Females with
salt-wasting (SW)
21-hydroxylase deficiency (21OHD) may present with mild external genitalia
virilization, despite complete or almost complete
enzyme inactivation. We therefore analyzed genotype/phenotype correlation in 13 Japanese female patients with SW 21OHD. Criteria for classification into the SW phenotype included history of a
salt-losing crisis with documented
hyponatremia,
hyperkalemia, and markedly elevated plasma
renin activity. Urologists and pediatricians determined the Prader genital stage and classified the location of the vaginal entrance into the common urogenital sinus as low, moderate, or high. CYP21A2 gene, coding for
21-hydroxylase, was analyzed with Southern blotting and direct sequencing. Genotypes were categorized into four mutation groups, based on the degree of enzymatic activity (N, complete
enzyme inactivation; groups A, < 2%,
B, 3-7%, and C > 30%). Basal
androgen levels were available from only six out of thirteen patients, so we could not relate
androgen levels with the severity of external genitalia
virilization. We compared the degree of external genitalia
virilization with genotype. The severity of external genitalia
virilization varied from Prader stage 1 to 4. One patient who presented with Prader 1 had a genotype consistent with Group B. In addition, discordance between Prader classification and the location of the vaginal entrance was noted; one patient classified as Prader 4 showed low vaginal entrance, while another patient classified as Prader 3 showed high vaginal entrance. The degree of the impairment of
21-hydroxylase activity does not correlate with the severity of
virilization of the external genitalia in female patients with the SW type of 21OHD.