PMID: 8962591May 1, 1996Paper

Pyruvate dehydrogenase deficiency: the relation of the E1 alpha mutation to the E1 beta subunit deficiency

Pediatric Neurology
T FujiiD C De Vivo

Abstract

We report 7 patients with pyruvate dehydrogenase (PDH) deficiency caused by mutations of the PDH-E1 alpha subunit. Each patient had a different mutation; 4 with duplicate insertions, 1 with a deletion of tandem repeat, and 2 with point mutations. Five of the mutations were novel, thus confirming allelic heterogeneity. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in every patient. Pulse-labeling and chase study for the E1 alpha and E1 beta subunits revealed that initial synthesis of the mutant E1 alpha subunit was normal and posttranslational degradation was complete by 48 hours. However, the post-translational degradation rate of the E1 beta subunit varied from one patient to another. Factors other than instability of the E1 beta monomer must contribute to the degradation rate of this subunit in the presence of an E1 alpha subunit mutation. Including this series, 3 patients with the S312 deletion and 5 with the R302C point mutation have been reported, and all of these patients are female. These findings suggest that these two loci are hot spots for gene mutations, and may be lethal in the male fetus.

References

Dec 1, 1977·The Journal of Clinical Endocrinology and Metabolism·D C DeVivoA S Pagliara
Jan 1, 1992·Journal of Inherited Metabolic Disease·G K Brown
Jan 1, 1989·Annals of the New York Academy of Sciences·G K BrownH H Dahl
Jan 1, 1987·Journal of Inherited Metabolic Disease·G K BrownA C Pollard
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·I D WexlerG Pons
Mar 1, 1970·The Journal of Clinical Investigation·J P BlassB W Uhlendorf
Mar 1, 1993·Journal of Medical Genetics·R M Brown, G K Brown

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Citations

Oct 25, 2001·Archives of Biochemistry and Biophysics·S J JacobiaM S Patel
Nov 20, 2009·Journal of Inherited Metabolic Disease·E QuintanaP Briones
Sep 20, 2011·Current Opinion in Pediatrics·Lea K Parsley, Janet A Thomas

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