Missense variants of human TH are associated with a recessive neurometabolic disease with low levels of brain dopamine and noradrenaline, resulting in a variable clinical picture, from progressive brain encephalopathy to adolescent onset DOPA-responsive dystonia (DRD).
Autosomal recessive mutations in the TH gene cause impaired TH activity and are associated with phenotypes ranging from autosomal recessive dopa-responsive dystonia (DRD) to progressive infantile encephalopathy.
Patients with TH deficiency suffer from progressive infantile encephalopathy dominated by motor retardation similar to a primary neuromuscular disorder, fluctuating extrapyramidal, and ocular and vegetative symptoms.