Spectrum of hypermethioninemia in neonatal screening

Measurement of methionine levels in dried blood spots has been one of the items of neonatal screening in Taiwan for more than 20 years. In 1,701,591 newborns, 17 cases of hypermethioninemia were detected, but among them only one had homocystinuria. More than half of the 16 cases of isolated hypermethioninemia had mutations in the MAT1A gene, and four of the eight MAT1A mutations identified in this study have not been reported before. Therefore methionine adenosyltransferase deficiency is the most prevalent cause of isolated hypermethioninemia in Taiwanese. Although most of the patients with isolated hypermethioninemia were put on diet in this study, their IQ scores were not related to either the initial or follow-up plasma methionine levels. Because both the etiology and the natural history of isolated hypermethioninemia haven't been clearly resolved, the impact of this condition on screening programs where homocystinuria is rare should be carefully evaluated.