Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome

Leuzzi, Vincenzo; Carducci, Ca.; Carducci, Cl.; Cardona, Francesco; Artiola, Cristiana; Antonozzi, I.

doi:10.1212/wnl.59.8.1241

Cited by 65 publications

(42 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The P23L mutation in the GCH1 allele was previously described in four different families 17,18 . It is particularly interesting the fact that this sequence change was previously detected in a patient with DRD combined with another mutation, suggesting that P23L could represent a rare polymorphism in the population or, alternatively, that this mutation could only be pathogenic in association with another mutation, as in our case 18 .…”

Section: Discussionmentioning

confidence: 99%

A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia

Scola

Carducci

Amaral

et al. 2007

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

-Dopa-responsive dystonia (DRD) is an inherited metabolic disorder now classified as DYT5 with two different biochemical defects: autosomal dominant GTP cyclohydrolase 1 (GCH1) deficiency or autosomal recessive tyrosine hydroxylase deficiency. We report the case of a 10-years-old girl with progressive generalized dystonia and gait disorder who presented dramatic response to levodopa. The phenylalanine to tyrosine ratio was significantly higher after phenylalanine loading test. This condition had two different heterozygous mutations in the GCH1 gene: the previously reported P23L mutation and a new Q182E mutation. The characteristics of the DRD and the molecular genetic findings are discussed.KEY WORDS: dystonia, levodopa, dopa-responsive dystonia, guanosine triphosphate cyclohydrolase 1, GCH1 gene. Novo padrão de mutação missense no gene GCH1 na distonia dopa-responsivaRESUMO -Distonia dopa-responsiva (DRD), classificada como DYT5, é um erro inato do metabolismo que pode ser causado por dois diferentes tipos de defeito bioquímico: deficiência de GTP ciclo-hidrolase 1 (GCH1) (autossômica dominante) ou de tirosina hidroxilase (autossômica recessiva). Descrevemos o caso de menina de 10 anos com distonia generalizada progressiva e alteração da marcha com importante melhora após uso de levodopa. A relação fenilalanina/tirosina estava aumentada após teste de sobrecarga com fenilalanina. O estudo molecular mostrou que o paciente apresenta uma combinação hererozigótica de mutação no gene GCH1: a já conhecida mutação P23L e uma nova mutação Q182E. Discutem-se as características da DRD e as alterações genéticas possíveis.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia

Scola

Carducci

Amaral

et al. 2007

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…One notes a kindred presenting with autosomal dominant clinical features of myoclonus dystonia syndrome who was found to have GTP cyclohydrolase I deficiency, which is typically associated with dopa-responsive dystonia. 6 The pathophysiology of myoclonus dystonia is unknown.…”

Section: Go To Sectionmentioning

confidence: 99%

Clinical Reasoning: A 13-year-old boy presenting with dystonia, myoclonus, and anxiety

Blackburn¹,

Cirillo²

2012

Neurology

View full text Add to dashboard Cite

“…4 This genotype has been reported previously in association with dystonia and parkinsonism. 5 Interestingly, this mutation 1 Medical School, Newcastle University, Newcastle-upon-Tyne, United Kingdom; 2 Department of Neurology, Newcastle Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom has also previously been reported by Leuzzi et al, 6 who describe a childhood-onset myoclonus dystonia-like syndrome resulting from GCH1 mutations, with other family members having adult-onset upper-limb tremor. They do not, however, describe alcohol sensitivity.…”

Section: Discussionmentioning

confidence: 58%