75
Genetics
Lysosomal storage disorders consist of more than 70 genetic disease that are monogenic (controlled by 1 gene) in nature. They can be inherited as autosomal recessive
disorders. Only 3 of them inherited as X linked diseases [27]. LSDs are caused
when genetic mutation is occurred in those genes that codes for lysosomal proteins
like proteases, activators, transporters and lipases, etc. These mutations can defect
the functioning of lysosomes that results in accumulation of wastes and toxins in the
cell and ultimately cause cell death [28].
Treatment
There are some therapeutic measures that can be used for the treatment of lysosomal
storage disease. The mutated enzyme can be treated by enzyme replacement therapy
(ERT), while the accumulation of substrates in the lysosomes can be decreased by
using substrate-reduction therapy [29]. Chaperone therapy is used to increase the
functioning of mutated enzyme. Other treatments like gene therapy can also be used
for their treatment but there are many LSDs that cannot be fully cured by these
therapies [30]. Some of the recommended FDA approved drugs are given in
Table 4.4.
Disorders of Purine and Pyrimidine Metabolism
Lesch–Nyhan Syndrome
Lesch–Nyhan disease is a rare X-linked recessive disorder of purine metabolism
caused by the defect in hypoxanthine guanine phosphoribosyl-transferase (HGPRT)
enzyme which is used in salvage pathway as shown in Fig. 4.2. In 1964, this disease
was first described by W. Nyhan and M. Lesch who observed unusual symptoms in
Table 4.4 FDA of approved drugs for the treatment of selected Lysosomal storage disease
isorder
Approved drug
Production site
Therapy type
References
Gaucher
disease
• Imigluceras
• Velaglucerase alfa
• Taliglucerase alfa
• Secreted from chinese
hamster ovary (CHO) cells
• Produced in Human cells
• Produced in plant cells
• Recombinant
enzyme
[29]
Fabry
disease
• Agalsidase beta
• Agalsidase alfa
• Produced in CHO cells
• Produced in human cells
• Recombinant
enzyme
• Chaperone
therapy
Pompe
disease
• Alglucosidase alfa • Produced in CHO cells
• Recombinant
enzyme
4 Inherited Metabolic Disorders: A Current Status
Genetics
Lysosomal storage disorders consist of more than 70 genetic disease that are monogenic (controlled by 1 gene) in nature. They can be inherited as autosomal recessive
disorders. Only 3 of them inherited as X linked diseases [27]. LSDs are caused
when genetic mutation is occurred in those genes that codes for lysosomal proteins
like proteases, activators, transporters and lipases, etc. These mutations can defect
the functioning of lysosomes that results in accumulation of wastes and toxins in the
cell and ultimately cause cell death [28].
Treatment
There are some therapeutic measures that can be used for the treatment of lysosomal
storage disease. The mutated enzyme can be treated by enzyme replacement therapy
(ERT), while the accumulation of substrates in the lysosomes can be decreased by
using substrate-reduction therapy [29]. Chaperone therapy is used to increase the
functioning of mutated enzyme. Other treatments like gene therapy can also be used
for their treatment but there are many LSDs that cannot be fully cured by these
therapies [30]. Some of the recommended FDA approved drugs are given in
Table 4.4.
Disorders of Purine and Pyrimidine Metabolism
Lesch–Nyhan Syndrome
Lesch–Nyhan disease is a rare X-linked recessive disorder of purine metabolism
caused by the defect in hypoxanthine guanine phosphoribosyl-transferase (HGPRT)
enzyme which is used in salvage pathway as shown in Fig. 4.2. In 1964, this disease
was first described by W. Nyhan and M. Lesch who observed unusual symptoms in
Table 4.4 FDA of approved drugs for the treatment of selected Lysosomal storage disease
isorder
Approved drug
Production site
Therapy type
References
Gaucher
disease
• Imigluceras
• Velaglucerase alfa
• Taliglucerase alfa
• Secreted from chinese
hamster ovary (CHO) cells
• Produced in Human cells
• Produced in plant cells
• Recombinant
enzyme
[29]
Fabry
disease
• Agalsidase beta
• Agalsidase alfa
• Produced in CHO cells
• Produced in human cells
• Recombinant
enzyme
• Chaperone
therapy
Pompe
disease
• Alglucosidase alfa • Produced in CHO cells
• Recombinant
enzyme
4 Inherited Metabolic Disorders: A Current Status