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Persistent hypermethioninaemia with dominant inheritance
Author(s) -
Blom H. J.,
Davidson A. J.,
Finkelstein J. D.,
Luder A. S.,
Bernardini I.,
Martin J. J.,
Tangerman A.,
Trijbels J. M. F.,
Mudd S. H.,
Goodman S. I.,
Gahl W. A.
Publication year - 1992
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799629
Subject(s) - cystathionine beta synthase , methionine adenosyltransferase , methionine , homocystinuria , homocysteine , methionine synthase , medicine , transmethylation , cystine , endocrinology , biology , catabolism , methylenetetrahydrofolate reductase , transsulfuration , biochemistry , transamination , enzyme , amino acid , metabolism , gene , allele , cysteine
Summary A clinically benign form of persistent hypermethioninaemia with probable dominant inheritance was demonstrated in three generations of one family. Plasma methionine concentrations were between 87 and 475 µmol/L (normal mean 26 µmol/L; range 10–40 µmol/L); urinary methionine and homocystine concentrations were normal. Plasma homocystine, cystathionine, cystine and tyrosine were virtually normal. The concentrations in serum and urine of metabolites formed by the methionine transamination pathway were normal or moderately elevated. Methionine loading of two affected family members revealed a diminished ability to catabolize methionine, but the activities of methionine adenosyltransferase and cystathionine β‐synthase were not decreased in fibroblasts from four affected family members. Fibroblast methylenetetrahydrofolate reductase activity and its inhibition by S ‐adenosylmethionine were also normal, indicating normal regulation of N 5 ‐methyltetrahydrofolate‐dependent homocysteine remethylation. Serum folate concentrations were not increased. The findings in this family differ from those previously described for known defects of methionine degradation. Since the hepatic and fibroblast isoenzymes of methionine adenosyltransferase differ in their genetic control, this family's biochemical findings appear consistent with a mutation in the structural gene for the hepatic methionine adenosyltransferase isoenzyme.