CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 28: TAY-SACHS D ISE A SE
A Jewish couple of Eastern European descent presents for prenatal
counseling after having a child die with a progressive neurologic disorder with
loss of motor skills and abnormally large head and an abnormal eye examina-
tion. An autopsy shows Tay-Sachs disease.
Inheritance: Autosomal recessive; 1:30 carrier rate in Ashkenazi Jews.
Molecular basis of disorder: Lysosomal storage disorder with
deficiency of hexosaminidase A enzyme resulting in GM2 gangliosides
accumulating throughout the body.
C L IN IC A L C O R R E L A T IO N
Tay-Sachs disease is a fatal genetic disorder where harmful amounts of lipids
called ganglioside GM2 accumulate in the nerve cells and brains of those
affected. Infants with this disorder appear normal for the first several months
of life, and then as the lipids distend the nerve cells and brain cells, progres-
sive deterioration occurs; the child becomes blind, deaf, and eventually unable
to swallow. Tay-Sachs disease occurs mainly in Jewish children of Eastern
European descent, and death from bronchopneumonia usually occurs by age 3
to 4 years. A reddish spot on the retina also develops, and symptoms first
appear around 6 months of age. It is a lysosomal storage disorder with insuf-
ficient activity of the enzyme hexosaminidase A, which catalyzes the
biodegradation of the gangliosides. The diagnosis is made by the clinical sus-
picion and serum hexosaminidase level. Currently there is no treatment avail-
able for this disease.
A PPR O A C H TO L Y SO SO M A L ST O R A G E
Be familiar with the lysosomal storage disorders.
Know about the synthesis and degradation of sphingolipids.
Ceramide: A component of all sphingolipids that is composed of a long-
chain fatty acyl group in an amide linkage to sphingosine.
Ganglioside: Complex carbohydrate-rich glycosphingolipids containing
three or more monosaccharides esterified to ceramide with at least one
of the sugars being A-acetylneuraminic acid (sialic acid). Gangliosides
are membrane components found on nerve endings.