title: Familial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiency.
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.
authors.affiliation: Institute of Neuroscience and Muscle Research, the Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, NSW, Australia. russelld@chw.edu.au
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.forename: Anna
authors.initials: A
authors.lastname: Melchers
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
authors.forename: Padraic
authors.initials: P
authors.lastname: Grattan-Smith
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: John
authors.initials: J
authors.lastname: Earl
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002648:Child; D018389:Codon, Nonsense; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000235:genetics; D004421:Dystonia / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000235:genetics*; D015444:Exercise; D005091:Exons; D005190:Family; D005260:Female; D006136:GTP Cyclohydrolase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000235:genetics; D010375:Pedigree; D012148:Restless Legs Syndrome / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D018389:Codon, Nonsense; D007980:Levodopa; D006136:GTP Cyclohydrolase