Lipoid adrenal hyperplasia caused by earlier unknown 21STAR gene mutations

Abstract

Lipoid adrenal hyperplasia (LAH) is a most severe type of congenital adrenal cortical dysfunction (CACD). In this type of CACD, there is defect in the conversion of cholesterol to pregnenolone, as a consequence the production of all steroid hormones was impaired in both the adrenals and gonads. Defects of the STAR gene encoding for a steroidogenic acute regulatory (StAR) protein underlie the disease in most cases. Until the present time, there have been no reports on cases of LAH in the Russian literature. The diagnosis of LAH was established by the authors in three genetic girls aged 2.3 years, 6 and 7 months who had a normal structure of the external genitalia and in whom the disease was marked by manifestations of primary hypoadrenocorticism at the age of 21, 2, and 10 days, respectively. A hormonal study failed to show elevated levels of Cortisol and 17-hydroxyprogesterone in response to adrenocorticotropic hormone stimulation. A molecular genetic study revealed the following STAR gene defects: P129AC/W250X, IVS5-1G, and W147X, respectively. Р129ЛС, IVSS, and W147X mutations have not been earlier described. The data of the observation emphasizes the need of including LAH into the algorithm of differential diagnosis of CACD in children with the normal female structure of the external genitalia. The molecular genetic analysis should be prominent in diagnosing LAH, by taking into account the lack of hormonal markers of the disease.