Steroid 5alpha-reductase deficiency is a rare autosomal recessive disorder caused by mutations in the SRD5A2-gene, resulting in diminished
dihydrotestosterone (DHT) formation and, hence, in a severe
virilization deficit of the external genitalia in patients with 46,XY karyotype. The phenotype of affected individuals is variable and has been reported to range from completely female over
genital ambiguity to normal male, depending on the type of mutation and its effect on
enzyme activity. Here we report an adolescent 46,XY patient with predominantly female appearance, who had been gonadectomized in early infancy. Genital status revealed a urogenital sinus equivalent to Prader stage III. Molecular genetic analysis demonstrated a homozygous point mutation in exon 2 of the SRD5A2-gene, leading to a premature termination in
codon position 111 of the 5alpha-reductase 2
enzyme, and not allowing formation of a functional 5alpha-reductase type 2
enzyme. This case demonstrates that even despite a complete loss of function of 5alpha-reductase type 2, marked
virilization is possible, most likely the result of a
testosterone (T) effect during foetal life.