Screening for serum total homocysteine in newborn children

Background: Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B-12 (B-12) deficiency or homocystinuria, but data on the causes of increased tHcy in screening samples are sparse. Methods: Serum concentrations of tHcy, cystathionine, methionine, folate, and B-12 and the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism were determined in 4992 capillary blood samples collected as part of the routine screening program in newborn children. Methylmalonic acid (MMA), gender (SRY genotyping), and the frequency of six cystathionine beta-synthase (CBS) mutations were determined in 20-27% of the samples, including all samples with tHcy >15 mumol/L (n = 127), B-12 <100 pmol/L (n = 159), or methionine >40 mumol/L (n = 154). Results: The median (5th-95th percentile) tHcy concentration was 6.8 (4.2-12.8) mumol/L. B-12 status, as determined by serum concentrations of B-12, tHcy, and MMA, was moderately better in boys than in girls. tHcy concentrations between 10 and 20 mumol/L were often associated with low B-12, whereas tHcy >20 mumol/L (n = 43) was nearly always explained by increased methionine. tHcy did not differ according to folate concentrations or MTHFR 677C>T genotypes. None of the babies had definite CBS deficiencies, but heterozygosity led to low cystathionine, increased methionine, but normal tHcy concentrations. Conclusion: Increased tHcy is a common but not specific finding in newborns. The metabolite and vitamin profiles will point to the cause of hyperhomocysteinemia. Screening for tHcy and related factors should be further evaluated in regions with high prevalence of homocystinuria and in babies at high risk of B,, deficiency. (C) 2004 American Association for Clinical Chemistry.