A NOVEL MUTATION ASSOCIATED WITH NON-CLASSICAL CONGENITAL ADRENAL HYPERPLASIA IN AN EMIRATI FEMALE

Abstract

BACKGROUND
Deficiency of the steroid 21-hydroxylase, encoded by CYP21A2 gene, accounts for 95-99% of all congenital adrenal hyperplasia (CAH) cases. We report a case of non- classical CAH (NCAH) due to a novel CYP21A2 mutation with unusual biochemical features.

CASE
A 24-year-old Emirati female with a BMI of 25.72 kg/m2 presented with a history of repeated pregnancy losses (RPL) of spontaneous and in-vitro fertilization (IVF) pregnancies, hair fall and irregular menstrual cycles. She had acne, hirsutism, autoimmune thyroiditis and a thyroid nodule which were duly addressed. Biochemical tests showed very high levels of 17-OH progesterone (1071 ng/dL); however, testosterone, DHEAS and androstenedione levels were normal. Ovarian ultrasound showed no abnormalities. In view of her known thyroid immunity and history of fatigue, screening of adrenal insufficiency using short synacthen test showed normal baseline, 30- and 60-minute values (239 nmol/L, 717 nmol/L and 850 nmol/L, respectively); unfortunately, paired 17-OH progesterone was not checked at the time. Genetic testing identified a novel heterozygous mutation c.337T>C p.(Tyr113His) in the CYP21A2 gene. This mutation is in a highly conserved region. Bioinformatic analysis suggests that it is highly likely to be pathogenic as a deletion of 8 codons (c332-339), including codon 337, is pathogenic.

CONCLUSION
We report an Emirati female patient with uncommon features of NCAH, including absence of classical hyperandrogenism due to a novel heterozygous variant. Genetic tests amongst relatives and additional molecular and clinical studies are planned to understand the role of this variant in CAH pathology.