Three rare GCH1 variants, which were previously reported to be pathogenic in DRD, were found in five patients with PD and not in controls (sequence Kernel association test, p = 0.024).
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).
Results of M-D patients with a pathogenic variant of SGCE were compared to results of idiopathic cervical dystonia (CD) patients, dopa-responsive dystonia (DRD) patients with a pathogenic variant of GCH1 and controls.
The typical clinical presentation of dopa-responsive dystonia, which is also called Segawa disease, is a young age of onset, with predominance in females, diurnal fluctuation of lower limb dystonia, and fair response to low-dose levodopa.
We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a <sup>99m</sup>Tc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation.
"Every child exhibiting dystonia merits an l-dopa trial, lest the potentially treatable condition of dopa-responsive dystonia (DRD) is missed" has been a commonly cited and highly conserved adage in movement disorders literature stemming from the 1980s.
DRD is caused by the mutations in the genes encoding the enzymes involved in the dopamine and tetrahydrobiopterin (BH4) biosynthesis, including the GTP cyclohydrolase 1 (GCH1) gene and the tyrosine hydroxylase (TH) gene.
Mutations in the GCH1 gene are the most common cause of DRD, however, in some cases when the disease is associated with parkinsonism mutations in the PARK2 gene may be identified.
GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.
The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders.
Therefore, we concluded that exonic deletion in the GCH1 gene only accounted for the etiology in a small percentage of patients with sporadic DRD in our Han Chinese cohort.