Background: 3β-hydroxysteroid dehydrogenase (3βHSD) deficiency is a rare form of congenital adrenal hyperplasia (CAH) and caused by loss of function mutations in the HSD3B2 gene. In classic form, affected patients have salt wasting early in infancy and may have ambiguous genitalia in both sexes. Herein we report a nonvirilized female patient with classic form of 3βHSD deficiency due to homozygous S218P mutation in the HSD3B2 gene and classic phenylketonuria.
Case report: A female neonate was born after uneventful pregnancy by spontaneous vaginal delivery. The parents were first degree cousins. Phenylalanine level was elevated in newborn screening so she was diagnosed with classic phenylketonuria and was put on phenylalanine restricted diet at 7 days of age. At one month of age she was found to be lethargic and dehydration, she failed to gain weight. Laboratory results showed severe hyponatremia (Na: 119 mEq/l), hyperkalemia (K:7 mEq/l), normal glucose level. ACTH was 926 pg/ml, cortisol: 7.3 μg/dl, renin: 1205 pg/ml, aldosterone: 1089 pg/ml, testosterone: 216 ng/dl; androstenedione: >10 ng/ml; 17OHP: 105 ng/ml; 11 deoxycortisol: 132 ng/ml; DHEAS: 1387 μg/dl so she was diagnosed with CAH. In spite of dramatically elevated androgen levels she did not have any sign of virilisation. The karyotype was 46,XX. Pelvic ultrasonography revealed normal female internal genitalia. Mineralocorticoid and glucocorticoid replacement was started. Genetic tests confirmed the diagnosis of 3βHSD deficiency due to homozygote mutation in the HSD3B2 gene (S218P). CYP21A2 and CYP11B1 genes were normal.
Conclusion: Homozygous S218P mutation in the HSD3B2 gene was associated with nonvirilization of external genitalia in our patient. Previously a compound heterozygous Y190C and S218P mutations has been reported in a girl with moderate virilization. Data is not sufficient for a genotype-phenotype correlation for the current mutation yet.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology