Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?
| Autor: | Takahiko Tokuda, Omar M. A. El-Agnaf, Satoshi Sakaue, Takashi Kasai, Yumiko Azuma, Ikuko Mizuta, Masaya Suematsu, Hitoshi Kanno, Shinya Osone, Masafumi Morimoto, Toshiki Mizuno, Masanori Nakagawa, Hajime Hosoi, Toshihiko Imamura |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Parkinson's disease Early onset parkinsonism Biology medicine.disease_cause 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine medicine Heterozygous carrier RC346-429 Myopathy Phosphoglycerate kinase 1 education Genetics Mutation education.field_of_study Phosphoglycerate Kinase Deficiency business.industry Parkinsonism Point mutation medicine.disease LRRK2 030104 developmental biology Endocrinology Neurology Neurology. Diseases of the nervous system Neurology (clinical) medicine.symptom business Asymptomatic carrier 030217 neurology & neurosurgery |
| Zdroj: | npj Parkinson's Disease, Vol 3, Iss 1, Pp 1-3 (2017) |
| ISSN: | 2373-8057 |
| DOI: | 10.1038/s41531-017-0014-4 |
| Popis: | 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. Mutations in the gene encoding phosphoglycerate kinase 1 (PGK-1) may confer susceptibility to early-onset Parkinson’s disease (PD). PGK-1 is a crucial protein for the breakdown of sugar in the body and mutations that cause PGK-1 deficiency lead to an X-linked metabolic disorder characterised by the breakdown of red blood cells, muscle weakness and various central nervous system abnormalities. Takashi Kasai at Kyoto Prefectural University of Medicine, Japan, and colleagues describe early-onset PD symptoms in a 9 year old boy with PGK-1 deficiency and his mother at 36 years of age. This is the first report of parkinsonism developing in an otherwise asymptomatic carrier of a PGK-1 mutation. The location of the PGK-1 gene on the X chromosome is within a confirmed susceptibility region for PD known as PARK12, suggesting that PGK-1 may directly contribute to the disease. |
| Databáze: | OpenAIRE |
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