title: Females with PDHA1 gene mutations: a diagnostic challenge.
abstract: 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.
authors.affiliation: Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 Nijmegen, HB, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Willemsen
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Alexandra
authors.initials: A
authors.lastname: Teszas
authors.forename: Lambert
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Kosztolanyi
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D017354:Point Mutation; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000175:diagnosis* / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit