Lysosomal Storage Disorders - An Overview

Introduction

Rare genetic disorders are genetic conditions that are not commonly seen. Conditions that are caused by changes in the genetic makeup of an individual are called genetic disorders. Some conditions are passed from parents to their children, and there are multiple people with that condition. However, some conditions are not always passed on to the children and may stay hidden. The children might carry a defective gene but might not have the disorder expressed. Some conditions are expressed for the first time in some people without a family history. A rare genetic disorder can be complex and often become serious. They can sometimes worsen as the child grows.

What Are Lysosomal Storage Disorders?

Lysosomal storage disorders are conditions in which an accumulation of toxic substances occurs in the cells of the body. People who have this condition lack an enzyme (a type of protein that fastens some reactions) or a substance that activates the enzyme to function properly. When an enzyme does not function properly, the body might find it difficult to digest fats, sugars, and other substances. As a result, they accumulate in the body and cause toxic effects.

What Are the Functions of Enzymes and Lysosomes?

A lysosome is an organelle that is membrane-bound and contains enzymes. They play an important role in the various functions of the cell. They break down the parts of the cell that are worn out or in excess. The enzymes in the lysosome can help to invade viruses and other foreign bodies that enter the body. They also help with the metabolism of the body. The lysosomes help to break down carbohydrates, lipids, proteins, and other cells that are old. These materials can become toxic if not broken down properly, causing them to accumulate in the body. The accumulation of these substances can be dangerous to the body. It can affect other cells and organs. The lysosomal storage disorder can also affect organs like brain, central nervous system, heart, skeletal system, and skin.

What Are the Types of Lysosomal Storage Disorders?

Studies have helped in the discovery of more than 50 types of lysosomal storage disorders, and many are still on the go. Broadly, lysosomal storage disorders are classified into three categories on the basis of the defective enzyme. They can include:

1. Lipidoses: This occurs when the body is not able to break down fats. The common conditions of having this disorder can include cholesteryl ester storage disease (a liver condition caused by deficiency of lysosomal acid lipase enzyme) and Wolman disease (a rare genetic disorder characterized by the total absence of an enzyme called lysosomal acid lipase).

2. Mucopolysaccharidoses: This is characterized by the deficiency of an enzyme to digest glycosaminoglycans. Glycosaminoglycans are complex sugar molecules. The conditions having this can include Hunter syndrome (a genetic condition caused by the deficiency of an enzyme called iduronate 2-sulfatase enzyme) and Hurler’s disease (a condition that occurs due to the lack of an enzyme that helps to digest sugar).

3. Sphingolipidoses: In this disorder, the body lacks an enzyme that helps to digest sphingolipids. Sphingolipids are the fatty substances in the body. They help in protecting the surface of the cells. Examples of this type of disorder can include Fabry disease (a rare X-linked lysosomal disorder that causes excessive deposition of lipids) and Gaucher disease (a rare genetic disorder where the body lacks an enzyme called glucocerebrosidase).

What Are the Symptoms of Lysosomal Storage Disorders?

The lysosomal storage disorder can vary depending on the organs or cells affected and the type of disease. The common symptoms can include:

• Visceromegaly (an abnormal enlargement of the organs in the abdomen like kidneys, liver, pancreas, spleen, or stomach).

• Skeletal muscle changes.

• Facial features like a bulging forehead, flat nose, and large lips.

• Developmental delay (it might worsen with time).

• Dehydration.

• Acidosis (a build-up of acid in the body fluids).

• Vomiting.

• Stunted growth in children.

• Pain and numbness in hands and feet.

• Breathing difficulties.

How Are Lysosomal Storage Disorders Diagnosed?

Lysosomal storage disorders are diagnosed during pregnancy itself in most cases. This can be done by:

• Amniocentesis: It is a test done to check genetic disorders during the prenatal period. A small amount of amniotic fluid is extracted to do the laboratory test.

• Chorionic Villus Sampling: It is a prenatal test done to check any genetic defects in the baby. In this test, a sample is taken from the placenta (an organ that helps in providing nourishment to the growing fetus). It is considered to be very accurate.

Newborns are also tested for these conditions. The tests done on newborns can include:

• Dried Blood Spots: A finger prick on the newborn is used to collect blood from the newborn. It is collected as small blood spots on an adsorbent paper. These are tested for the enzymes once dry.

Healthcare professionals might advise screening tests in children who are suspected of having lysosomal storage disorders. They might be referred to a pediatric endocrinologist, a doctor who takes care of hormones and other chemical substances in children. They might advise parents to do the following tests:

• Blood Tests: These are done to check the levels of various enzymes in the body.

• Genetic Tests: These are done to check for mutations in the child’s genetic makeup.

• Punch Biopsy: It is also done to test for checking genetic mutations.

• Urinalysis: It is used to test the levels of various substances that the enzyme usually acts on. Urine glycosaminoglycan is the most commonly done urine test.

Other tests like complete blood count (CBC), eye exams, hearing tests, kidney and liver function tests, echocardiogram, and electrocardiogram might be advised depending on the symptoms presented.

How Are Lysosomal Storage Disorders Treated?

Treatments for the condition include:

• Enzyme Replacement Therapy (ERT): A genetically modified enzyme is injected into the veins.

• Stem Cell Transplantation: In this, the stem cells from donors that have the ability to produce the enzymes are transplanted. This can also help to reduce inflammation and tissue damage.

• Substrate Reduction Therapy (SRT): Medication that helps to reduce the accumulation of toxic substances in the body is given. More medicines are under research.

Other treatment approaches that are under research include gene therapy, pharmacological chaperone therapy (PCT), etc.

Conclusion

The condition currently can not be prevented from being inherited. However, appropriate treatments can help to improve the quality of life. Psychologists and counselors can help the patient to be emotionally and mentally stable to face this condition. Continuous monitoring helps to prevent the condition from becoming worse. Healthcare professionals can suggest other treatment options that might improve the symptoms.