The Clinical and Biochemical Spectrum of Human Pyruvate Dehydrogenase Complex Deficiency

Brown, Garry K.; Brown, Ruth; Scholem, R. D.; Kirby, Denise M.; Dahl, Hans Henrik M.

doi:10.1111/j.1749-6632.1989.tb15011.x

Cited by 71 publications

(35 citation statements)

References 21 publications

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“…The observation that the level of leucine did not increase when the concentration of a-KIC in the per fusate was above 2 mM, indicated a limited capability to either take up a-KIC or to transaminate it. This in itself could have additional metabolic consequences since Brown et al [5] and Tildon et al [6] have shown that a-KIC inhibits the transport of pyruvate and lactate, respectively.…”

Section: Discussionmentioning

confidence: 99%

Elevation of Amino Acids in the Interstitial Space of the Rat Brain following Infusion of Large Neutral Amino and Keto Acids by Microdialysis: Alpha-Ketoisocaproate Infusion

et al. 1996

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α-Ketoisocaproate was infused into the brain of free-moving, awake rats by microdialysis to create a microenvironment similar to that found in maple syrup urine disease. The eluate of the probe was analyzed for amino acids to detennine if α -ketoisocaproate was transaminated to leucine and if the amino acid homeostasis was altered. The interstitial levels of leucine were increased up to 11-fold and other large neutral amino acids were increased 2-to 3-fold indicating an active branched chain keto acid transaminase activity and enhanced hetero-exchange across cell membranes. The elevation of large neutral amino acids in the interstitial space is discussed in terms of the synthesis of leucine and neurotransmitters in maple syrup urine disease.

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Section: Discussionmentioning

confidence: 99%

Elevation of Amino Acids in the Interstitial Space of the Rat Brain following Infusion of Large Neutral Amino and Keto Acids by Microdialysis: Alpha-Ketoisocaproate Infusion

et al. 1996

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“…Four main neurological presentations have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome and relapsing ataxia (Robinson et al 1987;Brown et al 1988Brown et al , 1989aBarnerias et al 2010;Patel et al 2012). The majority of patients have a mutation located in the PDHA1 gene encoding the E1a subunit, which is located on the X chromosome (Robinson and Sherwood 1984;McKay et al 1986;Wicking et al 1986;Brown et al 1989b;Lissens et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment

Dongen

Brown

et al. 2014

JIMD Reports

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“…They found that the residual PDH E1 activity correlated with the percentage of the mutated X-chromosome that escaped inactivation. Brown et al (1989b) made the observation that developmental defects of the brain are only seen in girls, whereas little cerebral pathology is found in boys with severe neonatal presentation, possibly because severe PDH deficiency of the brain leads to fetal death in boys.…”

Section: Discussionmentioning

confidence: 98%

“…The clinical severity is dependent on residual enzyme activity. Tissue-specific association is determined by the possibility of different tissues being able to use alternate energy sources (Brown et al 1989b). In males, the deficiency will be present in all cells, whereas females are necessarily mosaics.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the Elα subunit

et al. 1992

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We report the molecular characterization of a case of a functional PDH-E1 (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-E1 activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-E1 alpha mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal E1 alpha cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis.

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The Clinical and Biochemical Spectrum of Human Pyruvate Dehydrogenase Complex Deficiency

Cited by 71 publications

References 21 publications

Elevation of Amino Acids in the Interstitial Space of the Rat Brain following Infusion of Large Neutral Amino and Keto Acids by Microdialysis: Alpha-Ketoisocaproate Infusion

Elevation of Amino Acids in the Interstitial Space of the Rat Brain following Infusion of Large Neutral Amino and Keto Acids by Microdialysis: Alpha-Ketoisocaproate Infusion

Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment

Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the Elα subunit

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