Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction

Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 defi...

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Bibliographic Details
Published in:Parkinsonism & related disorders Vol. 64; pp. 319 - 323
Main Authors: Morales-Briceño, Hugo, Ha, Ainhi D., London, Kevin, Farlow, David, Chang, Florence C.F., Fung, Victor S.C.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.07.2019
Subjects:
Adult
Age of Onset
Anemia, Hemolytic - etiology
Dopamine Plasma Membrane Transport Proteins - metabolism
Genetic Diseases, X-Linked - complications
Genetic Diseases, X-Linked - diagnostic imaging
Genetic Diseases, X-Linked - metabolism
Glycolysis
Humans
Juvenile parkinsonism
Male
Metabolism, Inborn Errors - complications
Metabolism, Inborn Errors - diagnostic imaging
Metabolism, Inborn Errors - metabolism
Organotechnetium Compounds
Parkinsonian Disorders - diagnostic imaging
Parkinsonian Disorders - etiology
Parkinsonian Disorders - metabolism
Parkinsonian Disorders - physiopathology
Pathophysiology
Pedigree
Phosphoglycerate Kinase - deficiency
Phosphoglycerate Kinase - metabolism
Putamen - metabolism
Radiopharmaceuticals
Substantia Nigra - diagnostic imaging
Substantia Nigra - metabolism
Tomography, Emission-Computed, Single-Photon
Tropanes
Glycolysis
Pathophysiology
Phosphoglycerate kinase deficiency
Juvenile parkinsonism
ISSN:1353-8020, 1873-5126, 1873-5126
Online Access:Get full text
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Summary:Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined. To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 A > T/p.D164V pathogenic variant. All patients initially presented with infantile-onset encephalopathic and stroke-like episodes, haemolytic anaemia and epilepsy. Two patients had an early-onset and one juvenile-onset levodopa responsive Parkinsonism with motor fluctuations. 99mTc-TRODAT-1 SPECT showed severe bilateral reduced putaminal uptake in the three patients. None of the patients had structural lesions that could explain either pre- or postsynaptic dopaminergic dysfunction. These cases provide strong evidence of a causal relationship between PGK1 deficiency and nigrostriatal pathology causing Parkinsonism. These findings have potential implications for our understanding of the pathophysiology of nigrostriatal degeneration in sporadic PD. •PGK1 deficiency is a differential diagnosis of juvenile or early onset Parkinsonism.•Parkinsonism combined with hemolytic anemia, myopathy, epilepsy and intellectual disability are clues for the disorder.•The Parkinsonism in PGK1 deficiency is associated with severe reduction of putaminal Tc-99m TRODAT SPECT binding.•Parkinsonism in patients with PGK1 deficiency suggest that reduced glycolysis may contribute to nigrostriatal damage.
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ISSN:1353-8020
1873-5126
1873-5126
DOI:10.1016/j.parkreldis.2019.04.004