Genetics and biochemistry of dopa-responsive dystonia: significance of striatal tyrosine hydroxylase protein loss.

Abstract

Notwithstanding the discovery of GCH1 and TH mutations in autosomal-dominant and autosomal-recessive DRD, respectively, a therapeutic trial with levodopa is still the most practical approach to the diagnosis of DRD. The trial needs to be considered in all children with dystonic and/or parkinsonian symptoms or with unexplained gait disorders. Further accumulation of patients with TH-deficient DRD (the mild form of TH deficiency) is necessary to establish the clinical characteristics of this disorder. Regarding GTPCH-deficient DRD, there remain important unresolved issues, including questions of incomplete penetrance of GCH1 mutations, female predominance of affected subjects, and intrafamilial phenotypic variation. A clarification of the mechanism of striatal TH protein loss in GTPCH-deficient DRD may provide a new clue to the pathogenesis of this major form of DRD.

• Authors: Yoshiaki Furukawa
• Journal: Advances in neurology (Adv Neurol) Vol. 91 Pg. 401-10 ( 2003) ISSN: 0091-3952 [Print] United States
• PMID: 12442699 (Publication Type: Journal Article)

Chemical References

• Biopterin
• Dihydroxyphenylalanine
• Tyrosine 3-Monooxygenase
• GTP Cyclohydrolase
• Dopamine
• Homovanillic Acid

Topics

• Animals
• Biopterin (deficiency, genetics)
• Dihydroxyphenylalanine (pharmacology)
• Dopamine (biosynthesis, deficiency)
• Dystonic Disorders (drug therapy, enzymology, genetics)
• GTP Cyclohydrolase (deficiency, genetics)
• Homovanillic Acid (metabolism)
• Humans
• Mutation (genetics)
• Neostriatum (drug effects, enzymology, physiopathology)
• Tyrosine 3-Monooxygenase (deficiency)