title: Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations.
abstract: Fasting and post-methionine load plasma total homocysteine concentrations were investigated in the parents of two homocystinuric patients. Three genetic mutations in the cystathionine beta-synthase gene were found. In the patient of family 1, a frequent Caucasian mutation. T833C, was found on one allele, while the mutation on the other allele has not yet been defined. In the patient of family 2, a mutation C569T, recently described by Sperandeo and colleagues, was found on one allele, while a novel mutation, G346A, was characterized on the other allele. The frequent gene mutation T833C was detected in a heterozygous mother who, surprisingly, exhibited strictly normal fasting and post-methionine load homocysteinaemia. In contrast, in the other family, we found a novel mutation (G346A) in the mother located near Lys 119, the putative binding site of phosphopyridoxal phosphate. This mother exhibited increased fasting and post-methionine load homocysteinaemia. These observations could explain the conflicting results reported for vascular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies.
authors.affiliation: Department of Pediatrics, Federico II University, Naples, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Sperandeo
authors.forename: M
authors.initials: M
authors.lastname: Candito
authors.forename: G
authors.initials: G
authors.lastname: Sebastio
authors.forename: M O
authors.initials: MO
authors.lastname: Rolland
authors.forename: C
authors.initials: C
authors.lastname: Turc-Carel
authors.forename: H
authors.initials: H
authors.lastname: Giudicelli
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
authors.forename: G
authors.initials: G
authors.lastname: Andria
mesh_terms: D000293:Adolescent; D000328:Adult; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation
chemical_list: D006710:Homocysteine; D008715:Methionine; D003541:Cystathionine beta-Synthase