Pyruvate dehydrogenase deficiency disease detected by the enzyme activity of peripheral leukocytes

Background: Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost-effective clinical diagnostic method. Methods: A 4-year-old boy was preliminarily diagnosed with putative Leigh syndrome based on the clinical presentation. PDHC activity in peripheral blood leukocytes and a corresponding gene analysis were subsequently undertaken. Sodium pyruvate 1-C-13 was used for the analysis of PDHC activity in peripheral leukocytes. The genes encoding PDHC were then scanned for mutations. Results: The results showed that the corresponding PDHC activity was dramatically decreased to 10.5 nmol/h/mg protein as compared with that of healthy controls (124.6 +/- 7.1 nmol/h/mg). The ratio of PDHC to citrate synthase was 2.1% (control: 425.3 +/- 27.1). The mutation analysis led to the identification of a missense mutation, NM_000284.4:g214C>T, in exon 3 of PDHC. Conclusion: The peripheral blood leukocyte PDHC activity assay may provide a practical enzymatic diagnostic method for PDHC-related mitochondrial diseases.

Automated summary

This study identified a practical enzymatic diagnostic method for PDHC-related mitochondrial diseases through peripheral blood leukocyte PDHC activity assay and gene mutation analysis. The results showed a dramatically decreased PDHC activity and the identification of a missense mutation in the PDHC gene, providing insights for clinical diagnosis of PDHC deficiency.