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A cognitively normal PDH‐deficient 18‐year‐old man carrying the R263G mutation in the PDHA1 gene
Author(s) -
BachmannGagescu R.,
Merritt J. Lawrence,
Hahn S. H.
Publication year - 2009
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-1101-4
Subject(s) - pyruvate dehydrogenase complex , ataxia , lactic acidosis , endocrinology , medicine , thiamine , citric acid cycle , mitochondrial disease , biology , ketogenic diet , mutation , pyruvate decarboxylation , genetics , epilepsy , gene , biochemistry , enzyme , metabolism , psychiatry , mitochondrial dna
Summary Pyruvate dehydrogenase (PDH) is a crucial multienzyme system linking glycolysis to the tricarboxylic acid cycle by catalysing the decarboxylation of pyruvate to acetyl‐CoA. Deficiency in pyruvate dehydrogenase is most commonly secondary to mutations in the X‐linked PDHA1 gene encoding the E1 alpha subunit. There is a wide range of clinical presentations from severe neonatal lactic acidosis to chronic encephalopathy (Leigh syndrome). In recent years, a small subset of patients was recognized with less severe involvement, presenting initially only with intermittent symptoms, mainly of ataxia. Most of these patients remain stable for a number of years before developing progressive neurological deterioration around puberty at the latest. There does not appear to be a reliable correlation between genotype, phenotype, or enzyme activity. This makes counselling in a clinical setting challenging. We report a case with a previously known common mutation in PDHA1 (R263G) with an excellent outcome at 18 years of age. Previous patients with this mutation have presented with mental retardation and/or Leigh syndrome, while our patient's clinical outcome is exceptional. He is cognitively normal and has normal brain MRI. His management includes a stringent carbohydrate‐free diet, as well as supplementation with thiamine, carnitine and vitamin E. This case further broadens the clinical spectrum, including now an example of a cognitively normal adult with PDH deficiency.