A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1 ) causing pyruvate dehydrogenase complex deficiency

JIMD Reports
Jirair K BedoyanGerard T Berry

Abstract

Congenital lactic acidosis due to pyruvate dehydrogenase phosphatase (PDP) deficiency is very rare. PDP regulates pyruvate dehydrogenase complex (PDC) and defective PDP leads to PDC deficiency. We report a case with functional PDC deficiency with low activated (+dichloroacetate) and inactivated (+fluoride) PDC activities in lymphocytes and fibroblasts, normal activity of other mitochondrial enzymes in fibroblasts, and novel biallelic frameshift mutation in the PDP1 gene, c.575dupT (p.L192FfsX5), with absent PDP1 product in fibroblasts. Unexpectedly, the patient also had low branched-chain 2-ketoacid dehydrogenase (BCKDH) activity in fibroblasts with slight elevation of branched-chain amino acids in plasma and ketoacids in urine but with no pathogenic mutations in the enzymes of BCKDH, which could suggest shared regulatory function of PDC and BCKDH in fibroblasts, potentially in other tissues or cell types as well, but this remains to be determined. The clinical presentation of this patient overlaps that of other patients with primary-specific PDC deficiency, with neonatal/infantile and childhood lactic acidosis, normal lactate to pyruvate ratio, elevated plasma alanine, delayed psychomotor development, epileptic encephalopathy,...Continue Reading

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Citations

Apr 14, 2021·Orphanet Journal of Rare Diseases·Eva M M Hoytema van KonijnenburgClara D M van Karnebeek
May 26, 2021·Molecular Reproduction and Development·Li RenBin He

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Methods Mentioned

BETA
acetylation
PCR
electron microscopy

Software Mentioned

Flovent
Pulmicort
Torrent Variant Caller

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