ESPE Abstracts

Introduction: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder caused by impairment of one of the enzymes involved in the steroidogenesis pathway. 3βhydroxysteroid dehydrogenase type 2 deficiency (3βHSD2 deficiency) is a rare form of CAH (<0.5%) due to pathogenic variants in the HSD3B2gene encoding for the enzyme Type 2 3β-hydroxysteroid dehydrogenase Δ⁴–Δ⁵isomerase (3βHSD2).

Case presentation: A 15-day old female neonate was referred from a local hospital to the Pediatric Department of "G. Gennimatas" Hospital of Thessaloniki due to dehydration with hyponatremia and hyperkalemia, and hypertrophy of clitoris and labia majora. The patient was the first child of consanguineous parents originated from Afghanistan, now living in Greece. The biochemical and hormonal profile of the proband was consistent with CAH (17OHP: 69.5ng/ml, Cortisol: 3.9μg/dl, ACTH: 621pg/ml, Potassium: 7.1 mmol/l, Sodium: 123 mmol/l, Testosterone: 309ng/dl, DHEAS: >1500μg/dl, Androstenedione: 18.9ng/ml, Plasma Renin Activity: 40.4ng/ml/h and Aldosterone: 289 pg/ml). She was immediately commenced on hydrocortisone (15mg/m²/day) and fludrocortisone (200mg/day) with a good response. Molecular analysis was obtained.

Methods: PCR and bidirectional sequencing for the CYP21A2, CYP11B1and HSD3B2genes was carried out sequentially in the Laboratory of Molecular Endocrinology, First Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, “Agia Sophia” Children’s Hospital. MLPA analysis was also performed for the identification of Copy Number Variations (CNVs) in the CYP21A2gene (P050-C1 CAH).

Results: Molecular investigation of the CYP21A2gene revealed that the index patient carried the Q318X pathogenic variant on a duplicated CYP21A2gene in heterozygosity. Analysis of the parents showed that they were also carriers of the p.Q318X pathogenic variant on a duplicated CYP21A2gene in heterozygosity. No pathogenic variants were detected in the CYP11B1gene on the index patient. Analysis of the HSD3B2gene revealed a homozygous 2bp deletion at codon 273 (p.[Lys273fs];[Lys273fs]). The parents were found to harbor the p.Lys273fs in heterozygosity.

Discussion: We herein present a patient with a homozygous deletion in the HSD3B2gene. This variant has already been reported in homozygosity in 3 male patients with severe salt wasting CAH (2 of them originated from Afghanistan and 1 from Pakistan). To our knowledge, this is the first female patient presented with the homozygous p.Lys273fs deletion in the HSD3B2gene. Another female patient has been reported with the p.Lys273fs variant in compound heterozygosity with p.Thr318fs variant, presenting pigmentation and mildly enlarged clitoris at birth. Molecular investigation is important in order to confirm the clinical diagnosis and provide proper treatment and genetic counseling to the family.