1. Familial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiency.
- Author
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Dale RC, Melchers A, Fung VS, Grattan-Smith P, Houlden H, and Earl J
- Subjects
- Adult, Age of Onset, Aged, Antiparkinson Agents therapeutic use, Child, Codon, Nonsense, Depressive Disorder cerebrospinal fluid, Depressive Disorder drug therapy, Depressive Disorder genetics, Dystonia cerebrospinal fluid, Dystonia drug therapy, Exons, Family, Female, Humans, Levodopa therapeutic use, Male, Parkinsonian Disorders cerebrospinal fluid, Parkinsonian Disorders drug therapy, Parkinsonian Disorders genetics, Pedigree, Restless Legs Syndrome cerebrospinal fluid, Restless Legs Syndrome drug therapy, Restless Legs Syndrome genetics, Dystonia genetics, Exercise, GTP Cyclohydrolase deficiency, GTP Cyclohydrolase genetics
- Abstract
Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced after many minutes of exercise, and was never present at rest, or on initiation of movements. In addition, family members suffered restless legs syndrome (RLS), depression, and adult-onset Parkinsonism. The index case had low cerebrospinal fluid neurotransmitters and pterins. The PED and RLS stopped on initiation of L-Dopa therapy. Both live family members were found to have a nonsense mutation (p.E84X) in exon 1 of the GTP-cyclohydrolase 1 (GCH-1) gene. We propose that GCH-1 mutations should be considered a genetic cause of familial PED, especially if additional clinical features of monoaminergic deficiency are present in affected individuals.
- Published
- 2010
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