Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3β-Hydroxysteroid Dehydrogenase Deficiency

Trine H. Johannsen, Delphine Mallet, Harriet Dige-Petersen, Jørn Müller, Katharina M. Main, Yves Morel, Maguelone G. Forest
2005 Journal of Clinical Endocrinology and Metabolism  
Classical 3␤-hydroxysteroid dehydrogenase (3␤-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3␤-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17␣-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical
more » ... ted a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3␤-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly ele-vated ⌬ 5 -steroids, in particular 17␣-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated ⌬ 5 -/⌬ 4 -steroid ratios. Sequencing of the type II 3␤-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17␣-hydroxyprogesterone were found on blood spots from Guthrie's test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3␤-HSD gene. Because neonatal diagnosis could have prevented lifethreatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology. (J Clin Endocrinol Metab
doi:10.1210/jc.2004-1374 pmid:15671104 fatcat:j3cvkxlotfbtdegyozjsfpwspm