A 34-year-old refugee from Somalia was referred because of a suspected DSD. Due to ambiguous, but predominantly female external genitalia at birth he was raised as a girl, whereas his subjective gender identity has always been male. Puberty led to a significant virilization of the body but only to a very limited virilization of the external genitalia. The patient presented himself with an undoubtedly male-type body composition. External genitalia were now predominantly male with micropenis and hypospadia glandis. Small testes could be palpated in both labia between which a small perineal orifice appeared. Sex hormones LH, FSH, testosterone (T), dihydrotestosterone (DHT) DHEAS and androstenedione lay within normal male ranges. Estradiol level was borderline elevated (54 pg/ml, n 27.152.2), whereas Müllerian inhibiting hormone was remarkably increased (35.48 ng/ml, n 1.54.3). Chromosome analysis showed a regular male karyotype. Highly increased T/DHT-ratio of 54 (n 816) in combination with the masculinization defect strictly limited to external genitalia led to the clinical diagnosis of steroid 5 alpha-reductase 2 deficiency (SRD).
SRD is an autosomal recessive, 46, XY DSD leading to an impaired virilization during embryogenesis due to defective conversion of T to DHT. In affected subjects, 5-alpha-reductase activity is reduced in genital skin fibroblasts. Clinical presentation is highly variable from almost entirely female to almost entirely male external genitalia. Pubertal increase in T can be sufficient for virilization of the remainder body at the time of expected puberty as seen in our patient. Consanguinity of patients parents suggests a homozygous mutation in the SRD5A2 gene and a molecular genetic analysis is ongoing in order to identify the mutation. Over 50 different mutations have been described in the past.
Conclusions: This case of a rare DSD elucidates impressively how an enzyme deficiency affects the mechanisms of androgen action in the process of sexual differentiation.