ESPE Abstracts

Background: In adrenal gland 3β-HSD₂ catalyses the conversion of Δ⁵ to Δ⁴ steroids (i.e., pregnenolone to progesterone,17 α-hydroxypregnenolone to 17-OHP and DHEA to androstenedione). Defect in this enzyme can affect glucocorticoid, mineralocorticoids and sex steroid synthesis but the clinical and biochemical profile can be very complicating and confusing due to conversion of intermediate steroids to more active steroids by 3β-HSD ₁in peripheral tissues. Children typically present with ambigious genitilia. Boys (46xy) tend to have sever hypospadias and small phallus with variable degree of salt loss. Girls (xx) can present ranging from mild clitoromegaly to completely normal female genitilia. Mild variety can present with premature adrenarche, hirsutism. In our case series we will present genetically confirmed (HSD3β₂) mutations with very variable and confusing presentations with multiple deaths in families due to late diagnosis.

Case Summaries: We identified 6 patients (4 male) from 3 families of CAH due to 3βHSD₂deficiency variant of c.818_819del p.(Lys273Argfs*7) born to consanguineous parents with history of sibling death in 2 families. Family 1 had 5 sibling death (2 female and 3 male) and family 2 had 1 sibling death (male). All presented within neonatal life (7 – 45 day of life) with failure to thrive and vomiting. Female patients were having normal genitalia at presentation, while 3/4 male presented with mild genital ambiguity (under-virilization) and 1/4 with normal male genitalia. Initial workup of all revealed significant hyponatremia, hyperkalemia and raised renin. 17-OH progesterone was initially raised in 5 cases. DHEASO4 (normal) and cortisol (low) was done only in 2 cases due to non-affordability. After initial stabilization with hydration and stress dose of hydrocortisone, all were started on maintenance dose of hydrocortisone (15mg/m²/day) and fludrocortisone (0.1 mg daily) along with sick day education.

Conclusion: CAH patients due to 3βHSD₂deficiency can present with normal male or female genitalia. We need to have a strong suspicion of it in region where there is increase consanguinity and no screening tests, to avoid preventable deaths due to this variant.