Hugo Morales-Briceño1, Ainhi D Ha2, Kevin London3, David Farlow4, Florence C F Chang5, Victor S C Fung6. 1. Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, Australia. Electronic address: moralhu@gmail.com. 2. Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia. Electronic address: Ainhi.Ha@health.nsw.gov.au. 3. Nuclear Medicine Department, Children's Westmead Hospital, NSW, Australia. Electronic address: kevin.london@health.nsw.gov.au. 4. Nuclear Medicine Department, Westmead Hospital, NSW, Australia. Electronic address: David.Farlow@health.nsw.gov.au. 5. Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia. Electronic address: Florence.Chang@health.nsw.gov.au. 6. Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, Australia. Electronic address: victor.fung@sydney.edu.au.
Abstract
BACKGROUND: 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. OBJECTIVE AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Gabriela Novak; Dimitrios Kyriakis; Kamil Grzyb; Michela Bernini; Sophie Rodius; Gunnar Dittmar; Steven Finkbeiner; Alexander Skupin Journal: Commun Biol Date: 2022-01-13
Authors: Isaac P Heremans; Francesco Caligiore; Isabelle Gerin; Marina Bury; Marilena Lutz; Julie Graff; Vincent Stroobant; Didier Vertommen; Aurelio A Teleman; Emile Van Schaftingen; Guido T Bommer Journal: Proc Natl Acad Sci U S A Date: 2022-01-25 Impact factor: 11.205