ESPE Abstracts

Background: Deficiency of 21-hydroxylase (CYP21A2) is responsible of 90-95% of all cases of congenital adrenal hyperplasia (CAH). CYP21A2 converts 17OHprogesterone into 11deoxycortisol and is encoded by the CYP21A2 gene on chromosome 6p21.3, within the class III region of the highly polymorphic HLA histocompatibility complex. CAH refers to a group of autosomal recessive disorders. Nonclassic CAH (NCAH) is milder and more common, however it may not be identified until childhood or early adulthood. Clinical features in late childhood include premature adrenarche, acne and accelerated bone age. Adolescent and adult females present with acne, hirsutism and menstrual irregularity. The frequency of NCAH is ethnic-specific, with the prevalence being even higher among Mediterraneans, Hispanics, and Eastern European Jews (1/1000-1/100).

Objective: We report an 7-year-old girl with precocious adrenarche, who was investigated for CAH.

Case Presentation: An 7-year-old girl was admitted as the first clinical feature of CAH, for evaluation of pubic hair. Clinical examination showed precocious adrenarche, Tanner stage pubic hair III, without any secondary sex characteristics maturation. The past medical history includes multiple respiratory infections. All tests for early puberty were negative (synacthen test, bone age, hormonal investigations) except for the U/S, which revealed adrenal hyreplasia. Genetic analysis was performed using whole-exome sequencing.

Results: Molecular genetic testing confirmed compound heterozygous mutations in the CYP21A2 gene: p.P453S (c.1357C>T) (maternal mutation) and p.P30L (c.89C>T) (paternal mutation) at exons 10 and 1 respectively. Diagnosis of compound heterozygote of NCAH was established and hydrocortisone therapy was initiated.

Conclusion: Approximately two-thirds of patients with NCAH are compound heterozygotes. Hundreds of mutations of CYP21A2 have been described, with p.P453S, p.P30L among 12 most common for the nonclassic phenotype. As NCAH presents with a wide range of clinical variants the patient phenotype cannot be predicted based on the mutations of the CYP21A2 gene, as NCAH can present with a wide range of clinical variants.