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Screening for serum total homocysteine in newborn children
Helga Refsum1, Anne W Grindflek, Per M Ueland
1Department of Pharmacology, University of Oxford, UK. helga.refsum@pharmacology.oxford.ac.uk
Insights
Newborn screening for high total homocysteine (tHcy) is common but not specific. Metabolite and vitamin profiles help identify causes like vitamin B12 deficiency or homocystinuria.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Newborn screening for total homocysteine (tHcy) aids in detecting vitamin B12 deficiency and homocystinuria.
- Limited data exists on the specific causes of elevated tHcy in newborn screening samples.
Purpose of the Study:
- To investigate the causes of elevated total homocysteine (tHcy) in newborn screening samples.
- To correlate tHcy levels with vitamin B12, methionine, folate, and specific genetic factors.
Main Methods:
- Analyzed serum concentrations of tHcy, cystathionine, methionine, folate, and vitamin B12 in 4992 newborn samples.
- Assessed MTHFR 677C > T polymorphism, MMA, gender, and CBS mutations in a subset of samples, including those with abnormal tHcy, B12, or methionine levels.
Main Results:
- Median tHcy was 6.8 micromol/L; boys had slightly better B12 status than girls.
- Elevated tHcy (10-20 micromol/L) often linked to low vitamin B12; tHcy > 20 micromol/L typically indicated increased methionine.
- No definite CBS deficiencies found, but CBS heterozygosity affected cystathionine and methionine levels without altering tHcy.
Conclusions:
- Elevated tHcy in newborns is frequent but non-specific.
- Metabolite and vitamin profiles are crucial for diagnosing hyperhomocysteinemia causes.
- Further evaluation of tHcy screening is recommended in high-risk populations for homocystinuria and vitamin B12 deficiency.
Background:
Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B12 (B12) 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 B12 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 micromol/L (n = 127), B12 < 100 pmol/L (n = 159), or methionine > 40 micromol/L (n = 154).
Results:
The median (5th-95th percentile) tHcy concentration was 6.8 (4.2-12.8) micromol/L. B12 status, as determined by serum concentrations of B12, tHcy, and MMA, was moderately better in boys than in girls. tHcy concentrations between 10 and 20 micromol/L were often associated with low B12, whereas tHcy > 20 micromol/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 B12 deficiency.
