Early diagnosis and management of 5 a - reductase deficiency

Two siblings of Pakistani origin, karyotype 46 XY, were born with predominantly female external genitalia with minute phallus, bifid scrotum, urogenital sinus, and palpable gonads. The older sibling at the age of 8 days showed an adequate testosterone response to human chorionic gonadotrophin (hCG) stimulation. The diagnosis of Sa-reductase deficiency was made at age 6 years when no 5areduced glucocorticoid metabolites were detectable in urine even after tetracosactrin (Synacthen) stimulation. In the younger sibling the diagnosis of Sa-reductase deficiency was provisionally made at the early age of 3 days on the basis of high urinary tetrahydrocortisol (THF)/allotetrahydrocortisol (5 a-THF) ratio and this ratio increased with age confirming the diagnosis. Plasma testosterone: dihydrotestosterone (DHT) ratio before and after hCG stimulation was within normal limits at age 3 days but was raised at age 9 months. Topical DHT cream application to the external genitalia promoted significant phallic growth in both siblings and in the older sibling corrective surgery was facilitated. In prepubertal male pseudohermaphrodites with normal or raised testosterone concentrations, phallic growth in response to DHT cream treatment could be an indirect confirmation of 5a-reductase deficiency. Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow G3 8SJ I Odame M D C Donaldson W Cochran P J Smith Institute of Biochemistry, Royal Infirmary, Glasgow A M Wallace Correspondence to: Dr Donaldson. Accepted 31 January 1992 Deficiency of Sa-reductase was described as a distinct biochemical entity in 1974.' 2 The condition is inherited as an autosomal recessive disorder and is characterised by external female phenotype at birth, presence of bilateral testes and normally developed internal male genitalia, including seminal vesicles and ejaculatory duct, while at puberty there is variable virilisation of the external genitalia accompanied by the development of pubic and axillary hair. ' The biochemical abnormalities characteristic of 5a-reductase deficiency are clearly described in adults and older children but it is only recently that the diagnosis has been made in infancy, the critical period for sex determination in the newborn with ambiguous genitalia.3 5-7 The typical pattern is that of normal or raised concentration of plasma testosterone with decreased dihydrotestosterone (DHT) and increased testosterone: DHT ratio especially after human chorionic gonadotrophin (hCG) stimulation.5 6 8 Additional abnormalities include reduced levels of Sa-reduced urinary glucocorticoid and androgen metabolites, for example, allotetrahydrocortisol (5a-THF) and androsterone.9 ' In infancy measurement of these steroid metabolites can be difficult as they are present at low concentrations in the presence of high concentrations of steroid metabolites of similar structure. Sensitive detection methods of high specificity (for example, gas chromatography/mass spectrometry) are therefore required.7 Decreased 5a-reductase activity in fibroblasts cultured from genital skin may also aid diagnosis." 12 We describe two siblings with Sa-reductase deficiency, the younger of whom was diagnosed shortly after birth. In both siblings DHT treatment was of value in increasing phallic size.