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The diagnosis of 5 alpha-reductase deficiency in infancy
Insights
Diagnosis of 5 alpha-reductase deficiency in infancy is reported for the first time in Dominican infants. Elevated urinary tetrahydrocortisol to 5 alpha-tetrahydrocortisol ratios confirmed the condition in male pseudohermaphrodites.
Area of Science:
- Endocrinology
- Genetics
- Biochemistry
Background:
- 5 alpha-reductase deficiency is a rare genetic disorder affecting male sexual development.
- Diagnosis in infancy is crucial for appropriate sex assignment and management.
- Previous diagnostic methods were limited in this age group.
Observation:
- Three male pseudohermaphrodite infants from the Dominican Republic were studied.
- Elevated testosterone to dihydrotestosterone ratios were observed post-hCG stimulation.
- Urinary tetrahydrocortisol (THF) to 5 alpha-tetrahydrocortisol (5 alpha-THF) ratios were analyzed using gas chromatography/mass spectrometry.
Findings:
- Confirmed diagnosis of 5 alpha-reductase deficiency in infancy using elevated THF/5 alpha-THF ratios.
- Infant THF/5 alpha-THF ratios were lower than adult homozygotes but comparable to adult carriers, suggesting higher 5 alpha-reductase activity in infancy.
- Two affected infants were related to a known Dominican kindred and underwent sex of rearing changes after counseling.
Implications:
- Establishes a reliable method for diagnosing 5 alpha-reductase deficiency in infants.
- Highlights the importance of genetic counseling and individualized sex of rearing decisions.
- Provides insights into developmental changes in 5 alpha-reductase activity from infancy to adulthood.
Abstract:
The diagnosis of 5 alpha-reductase deficiency in infancy is reported for the first time in three male pseudohermaphrodites from the Dominican Republic. Basal plasma testosterone to dihydrotestosterone ratios were significantly elevated in two of the three affected infants, and increased markedly in all three infants after administration of hCG. Since urinary etiocholanolone to androsterone ratios could not be determined accurately in this age group, the diagnosis of 5 alpha-reductase deficiency was confirmed by the finding of elevated urinary tetrahydrocortisol (THF) to 5 alpha-tetrahydrocortisol (5 alpha-THF) ratios, as determined by gas chromatography/mass spectrometry, in the affected male infants compared to those in age-matched normal infants. The THF/5 alpha-THF ratios, however, were lower in both the normal children and the affected infants, suggesting increased 5 alpha-reductase activity in infancy. The affected infants had THF/5 alpha-THF ratios comparable to ratios in adult carrier males and significantly lower than ratios in adult homozygotes. Two of the three affected infants are related to the large Dominican kindred we studied previously and initially were raised as females but, after parental counseling, were changed to a male sex of rearing.