5-Alpha Reductase Deficiency - An Uncommon Disorder of Sexual Development: A Case Study of Four Turkish Patients within a Family.

Introduction: 5-alpha reductase deficiency is an inherited autosomal recessive disorder that can present with severe masculinization defects and ambiguous genitalia. Up to more than 100 mutations have been reported, but phenotype and genotype associations have not been directly evidenced. Testosterone-to-dihydrotestosterone (T/DHT) ratio is a clinically diagnostic test, and the cut-off value is expected to be higher than 10.

Case presentation: This brief report of 4 patients with SRD5A2 deficiency in the same family has focused on the clinical and biochemical features of patients with the same mutation. A 14-year-old patient with c193G>C, p. Ala65Pro in SRD5A2 gene had primary amenorrhea and bilateral palpable mass in the inguinal canal. After a detailed physical examination and karyotype analysis, the patient was diagnosed with SRD5A2 deficiency with a 46, XY karyotype. In addition, the other affected siblings had the same clinical phenotype and low masculinization score. T/DHT ratio of all siblings was 14.5, 2.1, 3.7, and 19.2, respectively. Although all of them had the same genetic mutations with a homozygous pattern (c193G>C, p. Ala65Pro), a different T/DHT ratio was observed in our study.

Conclusion: The definitive diagnosis of SRD5A2 deficiency requires molecular testing, but it is currently not available in some centers. Therefore, clinical phenotype and biochemical screening, especially the T/DHT ratio, should be used for evaluating this hereditary syndrome. However, we must consider that the diagnostic sensitivity of the stimulated T/DHT ratio can be affected by various factors, such as age, ethnicity, or the presence of residual enzyme activity.