Tay-Sachs Disease

Pathophysiology

1) lysosomal storage disease 2) marked by abnormal buildup of gangliosides in lysosomes 3) occurs in infantile-, juvenile-, and adult-onset forms

Signs and Symptoms

Infantile onset – 1) infants are normal at birth and develop first symptoms at 6 months, with decreasing mental alertness 2) profound mental retardation 3) growth retardation, progressive weakness, hyptonia 4) seizures 5) loss of vision 6) cherry red spot on macula Juvenile onset – 7) ataxia 8) dementia Adult onset – 9) unusual clumsiness in childhood 10) progressive motor weakness in teens 11) slow decrease in intelligence 12) psychosis 13) dysarthria 14) lower motor neuron defects

Characteristic Test Findings

Laboratory – diagnosis is by finding hexosaminidase A in the plasma or the cytoplasm of nucleated cells

Histololgy/Gross Pathology

1) ganglioside deposited in neurons of CNS 2) lipid droplets in cytoplasm 3) progressive enlargement of the brain 4) whorled membranes in cytoplasm of nerve cells

Biochemistry

defect is in a subunit of hexosaminidase A

Inheritance/Epidemiology

1) autosomal recessive 2) occurs in 1/1000 in Ashkenazi Jews 3) death is usually by 3 years of age with infantile onset and early teens with juvenile onset 4) defect is on chromosome 15q 5) 1/30 Ashkenazi Jews carries the gene

Tips for USMLE

1) cherry red spot on macula is also found in Niemann-Pick disease, Sandhoff’s disease, mucolipidosis type 1, and central artery retinal occlusion 2) defect is in hexosaminidase A