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

Abstract

AbstractBackgroundGenetic 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.CasesWe 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 reviewOnly 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.ConclusionsThis 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.