Juvenile onset parkinsonism-dystonia syndrome: A novel mutation in the SLC6A3 gene

Abstract

The differential diagnosis for genetic dystonia parkinsonism is broad. Juvenile onset parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive disorder with variable neurological manifestations and age of onset. We describe DTDS with a novel mutation. Case report We identified a 19-year-old male, who presented with history of juvenile-onset parkinsonism. He had a normal birth and neonatal course with normal developmental milestones. Cognitive, motor and speech were reported to be normal in the first decade of life. At 10–11 years of age, the patient started to have tremor and progressive parkinsonian symptoms. He additionally starts to have speech difficulties. The parents are consanguineous, but there is no family history of movement disorders, Parkinson’s disease or other psychiatric illness. Other siblings (brother and sister) are unaffected. Neurological examination revealed loss of speech to single words, rigidity, generalized bradykinesia, dystonia with dystonic tremor. Gene analysis showed a novel homozygous mutation in SLC6A3 gene (g.1394863c > G) with both parents and siblings having a heterozygous mutation in the same gene. •DTDS is a rare disorder that should be considered in the differential diagnosis of genetic parkinsonism of juvenile-onset. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea with parkinsonian features.•Atypical onset in adolescence or adulthood has been described.•SLC6A3 encodes the dopamine transporter (DAT) that is expressed predominantly within the substantia nigra and in the midbrain, which has a crucial role in mediating reuptake and homeostasis of dopamine.