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The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency.

Abstract
Eight cases of isolated human pyruvate carboxylase deficiency were examined from seven families. Although all patients presented with a chronic lacticacidemia, two particular patients presented with the added features of hyperammonemia, citrullinemia, and hyperlysinemia. When cultured skin fibroblasts from these patients were examined for their ability to synthesize [3H]biotin-containing proteins, it was found that the two patients who presented with hyperammonemia, citrullinemia, and hyperlysinemia did not synthesise a protein of the correct subunit molecular weight (Mr = 125 K daltons) corresponding to pyruvate carboxylase. In addition, when skin fibroblast proteins were labeled with [35S]methionine, cross-reacting material (CRM) corresponding to pyruvate carboxylase was immunoprecipitated by antipyruvate carboxylase antiserum in most patients, but again the two patients with the atypical presentation showed no CRM. We propose that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruvate carboxylase gene, one that results in the synthesis of a relatively inactive pyruvate carboxylase protein CRM(+ve) and one that results in the lack of expression of the gene in the form of a recognizable protein CRM(-ve).
AuthorsB H Robinson, J Oei, W G Sherwood, D Applegarth, L Wong, J Haworth, P Goodyer, R Casey, L A Zaleski
JournalAmerican journal of human genetics (Am J Hum Genet) Vol. 36 Issue 2 Pg. 283-94 (Mar 1984) ISSN: 0002-9297 [Print] United States
PMID6424438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Pyruvate Dehydrogenase Complex
  • Biotin
  • Pyruvate Carboxylase
Topics
  • Biotin (metabolism)
  • Cells, Cultured
  • Chemical Precipitation
  • Cross Reactions
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Fibroblasts (enzymology)
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Weight
  • Mutation
  • Pyruvate Carboxylase (biosynthesis, genetics)
  • Pyruvate Carboxylase Deficiency Disease
  • Pyruvate Dehydrogenase Complex (metabolism)
  • Skin (cytology)
  • Syndrome

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