BA MD Yanuarita T MD Widagdo S MD Ataxia f ocusing on inherited 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 ID: 774818
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Slide1
Presented by: Vidyaningtyas BA, MDYanuarita T, MDWidagdo S, MD
Ataxia
f
ocusing
on “inherited ataxia”
Slide2Inability 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 .
Ataxia – at glance
Slide3Inability 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 .
Ataxia – at glance
Types:
Cerebellar
ataxia
Sensory
ataxia
Vestibular ataxia
Slide4Inability 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 .
Ataxia – at glance
Types:Cerebellar ataxiaSensory ataxiaVestibular ataxia
Due to dysfunction of the cerebellum. Accompanied by hypotonia, asynergy, dysmetria, dyschronometria, and dysdiadochokinesia.Classified as vestibulocerebellum, spinocerebellum, cerebrocerebellum.
Slide5Inability 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 .
Ataxia – at glance
Types:Cerebellar ataxiaSensory ataxiaVestibular ataxia
Due to dysfunction of the cerebellum. Accompanied by hypotonia, asynergy, dysmetria, dyschronometria, and dysdiadochokinesia.Classified as vestibulocerebellum, spinocerebellum, cerebrocerebellum.
Slide6Inability 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 .
Ataxia – at glance
Types:Cerebellar ataxiaSensory ataxiaVestibular ataxia
due to
loss of proprioception
- the loss of sensitivity to the positions of joint and body
parts
Romberg’s test positive, ataxic hand
Slide7Inability 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 .
Ataxia – at glance
Types:Cerebellar ataxiaSensory ataxiaVestibular ataxia
due to
dysfunction of
vestibular system
,
may be associated
with prominent
vertigo, nausea, vomiting
Slide8Ataxia – at glance
Slide9Ataxia – at glance
As one of the members of chronic symmetrical ataxia which is genetically based
Slide10Harding A (1984)CongenitalMetabolicDefective DNA repairDegenerative
Inherited ataxia
Michelle G et al (2004)Mitochondrial MetabolicDefective DNA repairAbnormal protein folding and degradationChannelopathiesOthers
J
Neurol
2004;251:913-22
Slide11Inherited ataxia
Slide12Harding A (1984)CongenitalMetabolicDefective DNA repairDegenerative
Inherited ataxia
Michelle G et al (2004)Mitochondrial MetabolicDefective DNA repairAbnormal protein folding and degradationChannelopathiesOthers
J Neurol 2004;251:913-22
Mendelian: Autosomal dominant, Autosomal recessive, X-linked
Neuro Sci 2001;21:219-28
Slide13Autosomal recessive
Slide14Commonest form among early onset autosomal recessive ataxia in EuropeDefect at 9q13-q21.1 98% abnormally expanded GAA in 1st intron decreased frataxin expression
Friedreich ataxia
J
Neurol
2004;251:913-22
Slide15Friedreich ataxia
Slide16Commonest form among early onset autosomal recessive ataxia in EuropeDefect at 9q13-q21.1 98% abnormally expanded GAA in 1st intron decreased frataxin expressionPaternal transmission shows contractionClinical manifestation: progressive gait and limb ataxia, dysarthria, absent tendon reflexes, babinski signs, decreased vibration sense, sensory axonal peripheral neuropathy, cardiac hypertrophy, diabetes.
Friedreich ataxia
J
Neurol
2004;251:913-22
Slide17Friedreich ataxia
Slide18Friedreich ataxia
Slide19SCA is the main example.After SCA1 was found in 1993, others named based on number
Autosomal dominant
Slide20Spinocerebellar ataxia
Slide21Spinocerebellar ataxia
Slide22Spinocerebellar ataxia
Slide23Spinocerebellar ataxia
Slide24Spinocerebellar ataxia
Slide25Deficiency of urea cycle enzyme deficiency of ornithine transcarbamylase as the most common hyperammonemia.Lethal in maleFemale: no symptoms – profound neurological impairmentClinical manifestation: irritability, episodic vomiting, ataxia, dysarthria, lethargy, coma, developmental delay, mental retardation, seizure. Treatment: low protein diet, arginine.
X-linked
(metabolic example)
Slide26Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by tremor and cerebellar gait ataxia. caused by moderate expansions of a CGG trinucleotide in FMR1 geneThe pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNAClinical 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 MCPTreatment: low protei n diet, arginine.
X-linked
(FXTAS)
Slide27FXTAS
Slide28Slide29TESTING GUIDELINES
Slide30Slide31Genetic counselling
Recurrence risk
inheritance pattern
The Diagnosis
Molecular test,Prenatal Diagnosis
Slide32Thank You