Neuropediatrics 2004; 35 - P88
DOI: 10.1055/s-2004-819460

Hyperhomocysteinemia as a marker of methylentetrahydrofolate reductase deficiency in two siblings with early neurodegeneration

B Plecko 1, K Kaltenbrunner 2, W Erwa 3, J Simbrunner 4, HG Koch 5, B Fowler 6
  • 1Department of Pediatrics, University Hospital Graz, Austria
  • 2Children's Hospital Villach, Austria
  • 3Institute for Medical and Chemical Laboratory Diagnosis, Graz, Austria
  • 4 Department of Radiology, University Hospital Graz, Austria
  • 5 Department of Pediatrics, University Hospital Muenster, Germany
  • 6Department of Pediatrics, University Hospital Basel, Switzerland

Introduction: Beside so called screening tests, many inborn errors have to be detected by measurement of a single metabolite or enzyme assay.

Case report: We report on two siblings, who both presented muscular hypotonia, loss of vision, apnea and acquired microcephaly in infancy. Both died due to progressive brain atrophy at the age of 29 and 14 months respectively. Extended neurometabolic investigations did not reveal any abnormal results until isolated, marked elevation of homocystein (110 and 137µmol/l normal<14) was detected in plasma of both patients. In the presence of normal blood count and organic acids this raised the suspicion of methylentetrahydrofolate reductase (MTHFR) deficiency, which was confirmed by low enzyme activity (3,5% of normal) in cultured fibroblasts. Molecular analysis of the MTHFR gen revealed a homozygous stop mutation in exon 11.

Conclusion: Inborn errors, due to their rarity and variable phenotypes may pose considerable diagnostic problems. As homocystein is a marker for a big group of inborn errors involved in remethylation, most of them treatable, we would advocate to include the determination of plasmahomocystein in the metabolic screening of children with unclear retardation and neurodegeneration.

Key words: brain atrophy, homocystein, folate metabolism, remethylation