Clinical and molecular characterization of thirty Chinese patients with congenital lipoid adrenal hyperplasia

Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179−15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.