Human Genetics

, Volume 89, Issue 3, pp 259–264

Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase

  • Ana Maria Crane
  • Laura S. Martin
  • David Valle
  • Fred D. Ledley
Original Investigations

DOI: 10.1007/BF00220536

Cite this article as:
Crane, A.M., Martin, L.S., Valle, D. et al. Hum Genet (1992) 89: 259. doi:10.1007/BF00220536

Summary

We have previously identified a mutation in the gene for methylmalonyl CoA mutase in a patient with the mut- phenotype of methylmalonic aciduria. This mutation (G717V) interferes with the binding of the deoxyadenosylcobalamin cofactor to the apoenzyme producing a mutant holoenzyme that is defective, but not completely inactive, in vitro. This report describes the clinical phenotype associated with this mutation in the original patient and two additional patients who are homozygous for this allele. All three patients presented in the first years of life with multiple episodes of life-threatening organic acidosis and hyperammonemia. None had evidence of disease in the perinatal period, and all three have low-normal intelligence. These three children exhibit a distinctive phenotype of disease that is intermediate between the fulminant and benign forms of methylmalonic aciduria. These data suggest that this phenotype is the specific consequence of the G717V mutation, and that the degree of residual enzyme activity associated with the G717V mutation is close to the threshold required in vivo for maintaining metabolic homeostasis.

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Ana Maria Crane
    • 1
  • Laura S. Martin
    • 2
  • David Valle
    • 2
  • Fred D. Ledley
    • 1
  1. 1.Departments of Cell Biology and PediatricsHoward Hughes Medical Institute, Baylor College of MedicineHoustonUSA
  2. 2.Center for Medical Genetics, Howard Hughes Medical InstituteJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Cell BiologyBaylor College of MedicineHoustonUSA