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Journal of Inherited Metabolic Disease

, Volume 15, Issue 2, pp 188–197 | Cite as

Persistent hypermethioninaemia with dominant inheritance

  • H. J. Blom
  • A. J. Davidson
  • J. D. Finkelstein
  • A. S. Luder
  • I. Bernardini
  • J. J. Martin
  • A. Tangerman
  • J. M. F. Trijbels
  • S. H. Mudd
  • S. I. Goodman
  • W. A. Gahl
Article

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 byS-adenosylmethionine were also normal, indicating normal regulation ofN5-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.

Keywords

Methionine Homocysteine Cystathionine Methylenetetrahydrofolate Serum Folate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© SSIEM and Kluwer Academic Publishers 1992

Authors and Affiliations

  • H. J. Blom
    • 1
    • 2
  • A. J. Davidson
    • 3
  • J. D. Finkelstein
    • 4
  • A. S. Luder
    • 3
  • I. Bernardini
    • 1
  • J. J. Martin
    • 4
  • A. Tangerman
    • 5
  • J. M. F. Trijbels
    • 2
  • S. H. Mudd
    • 6
  • S. I. Goodman
    • 3
  • W. A. Gahl
    • 1
  1. 1.Section on Human Biochemical Genetics, Human Genetics BranchNational Institute of Child Health and Human DevelopmentBethesdaUSA
  2. 2.Department of PediatricsUniversity Hospital NijmegenNijmegenThe Netherlands
  3. 3.Department of PediatricsUniversity of Colorado Health Sciences CenterDenverUSA
  4. 4.Department of Veteran Affairs Medical CenterWashingtonUSA
  5. 5.Division of Gastrointestinal and Liver Diseases, Department of MedicineUniversity Hospital NijmegenThe Netherlands
  6. 6.National Institute of Mental HealthBethesdaUSA

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