Molecular diagnosis resulted in favoring male sex assignment in affected newborns.Many SRD5A2 mutations come from areas with high coefficients of inbreeding, including the Dominican Republic (where people with the condition are called güevedoces – "testes at twelve"), and Papua New Guinea (where it is known as kwolu-aatmwol – suggesting a persons transformation "into a male thing"), and Turkey.In the Dominican Republic, güevedoces are regarded as a third gender and experience ambivalent gender socialisation. In adulthood, they most commonly self-identify as men, but are not necessarily completely treated as such by society. In the cases in Papua New Guinea, it has been said that the "girl" is shunned when he begins his natural transformation into a male body and socially assumes a male gender role. History
An autosomal recessive disorder of sex development, described as pseudovaginal perineoscrotal hypospadias (PPSH), was discovered in males in 1961. The main feature of this syndrome was female appearing external genitalia with the presence of bilateral testes and male urogenital tracts in which the ejaculatory ducts terminate in a blind-ending vagina. This disorder was consistent with 5αR2D as the underlying cause as observed in animal models. 5αR2D was confirmed as the cause in humans in 1974, when studies of 24 participants in the Dominican Republic and 2 in Dallas Texas, USA. One of the cases in Dallas began to virilze at puberty and underwent surgery to remove testes and "repair" the apparent clitoromegaly. During surgery, a normal male urogenital tract was observed as well as other features consistent with PPSH.
With the determination of an XY karyotype and normal SRY, the differential diagnosis of 46,XY DSD is made with endocrinological measurements of T/DHT ratios (which indicate 5αR2 activity) and precise anatomical imaging since 5αR2D can be difficult to distinguish from other causes of 46,XY DSD (e.g., partial androgen insensitivity syndrome and 17β- hydroxysteroid dehydrogenase type 3 enzyme deficiencies).The measurement of the serum DHT concentration is challenging since the concentrations are low and DHT has a high level of cross-reactivity. A high level of assay specificity is required to measure concentrations of DHT since serum T levels are generally 10 fold higher than DHT in young males. Endocrinological tests for T/DHT ratios can be difficult to interpret since the normal ratio level varies according to age and severity of 5αR2 activity impairment. Affected young males of at least pubertal age with normal serum T levels demonstrate elevated T/DHT levels (normal T, lower than normal DHT). Stimulation with human chorionic gonadotropin (hCG) (alternatively, testosterone enanthate) is required in prepubertal children (with stimulation and samples taken over several days) to increase serum testosterone levels for measurement. Interpreting T/DHT ratios in male newborns is especially challenging due to neonatal testosterone surge and higher than normal 5a-reductase type 1 activity. SRD5A2 gene analysis is recommended for diagnosis in newborns. Broadly, 5αR2D is diagnosed with T/DHT ratios greater than 18 while ratios greater than 30 have been observed in severely affected individuals.