Females with PDHA1 gene mutations: A diagnostic challenge

Marjolein Willemsen, Richard J.T. Rodenburg, Alexandra Teszas, Lambert van den Heuvel, Gyorgy Kosztolanyi, Eva Morava

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Biochemical analysis was performed in muscle tissue and in fibroblasts of four unrelated females consecutively diagnosed with a 'de novo' point mutation in the PDHA1 gene. Pyruvate dehydrogenase E1 subunit deficiency was confirmed in the muscle sample of all patients, however, in three out of four cases the activity of the pyruvate dehydrogenase complex in fibroblasts showed a normal activity. A skewed inactivation was confirmed of the maternal X chromosome in fibroblasts in all children. Due to the possibility of a skewed X inactivation pattern enzyme measurements in fibroblasts are not always reliable for the diagnosis of a PDHc defect in females. Based on the overlapping features of PDHc deficiency with those of the disorders of the oxidative phosphorylation we suggest performing a fresh muscle biopsy for detailed biochemical analysis in females with a suspected pyruvate dehydrogenase deficiency, followed by molecular genetic analysis of the PDHA1 gene.

Original languageEnglish (US)
Pages (from-to)155-159
Number of pages5
Issue number3
StatePublished - Jun 2006


  • Females
  • Fibroblast
  • Mitochondrial disease score
  • Muscle biopsy
  • PDH
  • Skewed X inactivation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology


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