ESPE Abstracts

Background: The StAR protein is crucial for the transportation of cholesterol to the mitochondria, where it is converted to pregnenolone. Complete loss of StAR protein function impairs adrenal and gonadal steroidogenesis since the fetal period, called classic lipoid adrenal hyperplasia (CLAH). Nonclassic lipoid adrenal hyperplasia (NCLAH) is a recently recognized disorder, with partial StAR protein function, and several mutations causing NCLAH have been reported.

Objective: To report clinical, biochemical, genetic, and functional data on a mutation of the STAR gene.

Patient: A Japanese boy was born with normal male genitalia, and had hyperpigmentation. At 2 years of age, he experienced an episode of adrenal failure accompanied by infection, and his medical history was uneventful before this. Serum cortisol was undetectable, and did not respond to ACTH stimulation. Aldosterone showed a low response in the furosemide-upright test, and a CT scan showed normal-sized adrenal glands. At 11 years of age, he had normal pubertal development, but serum DHEA-S level was very low.

Methods: STAR genetic analysis was performed. The ability of STAR mutations on the conversion of cholesterol to pregnenolone was assessed.

Results: We identified compound heterozygous mutations K238fs and R272C. In vitro experiments showed that the R272C mutation retained 50% of the WT activity. Western blotting and visualization of mitochondria localization revealed no significant difference between the WT and the R272C mutant.

Discussion and conclusions: Our patient presented with adrenal failure at 2 years of age and normal male external genitalia. This phenotype may be related to residual StAR protein activity. The K238fs/Q258X mutation was previously reported in Japanese patients with CLAH, and the R272C/Q258X mutation was recently reported in a Japanese patient with primary adrenal failure without enzymatic defect. The frequency of these mutations may be high in Japanese patients.