Biochemistry Answer-3

(A) Fabry disease is an X-linked disorder that
results from a deficiency in alpha-galactosidase
A. This leads to the deposition of neutral glycosphingolipids
with terminal alpha-galactosyl
moieties in most tissues and fluids. Most
affected tissues are heart, kidneys, and eyes. The
predominant glycosphingolipid accumulated is
globotriaosylceramide [galactosyl-(α1→4)-
galactosyl-(β1→4)-glucosyl-(β1→1’)-cer amide].
With increasing age, the major symptoms of the
disease are due to increase in deposition of glycosphingolipid
in the cardiovascular system.
Indeed, cardiac disease occurs in most hemizygous
males. Three types of Gaucher disease
(choice B) have been characterized and are caused
by defects in lysosomal acid beta-glucosidase
(glucocerebrosidase). Defects in this enzyme
lead to the accumulation of glucosylceramides
(glucocerebrosides), which leads, primarily, to
central nervous system (CNS) dysfunction and
also hepatosplenomegaly and skeletal lesions.
NPD (choice D) comprises three types of lipid
storage disorder, two of which (type A and B
NPD) result from a defect in acid sphingomyelinase.
Type A is a disorder that leads to
infantile mortality. Type B is variable in phenotype
and is diagnosed by the presence of
hepatosplenomegaly in childhood and progressive
pulmonary infiltration. Pathologic characteristics
of NPD are the accumulation of
histiocytic cells that result from sphingomyelin
deposition in cells of the monocyte-macrophage
system. Tay-Sachs disease (choice E) results from
a defect in hexosaminidase A leading to the
accumulation of GM2 gangliosides, particularly
in neuronal cells. This defect leads to severe
mental retardation, progressive weakness, and
hypotonia, which prevents normal motor development.
Progression of the disease is rapid and
death occurs within the second year. Krabbe
disease (choice C), also called globoid-cell
leukodystrophy, results from a deficiency in
galactosylceramidase (galactocerebroside betagalactosidase).
This disease progresses rapidly
and invariably leads to infantile mortality.

Posted in: Biochemistry Answer