Novel GCH-1 mutations and unusual long-lasting dyskinesias in Korean families with dopa-responsive dystonia

Lee, Jee Young; Yang, Hee Joon; Kim, Jong Min; Jeon, Beom S.

doi:10.1016/j.parkreldis.2013.08.003

Cited by 11 publications

(9 citation statements)

References 11 publications

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“…Indeed they tend to appear at the beginning of the treatment and subside after dose reduction without reoccurring with subsequent slow dose increase (Furukawa et al , 2004; Lee et al , 2013). Second, we could not determine at the individual level the effect on pterin and dopamine metabolism of the GCH1 variants detected in the exome sequencing study.…”

Section: Discussionmentioning

confidence: 99%

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Mencacci

Isaias

Reich

et al. 2014

Brain

176

134

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Section: Discussionmentioning

confidence: 99%

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Mencacci

Isaias

Reich

et al. 2014

Brain

176

134

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“…24,25 In a study of 19 patients with GCH1 mutations, one patient had residual symptoms of facial grimacing and upper-limb dystonia. 26 Another study reported a high frequency of residual motor signs in patients who were receiving levodopa therapy: 28% of patients who were identified in a literature review, and 39% of patients in a pilot study group. 24 In some individuals, especially those with spasmodic dysphonia, even doses of up to 600 mg daily might produce an incomplete response.…”

Section: Treatmentmentioning

confidence: 99%

“…19,[20][21][22][23][24][25][26] The disease typically presents between infancy and adolescence. In one series of 28 patients, the average age of onset was 6.9 ± 2.9 years (except for one patient in whom the onset of symptoms occurred at age 54 years).…”

Section: Introductionmentioning

confidence: 99%

Dopa-responsive dystonia—clinical and genetic heterogeneity

2015

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Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment.

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“…We would like to note that the penetrance of the GCH-1 mutation is only 30 % supporting that the presence of a mutation does not guarantee clinical symptoms and a diagnosis of DRD [14], and that L-dopa response is so excellent in the most severely affected DRD cases after many years of treatment delay [25] that it is hard to imagine that mild clinical symptoms may be the only and residual symptoms. In our recent report of 19 cases of GCH-1 mutation positive DRD, only 1 case (Case III: 2 in family D) had residual symptoms with facial grimacing and upper limb dystonia [82•]. Of interest is that her brother (case III:1) had isolated torticollis, which did not respond to L-dopa.…”

Section: Considerations For Diagnosismentioning

confidence: 99%

“…However, we failed to find mutations in GCH-1 at the time of the report. A recent analysis showed that Family C has exon1 P95R (nt284C > G) and Patient 9 (S4 in Lee et al, 2013) has Gly203Arg [82•]. In addition, a case by Nagata et al is a perfect example of DRD-plus with a GCH-1 mutation suspected but not found [90].…”

Section: Considerations For Diagnosismentioning

confidence: 99%

Clinical Spectrum of Dopa-Responsive Dystonia and Related Disorders

Lee

Jeon

2014

Curr Neurol Neurosci Rep

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Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study.Electronic supplementary materialThe online version of this article (doi:10.1007/s11910-014-0461-9) contains supplementary material, which is available to authorized users.

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Novel GCH-1 mutations and unusual long-lasting dyskinesias in Korean families with dopa-responsive dystonia

Cited by 11 publications

References 11 publications

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers

Dopa-responsive dystonia—clinical and genetic heterogeneity

Clinical Spectrum of Dopa-Responsive Dystonia and Related Disorders

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