<unk>  deficiency leads to impaired synthesis of dopamine as well as epinephrine and norepinephrine. It is represented by a progressive encephalopathy and poor prognosis. Clinical features include dystonia<unk> at is minimally or nonresponsive to levodopa, extrapyramidal symptoms, ptosis, miosis, and postural hypotension.<unk> is is a progressive and often lethal disorder, which can be improved but not cured by levodopa. Due to<unk> e low number of patients and overlapping symptoms with other disorders, early diagnosis and treatment remain challenging. Response to treatment is variable and<unk> e long-term and functional outcome is unknown. To provide a basis for improving<unk> e understanding of<unk> e epidemiology, genotype/phenotype correlation and outcome of<unk> ese diseases<unk>  impact on<unk> e quality of life of patients, and for evaluating diagnostic and<unk> erapeutic strategies a patient registry was established by<unk> e noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD). Additionally alterations in<unk> e<unk>  enzyme activity may be involved in disorders such as Segawa's dystonia, Parkinson's disease and schizophrenia.<unk>  is activated by phosphorylation dependent binding to 14-3-3 proteins. Since<unk> e 14-3-3 proteins also are likely to be associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease, it makes an indirect link between<unk>  and<unk> ese diseases.<unk> e activity of<unk>  in<unk> e brains of patients with Alzheimer’s disease has been shown to be significantly reduced compared to healthy individuals.<unk>  is also an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I. A consistent abnormality in Parkinson's disease is degeneration of dopaminergic neurons in<unk> e substantia nigra, leading to a reduction of striatal dopamine levels. As<unk>  catalyzes<unk> e formation of L-DOPA,<unk> e rate-limiting step in<unk> e biosynthesis of dopamine,<unk> -deficiency does not cause Parkinson's disease, but typically gives rise to infantile parkinsonism, although<unk> e spectrum extends to a condition resembling dopamine-responsive dystonia. A direct pathogenetic role of<unk>  has also been suggested, as<unk> e enzyme is a source of H2O2 and other reactive oxygen species (ROS), and a target for radical-mediated injury. It has been demonstrated<unk> at L-DOPA is effectively oxidized by mammalian<unk> , possibly contributing to<unk> e cytotoxic effects of L-DOPA. Like other cellular proteins,<unk>  is also a possible target for damaging alterations induced by ROS.<unk> is suggests<unk> at some of<unk> e oxidative damage to<unk>  could be generated by<unk> e<unk>  system itself.<unk>  can be inhibited by<unk> e drug α-methyl-para-tyrosine (metirosine).<unk> is inhibition can lead to a depletion of dopamine and norepinepherine in<unk> e brain due to<unk> e lack of<unk> e precursor L-Dopa (L-3,4-dyhydroxyphenylalanine) which is synthesized by<unk> .<unk> is drug is rarely used and can cause depression, but it is useful in treating pheochromocytoma and also resistant hypertension. Older examples of inhibitors mentioned in<unk> e literature include oudenone and aquayamycin.
Tyrosine hydroxylase
Dopamine beta-hydroxylase
Phenylalanine hydroxylase
Catechol-O-methyltransferase
Aromatic L-amino acid decarboxylase
Monoamine oxidase
Glutamate dehydrogenase
Monoamine oxidase B