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

Abstract

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 1‐13C 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.

Genotype–phenotype relations for episodic ataxia genes: MDSGene systematic review

“…On review of the latest literature in the EA, published since the closing date of our initial systematic literature review (April 2021–June 2022), we identified a total of nine related articles (Table S4). These reported on 10 patients with novel variants in the CACNA1A [19–29]. In a case report of CACNA1A ‐related EA, dalfampridine 0.3 mg/kg was shown to resolve falls that had been unresponsive to acetazolamide (treatment was delayed due to insufficient literature on the topic) [30].…”

“…Our review of the latest literature (April 2021–June 2022) revealed a total of two related articles (Table S4). These were reported on two patients with novel variants in the PDHA1 gene [19–29].…”

“…These reported on 10 patients with novel variants in the CACNA1A [19][20][21][22][23][24][25][26][27][28][29]. In a case report of CACNA1A-related EA, dalfampridine 0.3 mg/kg was shown to resolve falls that had been unresponsive to acetazolamide (treatment was delayed due to insufficient literature on the topic) [30].…”