HOMOCYSTEINE RESPONSE TO METHIONINE CHALLENGE IN 4 OBLIGATE HETEROZYGOTES FOR HOMOCYSTINURIA AND RELATIONSHIP WITH CYSTATHIONINE BETA-SYNTHASE MUTATIONS

Fasting and post-methionine load plasma total homocysteine concentrati ons were investigated in the parents of two homocystinuric patients. T hree genetic mutations in the cystathionine beta-synthase gene were fo und. In the patient of family 1, a frequent Caucasian mutation, T833C, was found on one allele, while the mutation on the other allele has n ot yet been defined. In the patient of family 2, a mutation C569T, rec ently described by Sperandeo and colleagues, was found on one allele, while a novel mutation, G(346)A, was characterized on the other allele . The frequent gene mutation T833C was detected in a heterozygous moth er who, surprisingly, exhibited strictly normal fasting and post-methi onine load homocysteinaemia. In contrast, in the other family, we foun d a novel mutation (G(346)A) in the mother located near Lys 119, the p utative binding site of phosphopyridoxal phosphate. This-mother, exhib ited increased fasting and post-methionine load homocysteinaemia. Thes e observations could explain the conflicting results reported for vasc ular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies.