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Pathway Description
Pyruvate Dehydrogenase Complex Deficiency
Homo sapiens
Disease Pathway
Pyruvate dehydrogenase complex deficiency results from a mutation in the E1-alpha polypeptide gene (PDHA1). PDHA1 encodes the pyruvate dehydrogenase complex (PDC) a critical complex that converts pyruvate from glycolysis to acetyl CoA for the citric acid cycle. This conversion step links glycolysis and the citric acid cycle. A defect in this complex causes accumulation of lactate and pyruvate in the blood; lactate and pyruvic acid in the spinal fluid; and lactate in the urine. Symptoms include lactic and metabolic acidosis, motor retardation, dystonia, growth and mental retardation, and respiratory distress.
References
Pyruvate Dehydrogenase Complex Deficiency References
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.120 Heilbronn: SPS Verlagsgesellschaft
Blass JP, Kark AP, Engel WK: Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch Neurol. 1971 Nov;25(5):449-60. doi: 10.1001/archneur.1971.00490050083007.
Pubmed: 5110887
Brown GK, Otero LJ, LeGris M, Brown RM: Pyruvate dehydrogenase deficiency. J Med Genet. 1994 Nov;31(11):875-9. doi: 10.1136/jmg.31.11.875.
Pubmed: 7853374
De Meirleir L, Specola N, Seneca S, Lissens W: Pyruvate dehydrogenase E1 alpha deficiency in a family: different clinical presentation in two siblings. J Inherit Metab Dis. 1998 Jun;21(3):224-6. doi: 10.1023/a:1005347501111.
Pubmed: 9686362
Matthews PM, Brown RM, Otero LJ, Marchington DR, LeGris M, Howes R, Meadows LS, Shevell M, Scriver CR, Brown GK: Pyruvate dehydrogenase deficiency. Clinical presentation and molecular genetic characterization of five new patients. Brain. 1994 Jun;117 ( Pt 3):435-43. doi: 10.1093/brain/117.3.435.
Pubmed: 8032855
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Gray LR, Tompkins SC, Taylor EB: Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci. 2014 Jul;71(14):2577-604. doi: 10.1007/s00018-013-1539-2. Epub 2013 Dec 21.
Pubmed: 24363178
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