Abstract
Dopa-responsive dystonia (DRD) comprises a group of rare autosomal inherited neurotransmitter disorders characterized with childhood or adulthood onset. We report three cases of DRD. Two boys (1.5-year-old and 1.3-year-old) were diagnosed with TH deficiency and found to have compound heterozygous missense variants in the TH gene. For the first patient p.Arg202His and the p.Leu205Pro in the TH gene, were reported. In the second patient were revealed p.Thr373Met and p.Arg202His variants in the same gene. The third patient, a 10-years old boy was diagnosed with GCH1 deficiency due to heterozygous pathogenic variant (p.Lys224Arg) in the GCH1 gene. The diagnosis of DRD was determined by whole exome sequencing (Patient 1) and whole genome sequencing (Patients 2 and 3). Here, we describe the first two patients with TH deficiency in Bulgaria and one with GCH1 deficiency. We also review the molecular mechanism of the disorder and summarized the reported pathogenic or likely pathogenic variants in the TH and GCH1 genes. The disorder has broad clinical and genetic heterogeneity which is often misdiagnosed. Our aim is to improve awareness for the DRD, especially in Bulgaria because early diagnosis is essential for the better prognosis and therapy outcome.