Methionine loading in a Down's syndrome patient with cerebral infarction.

Abstract

In homozygotes, inherited defects in cystathionine p-synthase (CBS; EC 4.2.1.22) activity result in severe hyperhomocysteinaemia, with early onset of arteriosclerosis as well as lifethreatening thrombo-embolism among its most prominent symptoms. I Mild hyperhomocysteinaemia, comparable to that occurring in heterozygotes for CBS deficiency, has also been reported to predispose to premature vascular diseases, including embolic strokes.i-' Homozygosity for a thermolabile variant of 5,10methylenetetrahydrofolate reductase (MTHFR; EC 1.1.1.68), which may cause mild or moderate hyperhomocysteinaemia especially in cases with low folate intake, has also been suggested to be a genetic risk factor in vascular disease. The methionine loading test, with determination of total plasma homocysteine in the fasting state as well as 6 h after oral administration of 0·1 g methionine/kg body weight under standardized conditions, represents a well-established tool for the detection of patients carrying an increased risk of occlusive vascular disease associated with mild or moderate hyperhomocysteinaemia.t-' The CBS gene has been assigned to chromosome 21, the triple chromosome in Down's syndrome (Trisomy 21). In vitro data have indicated a 1'66-fold increased CBS activity in the fibroblasts of Down's syndrome patients.P This observation was explained with the gene dosage effect and also used to explain the reduced tendency of such patients to arteriosclerosis. However, CBS gene disruption on two of the three chromosomes 21 should still result in much decreased CBS activity. Here, we present the first report on the methionine loading test performed in a patient with Down's syndrome after a cerebral infarction, which was