Lysosomal Storage Disease

Introduction

Lysosome is an important membrane-bound cell organelle that is present in the eukaryotic cell of animals. The area that is present between the membrane is called the lumen. The lumen is acidic in nature due to its pH level which lies between 4.5 to 6. It contains digestive enzymes that help in the breakdown of proteins, nucleic acids, carbohydrates, and lipids. In addition to this, lysosomes are engaged in various processes of cells like metabolism of energy, waste discharge, cell signaling, cell membrane repair, etc. The lysosome is also known as the suicide bag of the cell.

Lysosomal Diseases

Lysosomal storage diseases are genetic metabolic diseases. Due to the deficiencies of enzymes, various toxic materials are accumulated in the body cells leading to lysosomal storage disorders. Lysosomal storage diseases consists of more than 50 rare diseases that acts on different parts of the body. That includes the central nervous system, skeleton, heart, skin, etc. The individual with this disorder is devoid of important enzymes. As a result, the lysosome fails to break down the biological polymers. The build-up cells become toxic and further, they can spoil cells, tissues, or organs that are present in the body.

Types of Disorders

Deficiency of different types of enzymes leads to different lysosomal storage disorders. Various types of the disorder have been described below −

Fabry disease

These diseases prevent the production of alpha-galactosidase A. The enzyme alpha-galactosidase A helps in the breakdown of fat. If the enzymes are not produced in the lysosome it leads to the deposition of fats in cells and spoils them. The general symptoms include

• Numbness, prickling, pain, and sensation of burning in feet and hands.

• Pain in the body

• Temperature

• Tiredness

• The appearance of skin lesions that becomes purple or red in colour.

• Inflammation of the ankles, legs, and feet.

• Cornea is affected.

• Diarrhea and constipation.

• Light-headedness.

• Loss of hearing.

• Irregular heartbeat, stroke, and heart attack.

Gaucher disease

The lack of enzyme glucocerebrosidase causes Gaucher disease. The absence of this enzyme leads to the deposition of fats, liver, and bone marrow. Gaucher disease is further subdivided into three types, each with different symptoms. General symptoms include −

• Anemia

• Spleen and liver enlargement

• Frequent bleeding and bruising

• Fatigue

• Pain in bones and brittle bones

• Joint pain

• Eye problems.

Krabbe Disease

The absence of enzyme galactosylceramidase causes Krabbe disease. This type of enzyme helps in maintaining and production of myelin. Krabbe disease affects the nervous system and can be seen during the first few months of life with symptoms including −

• Weakness in the muscles

• Stiff limbs

• Difficulties in walking

• Muscle cramps

• Seizures.

Metachromatic leukodystrophy (MLD)

This disease occurs in our body due to the absence of the enzyme arylsulfatase A. This enzyme breaks down the cluster of fats known as sulfatides. These fats constitute white matter in the parts of the brain (contains nerve cells). Without the enzyme arylsulfatase A, the white matter damages the myelin coating. The general symptoms include −

• Loss of sensation in feet and hands

• Difficulties in taking and walking

• Loss of hearing and vision

• Seizures

Mucopolysaccharidosis (MPS)

This condition occurs due to the absence of a few lysosomal enzymes or enzymes with a lack of functionality in the cells. These enzymes break down the long-chain sugar carbohydrates into simpler molecules for further processes. And the carbohydrates get deposited in the cells if not processed leading to various disorders. The common symptoms include

• Stiff joints

• Dwarfism

• Difficulties in speaking and hearing

• Constant running nose

• Learning difficulties

• Heart problems

• Breathing difficulties

• Depression

Niemann Pick disease

This is a group of disorders. Type A, B, and C are the most common forms of this disorder. The enzyme acid sphingomyelinase is absent in types A and B. This enzyme breaks down the fatty acid sphingomyelin that is available in each cell. In type C, a failure of transport system leads to accumulation of cholesterol and glycolipids in lysosomes resulting in enzyme deficiency. The symptoms include −

• Enlargement of liver and spleen

• Difficulties in eye movement

• Slow development

• Jaundice

• Heart disease

• Breathing problems

Pompe diseases

This is due the deficiency of enzyme alpha-glucosidase. This enzyme helps in the breakdown of glycogen into glucose. The general symptoms include −

• Muscle weakness

• Poor muscle tone

• Retarded growth

• Lack of weight gain

• Enlargement of heart, tongue, and liver

Tay-Sachs Disease

This disease is due to the lack of enzyme hexosaminidases A. This enzyme helps in the breakdown of fatty cells in brain cells. The absence of this enzyme causes the deposition of fat in the brain cells. In the initial few months of life, growth and development appear normal in babies. But later, the development becomes slow making it difficult for them to crawl, walk and sit. Other symptoms include a red spot in the black portion of the eye, loss of vision and hearing, and seizures.

Cause of Lysosomal Storage Disease

Lysosomal storage diseases are inherited metabolic diseases. Due to the deficiencies of various enzymes, toxic materials accumulate in the body cells leading to lysosomal storage disorders.

Lysosome as the Therapeutic Target

Lysosome is an important membrane-bound cell organelle that is present in the eukaryotic cells of animals. Lysosomes are engaged in various processes of cells like metabolism of energy, degrading and recycling cellular waste, cell signaling, cell membrane repair, etc. A lysosome is also known as the suicide bag of the cell. Obstruction in genes encoding lysosomal proteins causes lysosomal storage disorders. In this case, enzyme replacement therapy proved to be helpful.

Conclusion

Membrane-bound cell organelles that contain enzymes that help in digestion are known as lysosomes. Lysosomal storage diseases are the class of more than 50 rare diseases that acts on different parts of the body.

FAQs

Q1. Why lysosome is known as a suicide bag?

Ans. Lysosome cell organelles contain enzymes that help in digestion. The digestive enzyme starts eating its own cell in case of lysosomes burst open. So lysosomes are considered suicide bags.

Q2. What is a heart attack?

Ans. When enough blood does not reach your heart it leads to a heart attack. It is mainly due to artery blockage. A heart attack can be fatal.

Q3. What are the symptoms of diarrhea?

Ans. Diarrhea is caused by the virus. The symptoms include pain or cramp in the abdomen, vomiting, fever, urgent blood movement, and stool accompanied by blood or mucus.

Q4. What is a cornea?

Ans. It is the outer layer present in front of the eyes. It is the protective structure of the eyes and helps in focusing light on the retina.

Q5. What is the main cause of anemia?

Ans. Anemia is caused due to deficiencies of iron. Iron is required for the body to make hemoglobin. Iron supplement medicines are prescribed by the doctors to treat anemia.