Rare and Disabling Movement Disorders: An Indian Experience

Recent decades have seen exciting developments in the field of movement disorders. These include identification of rare clinical syndromes and use of technological advances to understand their pathogenesis. Three such disorders are discussed here. The description of the Uner Tan syndrome from Turkey and surrounding regions provoked research into the controversial field of genetically induced devolution. Such cases with few additional findings have now been described from India. Sepiapterin reductase deficiency is a rare treatable autosomal recessive form of dopa responsive dystonia. Indian literature has recently added five confirmed cases to the international database. Such cases are eminently treatable. Successful application of modern technology in understanding the pathogenesis of progressive neurodegenerative disorder has been highlighted in the section on hereditary spastic paraplegias. Hitherto undescribed subcellular organelle transport defects and their potential rectification with known drugs have been demonstrated raising hopes for their cure

Spinocerebellar ataxia type 7: Report of an Indian family

Spinocerebellar ataxia type 7 (SCA7) is a form of autosomal dominant cerebellar ataxia which is associated with pigmentary retinal degeneration. It is known for its world-wide rarity except in the Scandinavian countries. It is very rarely reported from India and the neighbouring Asian countries . The present report describes the neurogenetic findings of a family of SCA7, from the northern part of Karnataka in South India. It documents the wide intrafamilial phenotypic variability, which could be correlated with the CAG repeat counts and phenomenon of anticipation. Genotype phenotype correlation highlighted certain disparities in comparison with the previous studies. The report highlights the need for multiethnic population studies and the role of genetic counseling and prenatal testing in SCA7 patients

Acute movement disorder with bilateral basal ganglia lesions in diabetic uremia

Acute movement disorder associated with symmetrical basal ganglia lesions occurring in the background of diabetic end stage renal disease is a recently described condition. It has distinct clinico-radiological features and is commonly described in Asian patients. We report the first Indian case report of this potentially reversible condition and discuss its various clinico-radiological aspects

A Compound Heterozygote for GCH1 Mutation Represents a Case of Atypical Dopa-Responsive Dystonia.

peer reviewedDopa-responsive dystonia (DRD), a movement disorder, is characterized by young onset dystonia and dramatic response to levodopa treatment. However, the wide range of phenotypic spectrum of the disease often leads to misdiagnosis. DRD is usually caused by mutation in GCH1 gene coding for GTP cyclohydrolase 1 (GTPCH1) enzyme, which is involved in biosynthesis of tetrahydrobiopterin (BH4) and dopamine. In this study, the entire GCH1 gene was screened in 14 Indian DRD patients and their family members. A family was identified where the proband was found to be a compound heterozygote for GCH1 (p.R184H and p.V204I) variants; the former variant being inherited from the father and the latter from the mother. All other family members harboring one of these GCH1 variants were asymptomatic except for one (heterozygous for p.R184H) who was diagnosed with DRD. In silico analyses predicted these two variants to be pathogenic and disruptive to GCH1enzymatic activity. This proband was misdiagnosed as cerebral palsy and remained untreated for 25 years. He developed retrograde movements and gait problems in lower limbs, deformity in upper limbs, and difficulty in swallowing, and became mute. However, most of his symptoms were alleviated upon levodopa administration. Our study confirms the variability of DRD phenotype and the reduced penetrance of GCH1 mutations. It also emphasizes the need of molecular diagnostic test and L-dopa trial especially for those with atypical DRD phenotype