DYSTONIA

The molecular defect of autosomal dominant dopa-responsive dystonia (DRD) is GTP cyclohydrolase-1 (GTPCH-1) deficiency (the first enzymatic step in the synthesis of tetrahydrobiopterin, the cofactor for tyrosine hydroxylase). This, along with the postmonem examination showing lack of degeneration in the substantia nigra and in the striatum, strongly identifies DRD as a neurochemical disease ra.ther than a neurodegenerative disease. Discovery of the enzymattc defect came about via molecular genetics, first with the mapping of the gene defect of this disorder on chromosome 14q, and then with finding the mutations in the gene that codes for GTPCH-1. This demonstrates the power of molecular genetics. Different mutations of the gene affect different families. It is likely that there may be separate mutations of other genes coding for the other enzymes involved in the synthesis of tetrahydrobiopterin.