(PDF) Lysosomal Storage Diseases

1. In general, explain the nature and pathology of Lysosomal Storage Diseases.?
Answer:
Mainly lysosomal storage disease is caused by abnormal build up of various toxic material in our
body cells that results in the deficiency of enzymes. This disease affect our skeleton, brain, skin,
heart and central nervous system. The main function of lysosme is the breakdown of compels
substances into simple ones when this process does not takes place then the substrate begins to
accumulate in the cells that’s why this disease is called “storage disorder” There are nearly 50
types of this disorder so we can say that it’s signs and symptoms vary from disease to disease.
Clinical trials are in progress to identify more types of this disease. They are struggling and there
is no complete treatment has been approved so far.
Reference: https://rarediseases.org/rare-diseases/lysosomal-storage-disorders/
2. How many hydrolases have been conjectured to the possibility of causing a Lysosomal
Storage Disease?
Answer:
The hydrolases conjected to the possibility of causing a lysosomal storage disease is more
than 60. Lysosomal hydrolases are mainly glycoproteins act as acidic PH so they are
synthesized in rough endoplasmic reticulum. Lysosomal hydrolases includes proteases,
lipases, nucleases, glucosidases, phosphatases and sulfatases. They provides nucleic acid,
amino acids, fatty acids and sugars for neutralization in cellular synthesis. There are twelve
mechanisms lead to deficient acid hydrolases activity and abnormal storage of substrate
have been recognized.
Reference: https://www.sciencedirect.com/topics/medicine-and-dentistry/lysosomal-storage-
disease#:~:text=To%20date%2C%2058%20genetically%20determined,of%20intracellular%20a
nd%20extracellular%20macromolecules.

3. What are three classes of proteins that could lead to LSDs? List 2 defective proteins in
each class.
Lysosomal membrane proteins are classified in to several different groups of small metabolites
exporter proteins including
1. Enzyme protecting protein
This type of protein causes galactosialidosis. It is caused by a mutation in the CTSA gene which
leads to a deficiency of enzymes β-galactosidase and neuraminidase. By this lysosomes of cells
inhibit from functioning. Due to this accumulation of toxic matter occur within the cell. Two defect
proteins
Cathepsin A. Its example is Galactosialidosis
2. Soluble nonenzymetic proteins
Niemann–Pick type C (NPC) This associated with mutations
in NPC1 and NPC2 genes. This disease causes the enlargement of liver and spleen.
This responsible for disability and premature death in all cases beyond early childhood.
Two defective protein
GM2-AP
NPC2
3. Transmemrane proteins
Salla disease (SD)
It is an autosomal recessive disease. It is one of 40 Finnish heritage diseases and affects
approximately 130 individuals, mainly from Finland and Sweden. This disease reduced muscle
tone and strength.
Two defective proteins
NPC1
Sialin
Reference
https://en.wikipedia.org/wiki/Lysosomal_storage_disease