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Clinical spectrum of dopa-responsive dystonia and related disorders.

Lee WW, Jeon BS - Curr Neurol Neurosci Rep (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Movement Disorder Center, CRI, Seoul National University Hospital, Seoul, Korea.

ABSTRACT
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.

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Related in: MedlinePlus

Diagnostic flow for dopa-responsive dystonia and related disorders
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Related In: Results  -  Collection


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Fig2: Diagnostic flow for dopa-responsive dystonia and related disorders

Mentions: If the clinical diagnosis is DRD, then genetic screening of GCH-1 is the most productive (Fig. 2). If GCH-1 screening is negative, the CSF neopterin and biopterin levels will guide the investigation to the individual enzymes in BH4 metabolism and TH. If the CF neopterin is low, an exhaustive study of GCH-1 is needed, whereas a normal CSF neopterin level will necessitate examination of other genes in BH4 metabolism and TH but not in GCH-1. A similar diagnostic algorithm is also logical in DRD-plus. DAT imaging will reliably screen DRD-mimicking JPD. Of note is the recent discovery of DAT and VMAT deficiency syndromes [76••, 77••]. These rare AR genetic disorders have DRD-plus features of hypo- and hyperkinetic movement disorder and ocular motility problems with onset in infancy. The DAT deficiency syndrome had raised ratios of HVA to 5-HIAA in the CSF. DAT imaging showed a complete loss of DAT activity in the basal nuclei. If the patient with the characteristics of DRD-plus has no abnormalities of the neurotransmitters and metabolites in the CSF, the diagnosis of that patient could be VMAT2 deficiency [77••]. VMAT2-deficient patients show abnormal neurotransmitters and metabolites only in the urine.Fig. 2


Clinical spectrum of dopa-responsive dystonia and related disorders.

Lee WW, Jeon BS - Curr Neurol Neurosci Rep (2014)

Diagnostic flow for dopa-responsive dystonia and related disorders
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4061475&req=5

Fig2: Diagnostic flow for dopa-responsive dystonia and related disorders
Mentions: If the clinical diagnosis is DRD, then genetic screening of GCH-1 is the most productive (Fig. 2). If GCH-1 screening is negative, the CSF neopterin and biopterin levels will guide the investigation to the individual enzymes in BH4 metabolism and TH. If the CF neopterin is low, an exhaustive study of GCH-1 is needed, whereas a normal CSF neopterin level will necessitate examination of other genes in BH4 metabolism and TH but not in GCH-1. A similar diagnostic algorithm is also logical in DRD-plus. DAT imaging will reliably screen DRD-mimicking JPD. Of note is the recent discovery of DAT and VMAT deficiency syndromes [76••, 77••]. These rare AR genetic disorders have DRD-plus features of hypo- and hyperkinetic movement disorder and ocular motility problems with onset in infancy. The DAT deficiency syndrome had raised ratios of HVA to 5-HIAA in the CSF. DAT imaging showed a complete loss of DAT activity in the basal nuclei. If the patient with the characteristics of DRD-plus has no abnormalities of the neurotransmitters and metabolites in the CSF, the diagnosis of that patient could be VMAT2 deficiency [77••]. VMAT2-deficient patients show abnormal neurotransmitters and metabolites only in the urine.Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Movement Disorder Center, CRI, Seoul National University Hospital, Seoul, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus