Dataset Information

Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?

ABSTRACT: Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by PGK-1, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with PGK-1 deficiency and his mother, a carrier of a heterozygous mutation in PGK-1, both of whom presented with early-onset parkinsonism. The boy developed parkinsonism at 9 years of age. His parkinsonism partially responded to levodopa treatment. 123l-metaiodobenzylguanidine (MIBG) uptake was normal. His mother, who exhibited normal PGK-1 activity in erythrocytes, developed parkinsonism at 36 years of age. Her symptoms were undistinguishable from those of Parkinson's disease (PD), despite her normal uptake of MIBG. Neither a point mutation in nor multiplication of SNCA was found. Additionally, hotspots of LRRK2 and GBA were not mutated. To our knowledge, this report provides the first description of parkinsonism in a carrier of PGK-1 deficiency. Interestingly, PGK-1 is located within the confirmed susceptibility locus for PD known as PARK12. These observations suggest that PGK-1 mutations confer susceptibility to PD.

SUBMITTER: Sakaue S

PROVIDER: S-EPMC5459803 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do <i>PGK-1</i> mutations contribute to vulnerability to parkinsonism?

Sakaue Satoshi S Kasai Takashi T Mizuta Ikuko I Suematsu Masaya M Osone Shinya S Azuma Yumiko Y Imamura Toshihiko T Tokuda Takahiko T Kanno Hitoshi H El-Agnaf Omar M A OMA Morimoto Masafumi M Nakagawa Masanori M Hosoi Hajime H Mizuno Toshiki T

NPJ Parkinson's disease 20170331

Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by <i>PGK-1</i>, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with ...[more]

PMID: 28649613

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Dataset Information

Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?

Publications

Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do <i>PGK-1</i> mutations contribute to vulnerability to parkinsonism?

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