Disorders of sex development (DSD) 46.XY due to type 2 5-α reductase deficiency in three siblings: Case report from a low-resource setting

INTRODUCTION AND IMPORTANCE: Disorders of Sexual Development (DSD) is a rare autosomal recessive genetic condition significantly affecting patients' lives in various aspects, particularly psychosocially. Type 2 5-α reductase is a cause of DSD 46,XY. It is rare to find multiple DSDs in the same family. Patients may present with amenorrhea and ambiguous genitalia. This case report is aimed to highlight the genetic aspects of the disease, the challenges to diagnostics and the various management options for the patients. METHODS: Case series of three siblings with DSD 46, XY with relevant discussion. OUTCOMES: Three sisters, aged nineteen, seventeen, and fifteen years old came with an identical complaint of late menarche. Their physical examinations revealed elementary breast development and little axillary hair. The external genitals consisted of vulva, major and minor labia. Clitoromegaly was present with short (<5 cm) vagina. No female internal genital was found but undescended testes were palpable. Presences of testes was confirmed via ultrasound. Laboratory results showed reduced estradiol, highly increased follicle stimulating hormone (FSH), normal male testosterone levels and increased testosterone-dihydrotestosterone ratio (T/DHT >20). Karyotype was 46,XY. Diagnoses of DSD 46, XY due to type 2 5-α reductase deficiency were established. Patient 1 chose female as the gender of choice whilst patients 2 and 3 chose male. All patients are due for corrective surgery along with psychotherapy and psychoeducation. CONCLUSION: DSD 46, XY due to type 2 5-α reductase deficiency is a rare autosomal recessive genetic disorder requiring comprehensive diagnostics and holistic management to improve patient quality of life.