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Newborn screening for 21-hydroxylase deficiency: results of CYP21 molecular genetic analysis
S F Witchel1, S Nayak, M Suda-Hartman
1Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania, USA.
Insights
Newborn screening for congenital adrenal hyperplasia identified mutations in the 21-hydroxylase gene (CYP21) in 80% of infants. Early diagnosis via screening confirmed severe forms of the condition.
Area of Science:
- Pediatric Endocrinology
- Medical Genetics
- Neonatal Screening
Background:
- Congenital adrenal hyperplasia (CAH) is a group of genetic disorders affecting the adrenal glands.
- The 21-hydroxylase gene (CYP21) is commonly implicated in CAH, leading to steroid hormone imbalances.
- Newborn screening programs aim for early detection of critical congenital conditions.
Purpose of the Study:
- To evaluate the utility of newborn screening for identifying infants with mutations in the 21-hydroxylase gene (CYP21).
- To assess plasma steroid hormone levels and genotype in infants identified through screening.
- To determine the prevalence of severe CAH forms in screened neonates.
Main Methods:
- Collected blood samples from 15 infants identified via voluntary newborn screening.
- Performed molecular genotype analysis of the 21-hydroxylase gene (CYP21).
- Measured plasma steroid hormone levels, specifically 17-hydroxyprogesterone.
Main Results:
- Mutations in both CYP21 alleles were found in 12 out of 15 (80%) screened infants.
- All infants with mutations showed significantly elevated plasma 17-hydroxyprogesterone concentrations (> 3500 ng/dl).
- No mutations associated with late-onset CAH were detected; screening identified severe forms.
Conclusions:
- Newborn screening is effective in identifying infants with severe congenital adrenal hyperplasia due to CYP21 mutations.
- Early diagnosis through screening hastened medical intervention for eight infants.
- Screening identified severe 21-hydroxylase deficiency, enabling prompt management.
Abstract:
Blood samples for plasma steroid hormone determinations and molecular genotype analysis of the 21-hydroxylase gene (CYP21) were obtained from 15 infants identified through a voluntary newborn screening program. Mutations were identified on both CYP21 alleles in 12 (80%) of 15 infants; all had confirmatory plasma 17-hydroxyprogesterone concentrations > 3500 ng/dl. No patient was found to carry mutations associated with late-onset 21-hydroxylase deficiency. Newborn screening hastened diagnosis in eight infants.