STAR mutations causing non-classical lipoid adrenal hyperplasia manifested as familial glucocorticoid deficiency

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by single cortisol deficiency but normal aldosterone and renin levels. Beginning from the discovery of the disease to that of the pathogenic genes over a period of 30 years, the development of gene detection technology has identified a large number of FGD-related genes. Despite the fact that the genetic defect underlying this disease is known for approximately 70% of the patients diagnosed with FGD, there are still several unknown factors causing it. FGD is divided into type 1, type 2 and non-classical type according to the mutant gene. The case described in the present study reported two patients, who were siblings, having skin hyperpigmentation and undergone treatment in adulthood. The gonadal development was normal and the proband had a 10-year-old son. Laboratory tests suggested glucocorticoid deficiency and a mild lack of mineralocorticoid, indicating hyponatremia and hypotension in the proband. In addition, cortisol deficiency was not affected by adrenocorticotropic hormone treatment, while the adrenal glands in the two patients did not show any hyperplasia. Gene analysis revealed two compound heterozygote mutations c.533T>A (p. Leu178Gln) and c.737A>G (p. Asp246Gly) in the steroid hormone acute regulatory protein (STAR) gene in both patients, which may have been obtained from their parents and the proband passed one of the mutations to her son. The present study results revealed that STAR mutations cause non-classic congenital lipoid adrenal hyperplasia in China.