{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:32:02Z","timestamp":1775025122672,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[1996,7,1]],"date-time":"1996-07-01T00:00:00Z","timestamp":836179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1996,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E<jats:sub>1<\/jats:sub> component, specifically due to mutations in the X\u2010linked E<jats:sub>1<\/jats:sub><jats:italic>\u03b1<\/jats:italic> gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate\u2010sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X\u2010inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3\u2032 end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin\u2010responsiveness of the enzyme and the patient's clinical symptoms.<\/jats:p><jats:p>Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian\u2010speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross\u2010reactive to pyruvate carboxylase antibody is present in cultured cells (CRM<jats:sup>+ve<\/jats:sup>). In the latter group, cross\u2010reacting material is rarely present (CRM<jats:sup>\u2212ve<\/jats:sup>). The CRM<jats:sup>+ve<\/jats:sup> patients can survive into teenage years with careful supervision, while the CRM<jats:sup>\u2212ve<\/jats:sup> patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.<\/jats:p>","DOI":"10.1007\/bf01799106","type":"journal-article","created":{"date-parts":[[2005,6,27]],"date-time":"2005-06-27T21:01:28Z","timestamp":1119906088000},"page":"452-462","source":"Crossref","is-referenced-by-count":57,"title":["Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex"],"prefix":"10.1002","volume":"19","author":[{"given":"B. 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Children  555 University Avenue Toronto Ontario M5G 1X8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Ling","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Paediatrics University of Toronto  Toronto Ontario M5G 1X8 Canada"},{"name":"Department of Genetics, The Research Institute The Hospital for Sick Children  555 University Avenue Toronto Ontario M5G 1X8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1996,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00711616"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(89)90297-8"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90543-4"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.4.449"},{"key":"e_1_2_1_6_1","first-page":"558","article-title":"Mutations in the X\u2010linked E1\n 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