We characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory results. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The enzymatic block was found at the beginning of steroidogenesis. The mutation was confirmed in the CYP11A1 gene. The patient is compound heterozygote for the novel CYP11A1 missense mutation >A () in exon 2 and frameshift mutation _509delCT (*30) in exon 3. The CYP11A1: >A () was predicted as pathogenic by in silico analysis. So far, only 19 patients with CYP11A1 mutations causing P450scc deficiency have been reported worldwide. There are no related reports in the Czech Republic.
In a 46,XY phenotypic female, born at term to healthy consanguineous parents, who presented relatively late at the age of 1 year 9 months with life-threatening adrenal insufficiency and complete sex reversal ( 613743 ), al Kandari et al. (2006) identified homozygosity for a C-to-T transition in exon 6 of the CYP11A1 gene, resulting in an ala359-to-val (A359V) substitution. The patient was also found to have complete agenesis of the corpus callosum. Functional analysis of the mutant enzyme revealed markedly reduced enzyme activity, with about 11% residual activity. The parents were heterozygous for the mutation.