Cholesterol supplementation enhances growth of phallus in Smith-Lemli-Opitz syndrome

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol biosynthesis due to a deficiency of the last enzyme of the cholesterol synthetic pathway, 7-dehydrocholesterol reductase. Affected patients have low concentrations of cholesterol and elevation of the cholesterol precursor, 7-dehydrocholesterol (7-DHC). Multiple congenital anomalies, dysmorphic facies, and growth and developmental retardation are common. Severely affected males have ambiguous genitalia. We believe that the genital anomalies seen in affected males are due to deficiency of androgens, but this has never been proven.

The infant was diagnosed prenatally with SLOS by sterol analysis of amniotic fluid at 30 weeks gestation. Physical examination on Day 1 of life revealed many of the physical features of SLOS. Biochemical studies confirmed the prenatal diagnosis. The penis measured 1 × 0.7 cm, and was hooded and ventrally bound. He had a third-degree hvpospadias and a bifid scrotum. There was hyperpigmentation of the nipples and scrotum.

Treatment with exogenous cholesterol (150 mg/kg/day) resulted in an increase in the size of the phallus to 2.3 × 1.2 cm in six weeks. Biochemical studies before and after therapy revealed the following cholesterol of 21.8 and 26 mg/dl, 7-DHC of 7.25 and 12 mg/dl; ACTH of 150 and 77 pg/ml; cortisol of 9.6 and 14 mcg/dl; testosterone of 48 and 153 ng/dl; and dihydrotestosterone of less than 2 and 38 ng/dl.

We conclude that in males with SLOS treatment with cholesterol improves biosynthesis of cortisol and androgens, and enhances phallic growth.