DOPA Responsive Dystonia Due to GTP Cyclohydrolase -1 Deficieny Caused by PTS Gene Mutation
Journal of Medical Science And clinical Research
Dopa-responsive dystonia (DRD) is a childhood-onset dystonic disorder, Characteristic symptoms include dystonia typically absent in the morning or after rest but worsening during the day and with exertion. Few patients may present with signs of Parkinsonism that may include bradykinesia, rigidity, balancing difficulties, and postural instability. The striking feature of this disorder is gradual progression to generalised dystonia without significant involvement of autonomic and sensory system.
... nd sensory system. Intellect also remain remarkably unaffected. Though the features typically present in first decade of life there are cases which have been reported in later decades of life. The diagnosis is usually established in patients having typical clinical features responding dramatically to oral administration of levodopa. The confirmation of diagnosis depends upon confirming mutation involving the PTS (pyruvoyl tetrahydropterin synthase) gene (Chr11:112104186; G>T). Though genetic testing is required for confirmation of diagnosis more than 25% of patients with DRD do not show the common mutations. Some of these coding region mutation-negative cases may be due to sporadic mutations, autosomal recessive variety of DRD and TH-deficient DRD. Gene deletions, De novo mutations and incomplete penetrance may be responsible for sporadic cases. In minority of the cases metabolism of dopamine is altered but their neurological functions remain normal and these patients may behave like asymptomatic carriers of mutated genes. Here by we present a case of DRD in a 7 year old male child with dystonic tremors and bradykinesia and was proven to have homozygous missense variation in exon 6 of the PTS gene ( Chr11:112104186 ; G>T) that results in the amino acid substitution of Tyrosine for Aspartic acid at codon 116(p.D116Y; ENST00000280362). The patient responded well to L-Dopa.