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Presented by: Vidyaningtyas BA, MD Yanuarita T, MD Widagdo S, MD Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Types: Cerebellar ataxia Sensory ataxia Vestibular ataxia Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Types: Cerebellar ataxia Sensory ataxia Vestibular ataxia • Due to dysfunction of the cerebellum. • Accompanied by hypotonia, asynergy, dysmetria, dyschronometria, and dysdiadochokinesia. • Classified as vestibulocerebellum, spinocerebellum, cerebrocerebellum. Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Types: Cerebellar ataxia Sensory ataxia Vestibular ataxia • Due to dysfunction of the cerebellum. • Accompanied by hypotonia, asynergy, dysmetria, dyschronometria, and dysdiadochokinesia. • Classified as vestibulocerebellum, spinocerebellum, cerebrocerebellum. Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Types: Cerebellar ataxia Sensory ataxia Vestibular ataxia • due to loss of proprioception - the loss of sensitivity to the positions of joint and body parts • Romberg’s test positive, ataxic hand Inability to make smooth, accurate and coordinated movements, usually due to a disorder of the cerebellum and / or sensory pathways in the posterior column of the spinal cord . Types: Cerebellar ataxia Sensory ataxia Vestibular ataxia • due to dysfunction of vestibular system, • may be associated with prominent vertigo, nausea, vomiting Ataxia Symmetrical Acute Asymmetrical Chronic Inherited ataxia Acute Chronic Ataxia Symmetrical Acute Asymmetrical Chronic Inherited ataxia Acute Chronic • As one of the members of chronic symmetrical ataxia which is genetically based Harding A (1984) Congenital Metabolic Defective DNA repair Degenerative J Neurol 2004;251:913-22 Michelle G et al (2004) Mitochondrial Metabolic Defective DNA repair Abnormal protein folding and degradation Channelopathies Others Harding A (1984) Congenital Metabolic Defective DNA repair Degenerative J Neurol 2004;251:913-22 Michelle G et al (2004) Mitochondrial Metabolic Defective DNA repair Abnormal protein folding and degradation Channelopathies Others Mendelian: Autosomal dominant, Autosomal recessive, X-linked Neuro Sci 2001;21:219-28 Commonest form among early onset autosomal recessive ataxia in Europe Defect at 9q13-q21.1 98% abnormally expanded GAA in 1st intron decreased frataxin expression J Neurol 2004;251:913-22 Commonest form among early onset autosomal recessive ataxia in Europe Defect at 9q13-q21.1 98% abnormally expanded GAA in 1st intron decreased frataxin expression Paternal transmission shows contraction Clinical manifestation: progressive gait and limb ataxia, dysarthria, absent tendon reflexes, babinski signs, decreased vibration sense, sensory axonal peripheral neuropathy, cardiac hypertrophy, diabetes. J Neurol 2004;251:913-22 SCA is the main example. After SCA1 was found in 1993, others named based on number Deficiency of urea cycle enzyme deficiency of ornithine transcarbamylase as the most common hyperammonemia. Lethal in male Female: no symptoms – profound neurological impairment Clinical manifestation: irritability, episodic vomiting, ataxia, dysarthria, lethargy, coma, developmental delay, mental retardation, seizure. Treatment: low protein diet, arginine. Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor and cerebellar gait ataxia. caused by moderate expansions of a CGG trinucleotide in FMR1 gene The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA Clinical manifestation: intention tremor, cerebellar gait and limb ataxia, parkinsonism,decreased reflexes, orthostatic hypotension, impotence, progressive loss of bowel and bladder control. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in neurons and astrocytes throughout the brain increased T2 signal intensity in white matter of the MCP Treatment: low protei n diet, arginine. The Diagnosis inheritance pattern Genetic counselling Molecular test,Prenatal Diagnosis Recurrence risk