X‐Linked Levodopa‐Responsive Parkinsonism‐Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review

• Published in: Movement disorders clinical practice (Hoboken, N.J.) Vol. 11; no. 5; pp. 556 - 566
• Main Authors: Guimarães, Thiago Gonçalves, Parmera, Jacy Bezerra, Castro, Matheus Augusto Araújo, Cury, Rubens Gisbert, Barbosa, Egberto Reis, Kok, Fernando
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2024; Wiley Subscription Services, Inc
• Subjects: Adult; Epilepsy; Epilepsy - drug therapy; Epilepsy - genetics; Genetic Diseases, X-Linked - drug therapy; Genetic Diseases, X-Linked - genetics; Humans; Kinases; Levodopa - therapeutic use; levodopa‐responsive parkinsonism; Literature reviews; Male; Middle Aged; Mutation; Parkinson's disease; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - genetics; PGK1; Phosphoglycerate Kinase - genetics; phosphoglycerate kinase‐1; epilepsy; PGK1; Parkinson's disease; levodopa‐responsive parkinsonism; phosphoglycerate kinase‐1
• ISSN: 2330-1619; 2330-1619
• DOI: 10.1002/mdc3.13992

Background
Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene‐specific treatment trials.
Cases
We report 3 X‐linked levodopa (l‐dopa)–responsive parkinsonism‐epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state.
Literature review
Only 8 previous cases have linked this phenotype to PGK1, a gene more commonly associated with hemolytic anemia and myopathy. The unusual association of epilepsy, psychiatric symptoms, action tremor, limb dystonia, cognitive symptoms, and l‐dopa‐responsive parkinsonism must draw attention to PGK1 mutations, especially because this gene is absent from most commercial hereditary parkinsonism panels.
Conclusions
This report aims to shed light on an overlooked gene that causes hereditary parkinsonian syndromes. Further research regarding genetic pathways in PD may provide a better understanding of its pathophysiology and open possibilities for new disease‐modifying trials, such as SNCA, LRRK2, PRKN, PINK1, and DJ‐1 genes.