tay sach disease physilogy and biochemistry

all about the tay sach disease

1. Tay-Sachs Disease Ananya Dwivedi MBBS Student (2022 batch)

2. The History Warren Tay and Bernard Sachs discovered the Tay-Sachs disease. Bernard Sachs was a neurologist who first described the changes in the brain and the prevalence among Ashkenazi Jews. Discovered in 1880 Mainly discovered in European countries Autosomal Recessive Carriers 1/30 of Ashkenazi ancestry 1/50 Irish ancestry (?) 1/53 French Canadians 1/300 non Ashkenazi

3. ER Stress In healthy cells, newly synthesized proteins are folded in the ER with the help of chaperones and are then incorporated into the cell or secreted. ER Stress: cell is unable to cope with the load of misfolded proteins. Accumulation of these proteins in the ER triggers the unfolded protein response, which tries to restore protein homeostasis; if this response is inadequate, the unfolded protein response actively signals apoptosis

4. Lysosomal Storage Diseases Gangliosides are degraded by a set of lysosomal enzymes that catalyze the stepwise removal of sugar units from the head group, finally yielding a ceramide

5. GM2 gangliosides Mutation in these gene leads to accumulation of GM2 gangliosides -similar phenotypic effects Tay Sach Ds. most common form of GM2 gangliosidosis M utations in the α-subunit locus on chr. 15 S evere deficiency of hexosaminidase A

6. TAY SACHs DISEASE E specially prevalent among Jews Eastern European (Ashkenazic) origin (Carrier rate 1 in 30) >100 mutations in HEXA α-subunit gene , mostly affecting protein folding Antenatal diagnosis and carrier detection are possible by enzyme assays and DNA-based analysis.

7. Retina: Cherry Red Spot Fundus photograph of the cherry-red spot in Tay-Sachs disease The ganglion cells in the retina swollen with GM2 ganglioside, particularly at the margins of the macula Photomicrograph of the macula (periodic acid–Schiff stain) The presence of ganglion cells filled with gangliosides outside the fovea blocks the transmission of the normal orange-red color of the choroid, but absence of ganglion cells within the fovea (to the right of the vertical bar) permits the normal orange-red color to be visualized, accounting for the so-called cherry-red spot.

8. Tay Sachs Histology (Neuron) Ganglion cell (light microscope), a large neuron has obvious lipid vacuolation S everal types of cytoplasmic inclusions Most common is prominent lysosomes with whorled configurations , onion-skin layers of membranes (electron microscope)

9. Detection Methods Amniocentesis (@16 th week of pregnancy) Chorionic villus sampling (@10 th week of pregnancy) Blood samples to detect carriers

10. Symptoms Start from 3 to 6 month from birth. Deafness Hard time breathing Seizure Blindness Slow growth Macrocephaly The nerve damage leads to seizures, which may result in choking or physical injury.

11. Treatment E nzyme replacement therapy C ell transplantation S ubstrate reduction therapy E nzyme enhancing therapy G ene therapy Bone Marrow Transplant Supportive and psychotherapy

12. Clinical Course