hdl like illness.

Slide 3: 

In a 1908 review, eminent physician William osler said of the paper ‘In the history of medicine ,there are few instances in which disease has been more accurately, more graphically or more briefly described.’

MUTANT HUNTINGTIN INCLUSIONS. : 

MUTANT HUNTINGTIN INCLUSIONS.

Slide 5: 

Most important genetic cause of chorea is Huntingtons chorea Caused mutation of IT15(huntingtin) on short arm of chromosome 4 with expansion of CAG repeats. Characterized by adult onset personality changes ,generalized chorea and cognitive decline

Slide 6: 

Children/adolescent(westphal variant) or akinetic rigid syndrome. Oculomotor abnormalities like Impersistence of gaze ,difficulty initiating saccades Dysarthria,dysphagia Pyramidal signs Ataxia Dystonia,myoclonus,tics.tremors

Slide 7: 

Stevanin et al in 2002 Study of 618 patients, 93% of the patients had HD like trinucleotide expansion. What about the rest?????

Sadly insanes do baghdad!! : 

Sadly insanes do baghdad!!

Slide 9: 

Clinician need to be aware of increasing range of differential diagnosis when confronted with a clinical situation of Slowly progressive adult onset chorea Family h/o neurological or psychiatric illness.

Slide 10: 

HDL 1 Autosomal dominant 192 or 168 base pair insertion in prion protein region on chromosome 20. Similar clinical picture, ocassional seizure Age 20-45 years Imaging- atrophy of frontal lobe,basal ganglia with cerebellum Neuropathological examination- multicentric plaques staining with antiprion antibodies. Krause et al..

Slide 11: 

HDL-2 2% of HD without IT15 mutation South africa Rare in white & japanese population 3rd-4th decade Juvenile onset variant- no eye abnormality,no seizures.

Slide 12: 

10% HDL2 –acanthocytes. CTG-CAG triplet repeat expansion in junctophillin 3 gene on chromosome 16. Normal- 6-28 Pathogenic- 44-57 Pathogenicity due to mRNA inclusion.

Slide 13: 

HDL3 Saudi Arabia Autosomal recessive Age 3-4 years Early onset mental retardation Dysarthria, dystonia ,pyramidalsign ,ataxia and gait impairment Age of onset and pattern of inheritance?? AL-Tahan et al &Kambouris et al

Slide 14: 

HDL-4 (SCA-17) Mutation of TATA box binding protein (TBP) Chromosome 6 CAA.CAG repeats n <42.pathogenic(45-66) Age -19 to 48 years.

Slide 15: 

Cerebellar ataxia- 94% Extrapyramidal -73% Pyramidal -37% Epilepsy -22% Dementia -76% Psychiatric -27%

Slide 16: 

Degenration of gray matter of cerebellum Reduced dopamine transporter activity Associated atrophy of hippocampus, basal ganglia, neocortex. Normal electrophysiological studies for ataxia SSEP- absence of p14 and p31 waves.

Other AD disoder : 

Other AD disoder DRPLA-dentatorubral-pallidoluysian atrophy. Atrophin 1 gene mutation on chromosome12 Polyglutamine stretch(CAG) normally 7-25. Pathogenic-49-88. Instabilty during tranmission

Three clinical phenotypes,with an average age at onset between 20 and 30 years, : 

Three clinical phenotypes,with an average age at onset between 20 and 30 years, prominent chorea similar to HD, prominent ataxia, prominent myoclonus. Severe progressive myoclonus epilepsy and cognitive decline has been described in early onsetcases. Late-onset disease can present with mild cerebellar ataxia.

Slide 19: 

Death within next 20 years. Predominant in japan. Degeneration of dentate and red nuclei,Globus pallidus, substantia nigra.

Neuroferritinopathy : 

Neuroferritinopathy Autosomal dominant FTL gene mutation codes for ferritin light polypeptide Chromosome-19 Cumbrian region of UK due to founder effect. 40 years Extrapyramidal features like chorea ,dystonia with predominant oromandibular dyskinesias

Slide 21: 

Parkinsonism without tremor Frontal lobe syndrome MRI T2 * weighted imaging may show accumulation of iron in basal ganglia even in asymptomatic individuals. Skeletal muscle biopsy : abnormalities of mitochondrial respiratory chain Low serum ferritin levels.

Slide 22: 

doi:10.1093/brain/awl319 Brain (2007), 130, 110–1 Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation Patrick F. Chinnery,1,2 Douglas E. Crompton,1,2 Daniel Birchall,3 Margaret J. Jackson,2 Alan Coulthard,3,8 Anne Lombe`s,9 Niall Quinn,4 Adrian Wills,5 Nicholas Fletcher,6 John P. Mottershead,7 Paul Cooper,7 Mark Kellett,7 David Bates2 and John Burn

Selected AR disorder : 

Selected AR disorder Choreoacanthocytosis Neurodegeneration of basal ganglia Mutation of vacuolar protein sorting 13 homolog A (VPS13A) coding for chorein on chromosome 9q21 Young adulthood Orofacial dystonia , chorea ,tics, parkinsonism,eye movement abnormalities,Subcortical dementia ,Self mutilation

Slide 26: 

Myopathy Neuropathy Peripheral smear showing acanthocytes Progressive caudate atrophy Extensive neuronal loss and gliosis affecting striatum, substantia nigra post mortem.

Pantothenate kinase associated neurodegeneration : 

Pantothenate kinase associated neurodegeneration Hallvorden-spatz/ Neurodegeneration with brain iron accumulation (NBIA 1) 3-4 years Chromosome 20 Generalized dystonia parkinsonism

Slide 28: 

Pigmentary retinal degeneration Atypical - late onset slowly progressive. chorea in adult onset With similar clinical features and MRI s/o iron deposition but without PANK2 mutation do not show eye of tiger appearance.

Slide 29: 

PLA2G6 Mutation on chromosome 22 Calcium independent phospholipase Pyramidal features Infantile neuroaxonal dystrophy Spastic tetraplegia Visual impairment Cerebellar atrophy( karak syndrome)

Slide 30: 

Acanthocytes are found in the blood in approximately 10% of PKAN cases, and are possibly related to abnormalities of lipid metabolism. Some cases of PKAN with acanthocytes and additional features such as hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration were given the acronym HARP syndrome. .

Slide 31: 

In addition to the classic neuroacanthocytosis syndrome, the diagnosis of PKAN should also, therefore, be considered if acanthocytes are found in a patient with chorea

X linked Mcleod syndrome : 

X linked Mcleod syndrome Neuroacanthocytosis syndrome—is clinically similar to chorea–acanthocytosis, with seizures, peripheral neuropathy and myopathy, and can also present with an HDL phenotype Elevated liver enzyme and creatine kinase Absence of kx antigen & reduced kell antigen on erythrocytes Cardiomyopathy and arrythmia causing sudden death.

Treatment for the HDL disorders is symptomatic : 

Treatment for the HDL disorders is symptomatic Tetrabenazine or dopamine-receptor-blocking agents can alleviate the chorea. More disabling for the patient, however, can be the psychiatric features and mood disturbances associated with the disorders, in which case antidepressants might be indicated. .

Slide 36: 

Genetic counseling is recommended on the basis of the molecular diagnosis. The support of social services and ancillary agencies, as well as occupational therapy, speech therapy and physiotherapy, are important components of treatment, and should not be neglected

WOODY GUTHRIE (1912-1967) : 

WOODY GUTHRIE (1912-1967)