Neurodegenerative diseases heterogeneous group of diseases that result

Neurodegenerative diseases • ‘heterogeneous group of diseases that result from specific genetic and biochemical defects or chronic viral infections or varied unknown causes’ • hallmark of a neurodegenerative disease is regression and progressive deterioration of neurologic function

Neurodegenerative diseases NDD Grey matter Convulsion Intellectual impairment Visual impairment White matter UMN sign Progressive spasticity

Grey matter Basal ganglia Wilson disease Huntington’s chorea Haller vorden spatz Cortical storage Non storage Cerebellum Friedrich’s ataxia Ataxia telangectasia

Cortical Non storage With organomegaly Without organomegaly Infantile gauchers Neimann picks Tay Sach’s and its varient Mucopolysaccharidosis GM 1 gangliosidosis GM 2 - Sandhoff Neuronal ceroid lipofusinosis Genetic Leigh, s Menke’s Acquired SSPE HIV

Lysosomal storage dissorders (Lipidoses) • Defective metabolism of sphingolipids in the CNS and visceral organs • Sphingolipids are the cell membrane components and defect in metabolism result in accumulation of substrates within cells leading to alteration of cellular functions • All sphingolipids has common ceramide back bone

GM 1 Gangliosides Β- Galactosidese Globoside GM 1 Gangliosidoses Β- Hexoaminodase A/B Sandhoff GM 2 Ganglioside Β- Hexoaminodase A Tay-sachs Gal-Glc-Ceramide GM 3 Ganglioside α- Galactosidese Fabry (X linked) Gal-Glc-Ceramide Phoshoryl-choline ceramide Sphingomyelinase Β- Galactosidese Glc-Ceramide Neiman pick Β- Galactosidese Krabbe Gal-Ceramide Arylsulfatase H-Gal-Ceramide MLD Ceramidase Goucher Ceramide Farber Ceramidase sphingosine

GM 1 gangliosidosis • • Autosomal recessive Lysosomal storage disorder Generalized accumulation of GM 1 ganglioside Hepatsplenomegaly due to accumulation of foamy histiocytes

Infantile • Around 6/12 • Development regression • Convulsion • Hepatosplenomegaly • Facial dysmorphism • Cherry red spots (50%) • Dysostosis multiplex • Extra sacral mongolian blue spots • Skin eruptions (Angiokeratoma) Juvenile Adult • 3 -4 Yrs (variable) Speech and gait • Ataxia abnormalities • Dysarthria • MR • Spasticity

Dysmorphic features • • • Frontal bossing Depressed nasal bridge and broad nasal tip Large low-set ears Long philthrum Gingival hypertrophy and macroglossia

Dysostosis multiplex • Thickened calvaria, J-shaped enlarged sella turcica

Dysostosis multiplex • flared ilia, acetabular dysplasia and flat femoral heads • wide spatula-shaped ribs

• wide wedge-shaped metacarpals hypoplastic and anteriorly beaked thoracolumbar vertebrae

Other causes for Dysostosis multiplex • • Mucopolysaccharidoses Fucosidosis (Anderson-Fabry) Sialidosis Gangliosidosis

Cherry red spots

Causes of Cherry red spots 1. Tay sachs disease 2. Sandhoff's disease 3. Gaucher's disease 4. Niemann pick's disease 5. CRAO - central retinal artery occlusion 6. Sialodosis 7. Gangliosidoses 8. Metachromatic leukodystrophy 9. Multiple sulfatase deficiency 10. Mucopolisacchridosis

• Diagnosis – acid β -galactosidase activity in peripheral blood leukocytes – Gene test- β -1 galactosidase gene (GLB 1) is available – BP: Vacuolation of lymphocytes • nonspecific indicator • Prenatal diagnosis is possible • No treatment available

GM 2 gangliosidoses -Sandhoff disease • β-Hexosaminidase A deficiency cause Tay. Sachs disease • β-Hexosaminidase A/B deficiency cause Sandhoff disease

GM 1 Gangliosides Β- Galactosidese Globoside GM 1 Gangliosidoses Β- Hexoaminodase A/B Sandhoff GM 2 Ganglioside Β- Hexoaminodase A Tay-sachs Gal-Glc-Ceramide GM 3 Ganglioside α- Galactosidese Fabry (X linked) Gal-Glc-Ceramide Phoshoryl-choline ceramide Sphingomyelinase Β- Galactosidese Glc-Ceramide Neiman pick Β- Galactosidese Krabbe Gal-Ceramide Arylsulfatase H-Gal-Ceramide MLD Ceramidase Goucher Ceramide Farber Ceramidase sphingosine

Infantile • Around 6/12 • Development regression • Convulsion • Hyperacuisis • Macrocephaly • Cherry red spots • Macular pallor • Hepatosplenomegaly • Bony abnormalities Juvenile • 2 -10 Yrs • Ataxia • Dysarthria • MR Adult • Speech and gait abnormalities

• Diagnosis – Hexosaminidase levels in serum, white blood cells, cultured somatic tissues including amniocytes – Gene test • No Rx available

Mx of our patient • • • Seizure control Parental education and counseling Feeding practices Physiotherapy Family planning Follow up

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