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| Tay-Sachs Disease: | |||||||||||||||||||||||||||
| Genetic Disorder - autosomal recessive, meaning both parents have to be carrier of the disease. Mutation still around because the heterozygous enjoys decreased risk towards tuberculosis | |||||||||||||||||||||||||||
| Causes Gangliosidosis, which is a group of 3 lysosomal storage disease. It is caused by the inability to catabolize GM2 gangliosides. Degradation of GM2 requires 3 polypeptides encoded by 3 separate loci. | |||||||||||||||||||||||||||
| Phenotypic effects of mutations in these genes are similar, because they all result in the accumulation of GM2 gangliosides. The molecular enzyme defect however varies in the 3. | |||||||||||||||||||||||||||
| Tay-Sachs is the most common GM2 gangliosidosis. It results from a mutation in the alpha - subunit locus chromosome 15 and causes severe hexosaminidase A deficiency.�� | |||||||||||||||||||||||||||
| Absence of hexosaminidase A in virtually all tissues including leukocytes and plasmacytes. This therefore causes accumulation of GM2 gangliosides in those tissues(heart, spleen, liver?) | |||||||||||||||||||||||||||
| Involvement of neurons in the CNS and ANS and retina are dominant clinical picture | |||||||||||||||||||||||||||
| Histologically� neurons are ballooned with cytoplasmic� vacuoles, which constitutes lysosome filled with gangliosides. | |||||||||||||||||||||||||||
| Positive Stains for fat (Oil Red O, Sudan Black B) | |||||||||||||||||||||||||||
| Cytoplasmic inclusions (most prominent being whorled configuration within lysosomes. Composed of onion skin layers of membranes | |||||||||||||||||||||||||||
| Progressive destruction of neurons, proliferation of microglia and accumulation of lipids in phagocytes within the CNS | |||||||||||||||||||||||||||
| Similar process in cerebellum as well as in basal ganglia, brain stem and ANS | |||||||||||||||||||||||||||
| Ganglion cells in retina are similarly swollen with GM2 gangliosides, particular at margins of macula (cherry-red-spot) appears presenting accentuation of the normal color of the macular choriod contrasted with pallor produced by swollen ganglion cells. This finding is characteristic for storage disorder affecting neurons. | |||||||||||||||||||||||||||
| Most common Tay-Sachs allele is a 4base insertion in the hexosaminidase A gene. This leads to mutation that causes a formation of a stop codon downstream | |||||||||||||||||||||||||||
| Symptoms: | |||||||||||||||||||||||||||
| Symptoms usually start at age 6months | |||||||||||||||||||||||||||
| Motor and mental deterioration(incoordination, mental obtundation, muscular flaccidy)� | |||||||||||||||||||||||||||
| Blindness | |||||||||||||||||||||||||||
| Deafness | |||||||||||||||||||||||||||
| Increased dementia | |||||||||||||||||||||||||||
| Difficulty swallowing | |||||||||||||||||||||||||||
| Muscle Atrophy, which leads to paralysis | |||||||||||||||||||||||||||
| Death usually within the first 2-3 years | |||||||||||||||||||||||||||
| Diagnosis: | |||||||||||||||||||||||||||
| Genetic Testing can be done to determine the probability of producing an offspring with that disorder | |||||||||||||||||||||||||||
| Treatment: | |||||||||||||||||||||||||||
| Unfortunately none as of now, but research is being conducting to treat patients with the disorder. | |||||||||||||||||||||||||||
| � | |||||||||||||||||||||||||||
| Personal | MedBox | ||||||||||||||||||||||||||
| Index | |||||||||||||||||||||||||||