Dopa-responsive dystonia, DRD-plus and DRD look-alike: a pragmatic review

AbstractDopa-responsive dystonia (DRD) and DRD plus are diseases of the dopamine pathway with sizeable genetic diversity and myriad presentations. DRD has onset in childhood or adolescence with focal dystonia, commonly affecting lower limb, diurnal fluctuations with evening worsening of symptoms and a demonstrable sleep benefit. DRD “plus” has “atypical features” which include infantile onset, psychomotor delay, cognitive abnormalities, oculogyric crisis, seizures, irritability, spasticity, hypotonia, ptosis, hyperthermia and cerebellar dysfunction. Neurodegeneration, however, is not a feature of either DRD or DRD-plus disorders. Tetrahydrobiopterin (BH4), a key cofactor, deficiency leads to inadequate dopamine and serotonin synthesis. Norepinephrine deficiency may coexist, depending on the enzyme defect. Hyperphenylalaninemia (HPA) is a clue for BH4 paucity. However, HPA is conspicuously absent in autosomal-domin ant guanosine triphosphate cyclohydrolase 1 deficiency and sepiapterin reductase deficiency. DRD look-alike is a group of neurodegenerative disorders involving the nigrostriatal dopaminergic system, which could present with dystonia responsive to dopaminergic drugs or neurodegenerative or non-neurod egenerative disorders without involving the nigrostriatal dopaminergic system yet responsive to levodopa. Although levodopa is the mainstay of therapy, response to this drug can be unsatisfactory in DRD plus and DRD look-alike and other drugs are tried. Simultane...
Source: Acta Neurologica Belgica - Category: Neurology Source Type: research