Homocystinuria and hyperhomocysteinaemia in the Western Cape

Abstract

Research into the role of homocyst(e)ine in cellular functions was stimulated by homocystinuria, a severe autosomal recessive disorder caused by, in the classic case, deficiency of cystathionine β-synthase. Patients with homocystinuria have plasma homocyst(e)ine levels ten times that of reference values. This study was initiated with the presentation and investigation of a local family with clinical symptoms typical of that found in patients with homocystinuria. The free plasma homocystine level detected in the index case was 12 times higher and the plasma methionine level was a 1000 times higher than the respective normal reference ranges. The most common cause of homocystinuria worldwide is a defect in the cystathionine β-synthase enzyme. Methodology was developed to measure cystathionine β-synthase activity in fibroblast cultures obtained from skin biopsies from the extended family. A radioactive method followed by separation of the amino acids on an amino acid analyzer was used. Both the symptomatic siblings had cystathionine β-synthase enzyme activities <1% of the reference value, which was similar to activities found in known homozygotes for cystathionine β-synthase deficiency. Cystathionine β-synthase enzyme activity in the asymptomatic mother was in the lower half of the reference range while the father had cystathionine β-synthase enzyme activity well below the reference range at less than 10% of activity found in healthy individuals. On the basis of clinical symptoms and above parameters, homocystinuria due to cystathionine β-synthase deficiency was onfirmed.