A rare case of 21-hydroxylase deficiency presenting as precocious puberty in a male child

Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that leads to impaired cortisol and/or aldosterone biosynthesis with simultaneous shunting to the intact androgen pathway. In contrast to females, males with CAH due to 21-hydroxylase deficiency may not always be detected at birth, and are often diagnosed later in life subsequent to life threatening adrenal crises and excessive virilization. Case Report: Our case is a 9-year-old boy who presented at the age of 4 years with tall stature, a large penis, pubic hair as well as mild intellectual disability. His biochemical results revealed low follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (1.0 IU/L for both), elevated testosterone 12.5 nmol/L (0.1–0.9), and elevated 17-OH progesterone 87.0 nmol/L (0.5–2.2). Radiological imaging showed physeal closure in consonance with the age of 17 years, normal appearance of the adrenal glands on magnetic resonance imaging (MRI), however, adrenal rests were detected in his testes. The diagnosis was confirmed by biallelic pathogenic variants namely, c.293-13C>G splice site variant and c.955G>A p.(Gln319Ter) in the CYP21A2 gene. Conclusion: The unavailability of universal newborn screening (NBS) in the low-and-middle-income countries contributes to treatable conditions such as CAH being missed particularly in male patients leading to potentially dire consequences to affected patients and their families. Comprehensive clinical assessment, together with appropriate laboratory and radiological investigations are fundamental for timely diagnosis and treatment of non-classical CAH.