Null, A, B, and C, respectively. Raised renin without fludrocortisone treatment was found in 6%, 15%, 26%, and 12% of patients in these groups, respectively. "Fludrocortisone use is imprecisely correlated with genotype and salt-wasting status," according to Dr. Krone. Across groups, the patterns of prescribed glucocorticoid were similar, with prednisolone being the most common (40%), followed by hydrocortisone and dexamethasone (each 23%). The daily use of glucocorticoid was highest in the Null group and lowest in group C, after adjusting for sex. There were no significant associations between genotype and height or body mass index (BMI), except for higher BMI in group A men compared with Null and lower height for women in group B. The investigators concluded that differences in underlying genotype cannot be linked to unsatisfactory outcomes in adults with CAH, which may be related to other factors such as steroid therapy. Further studies are needed to determine whether a therapeutic approach tailored to distinct mutation groups could help to optimize CAH management. Funding for this study was provided by The Society for Endocrinology and the Clinical Endocrinology Trust.
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