Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1alpha subunit

American Journal of Medical Genetics. Part a
Jessie M CameronB H Robinson

Abstract

Pyruvate dehydrogenase (PDH)-complex deficiency (OMIM 312170) is a clinically heterogeneous disorder, with phenotypes ranging from fatal lactic acidosis (LA) in the newborn to chronic neurological dysfunction. To date, over 80 different mutations have been identified in the PDHA1 gene in patients with PDH complex deficiency, which are thus thought to contribute to the PDH deficient phenotype. We have identified 14 additional patients with total PDH complex deficiency, all of whom were found to contain mutations within the PDHA1 gene (E(1)alpha subunit). The mutations include both missense mutations and duplications. Eight of these patients had novel mutations, and the remaining had mutations that have been identified previously in PDH complex deficient patients, with residual fibroblast activity ranging from 2.4 to 69% of control values. The nature of these mutations illustrates the variability in phenotype for a given gene defect, with intermittent ataxia being the mildest presentation, Leigh syndrome being the most common and severe neonatal LA the most severe.

References

May 1, 1981·The Journal of Clinical Investigation·K F SheuM F Utter
Dec 1, 1996·Biochemical and Molecular Medicine·S PitkänenB H Robinson

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Citations

Jul 30, 2009·Journal of Inherited Metabolic Disease·R Bachmann-GagescuS H Hahn
Jun 12, 2009·Journal of Inherited Metabolic Disease·E OstergaardF Wibrand
Sep 4, 2010·Journal of Developmental and Behavioral Pediatrics : JDBP·Marni J Falk
Mar 23, 2006·European Journal of Pediatrics·Francois-G DebrayGrant A Mitchell
Apr 1, 2009·Biochemical and Biophysical Research Communications·Teresa RizzaRosalba Carrozzo
Oct 21, 2010·Pediatrics International : Official Journal of the Japan Pediatric Society·Satoshi SatoAkinori Hoshika
Jun 7, 2017·Human Genome Variation·Takanobu YoshidaKimitoshi Nakamura
Nov 6, 2018·Current Genetic Medicine Reports·Elizabeth M McCormickMarni J Falk
Feb 5, 2008·Molecular Genetics and Metabolism·UNKNOWN Mitochondrial Medicine Society's Committee on DiagnosisRobert K Naviaux
Apr 4, 2009·Analytical Biochemistry·Matthew J RardinJack E Dixon
Oct 1, 2021·Mitochondrion·Narayanappa GayathriShivani Sharma

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