Background: Mental retardation and other disabilities (including ectopia lentis, osteoporosis, and thromboembolism) in patients who have homocystinuria as a result of a deficiency of cystathionine beta-synthase can be prevented by the screening of newborns with measurement of blood methionine, followed by the early treatment of affected infants. Many infants with this disorder, however, are not identified by screening and have irreversible brain damage.
Methods: We reviewed the results of neonatal screening for homocystinuria over a period of 32 years in New England. Additional specimens were requested for repeated analysis when blood methionine measurements were at or above the established cutoff level. Homocystinuria due to cystathionine beta-synthase deficiency was confirmed by quantitative amino acid analyses.
Results: For the first 23.5 years of the review period, the blood methionine cutoff value was 2 mg per deciliter (134 micromol per liter). Among the 2.2 million infants screened during that period, 8 with homocystinuria were identified (1:275,000). In 1990, the cutoff value was reduced to 1 mg per deciliter (67 micromol per liter). Among the 1.1 million infants screened in the subsequent 8.5 years, 7 with the disorder were identified (1:157,000). During the latter period, the specimens were collected from six of the seven infants when they were two days of age or less; five of the six had blood methionine concentrations below 2 mg per deciliter. Use of the reduced cutoff level increased the false positive rate from 0.006 percent to 0.03 percent.
Conclusions: A cutoff level for blood methionine of 1 mg per deciliter in neonatal screening tests for homocystinuria should identify affected infants who have only slightly elevated concentrations of methionine and reduce the frequency of false negative results.