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2.6.2 Fabry’s Disease
The second most frequently occurring lysosomal storage disease is Fabry disease
with an occurrence of one in 117,000 births characterized by deficiency of
α-galactosidase A (α-gal A). This results in accumulation of globotriaosylceramide
(Gb3) in lysosomes. Though it is an X-linked disease and affects mostly hemizygous men, heterozygous women may suffer the same level of severity and decline
in lifespan (Mehta et al. 2010). Fabry’s disease often affects renal cells, endothelial
cells and neuronal cells. Clinical manifestations include renal dysfunction and cardiac problems such as ischaemia, gastrointestinal problems, etc. Enzyme replacement therapy (ERT) for Fabry’s disease was introduced in 2001. Fabry’s disease is
a progressive disorder and enzyme replacement therapy at initial stages was found
to be very helpful in disease control. Agalsidase alfa (Replagal
®
) and agalsidase
beta (Fabrazyme
®
) are two recombinant α-galactosidase enzymes available for
ERT. Agalsidase alfa is isolated from cultured human skin fibroblasts whereas agalsidase beta is isolated from Chinese hamster ovary cells. ERT certainly improved
quality of life by decreasing organ damage and reducing or even reversing disease
progression (Fig. 2.11).
2.6.3 Glycogen Storage Disease Type II (Pompe disease)
Pompe disease is a lysosomal storage disease due to the lack of the enzyme
α-glucosidase (GAA). This leads to lysosomal accumulation of glycogen, mostly in
cardiac and skeletal muscles. It is also known as glycogen storage disease Type II
(GSDII) or acid malatase deficiency. Pompe disease is categorized into two forms,
viz. infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD).
In infantile-onset Pompe disease (IOPD) symptoms start within 2 months after birth
often with cardiomyopathy, and death occurs before the age of 1 year if it remains
untreated. In late-onset Pompe disease (LOPD) symptoms appear in the later stages
of life ranging from greater than 1 year to adulthood. LOPD progress slowly and
eventually leads to respiratory failure. Pompe disease is currently managed by
Fig. 2.10 Crystal structure
of velaglucerase alfa chain
A (pdb id: 2WKL)
S.S. Kumar and S. Abdulhameed
2.6.2 Fabry’s Disease
The second most frequently occurring lysosomal storage disease is Fabry disease
with an occurrence of one in 117,000 births characterized by deficiency of
α-galactosidase A (α-gal A). This results in accumulation of globotriaosylceramide
(Gb3) in lysosomes. Though it is an X-linked disease and affects mostly hemizygous men, heterozygous women may suffer the same level of severity and decline
in lifespan (Mehta et al. 2010). Fabry’s disease often affects renal cells, endothelial
cells and neuronal cells. Clinical manifestations include renal dysfunction and cardiac problems such as ischaemia, gastrointestinal problems, etc. Enzyme replacement therapy (ERT) for Fabry’s disease was introduced in 2001. Fabry’s disease is
a progressive disorder and enzyme replacement therapy at initial stages was found
to be very helpful in disease control. Agalsidase alfa (Replagal
®
) and agalsidase
beta (Fabrazyme
®
) are two recombinant α-galactosidase enzymes available for
ERT. Agalsidase alfa is isolated from cultured human skin fibroblasts whereas agalsidase beta is isolated from Chinese hamster ovary cells. ERT certainly improved
quality of life by decreasing organ damage and reducing or even reversing disease
progression (Fig. 2.11).
2.6.3 Glycogen Storage Disease Type II (Pompe disease)
Pompe disease is a lysosomal storage disease due to the lack of the enzyme
α-glucosidase (GAA). This leads to lysosomal accumulation of glycogen, mostly in
cardiac and skeletal muscles. It is also known as glycogen storage disease Type II
(GSDII) or acid malatase deficiency. Pompe disease is categorized into two forms,
viz. infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD).
In infantile-onset Pompe disease (IOPD) symptoms start within 2 months after birth
often with cardiomyopathy, and death occurs before the age of 1 year if it remains
untreated. In late-onset Pompe disease (LOPD) symptoms appear in the later stages
of life ranging from greater than 1 year to adulthood. LOPD progress slowly and
eventually leads to respiratory failure. Pompe disease is currently managed by
Fig. 2.10 Crystal structure
of velaglucerase alfa chain
A (pdb id: 2WKL)
S.S. Kumar and S. Abdulhameed