Lysosomal storage disorders

Lysosomal storage diseases are a group of over 50 rare diseases. They affect the lysosome, the structure in your cells that breaks down substances such as proteins, carbohydrates, and old cell parts so that the body can recycle them.

People with these disorders lack important enzymes (proteins that speed up reactions in the body). Without these enzymes, the lysosome is unable to break down these substances.

When this happens, they accumulate in cells and become toxic. They can damage cells and organs in the body.

Types of lysosomal storage diseases

Each disorder affects a different enzyme and has its own set of symptoms. They understand:

Fabry disease: It affects your ability to produce alpha-galactosidase A. This enzyme breaks down a fatty substance called globotriaosylceramide. Without the enzyme, this fat accumulates in cells and damages them.

Symptoms may include:

Pain, numbness, tingling, or burning in the hands and feet
Body aches
Fever
Tiredness
Red or purple skin sores
Trouble sweating
Swelling in the lower legs, ankles, and feet
Clouding of the cornea (the clear cover on the front of the eye)
Diarrhea, constipation, or both
Trouble breathing
Ringing in the ears and hearing loss
Dizziness
Abnormal heart rhythms, heart attack, and stroke

Gaucher disease: This disease is caused by a deficiency of glucocerebrosidase (GBA). This enzyme breaks down a fat called glucocerebroside. Without GBA, fat accumulates in the spleen, liver, and bone marrow.

There are three types of Gaucher disease, each with different symptoms. In general, symptoms include:

Anemia (low red blood cell count)
Enlarged spleen and liver
Easy bleeding and bruising
Tiredness
Bone pain and fractures
Joint pain
Eye problems
Seizures

Krabbe disease: affects the nervous system. A lack of the enzyme galactosylceramidase causes this condition. This enzyme helps build and maintain myelin, the protective covering around nerve cells that helps nerves communicate with each other.

Symptoms appear within the first few months of life and include:

Muscle weakness
Stiff limbs
Trouble walking
Vision and hearing loss
Muscle spasms
Seizures

Metachromatic leukodystrophy: You can get metachromatic leukodystrophy if you don't have the enzyme arylsulfatase A. It usually breaks down a group of fats called sulfatides. Without the enzyme, these fats accumulate in the white matter, the part of the brain that contains nerve fibers. They destroy the myelin sheath that surrounds and protects nerve cells.

Metachromatic leukodystrophy comes in many forms. Symptoms may include:

Loss of feeling in the hands and feet
Seizures
Trouble walking and talking
Vision and hearing loss

Mucopolysaccharidosis: This is a group of diseases that affect the enzymes that break down certain carbohydrates. Continuous carbohydrates accumulate in many different organs.

Symptoms of mucopolysaccharidosis affect many parts of the body and may include:

Short height
Stiff joints
Trouble speaking and hearing
Ongoing runny nose
Learning problems
Heart issues
Joint problems
Trouble breathing
Depression

Niemann-Pick disease: this is a group of diseases. The most common types are A, B and C.

In types A and B, people lack an enzyme called acid sphingomyelinase. It breaks down a fatty substance called sphingomyelin, which is found in every cell.
In type C, the body cannot break down cholesterol and fats in the cells. Cholesterol is stored in the liver and spleen. Other fats accumulate in the brain.

Niemann-Pick symptoms include:

An enlarged liver and spleen
Trouble moving your eyes up and down
Jaundice (yellow skin and eyes)
Slow development
Breathing problems
Heart disease

Pump disease: affects the alpha-glucosidase enzyme. This enzyme breaks down the sugar glycogen into glucose. Without alpha-glucosidase, glycogen accumulates in muscle and other cells.

Symptoms include:

Severe muscle weakness
Poor muscle tone
Lack of growth and weight gain in infants
An enlarged heart, liver, or tongue

Tay-Sachs disease: caused by a deficiency of the enzyme hexosaminidase A (Hex-A). This enzyme breaks down a fatty substance called GM2 ganglioside in brain cells. Without it, fat accumulates in nerve cells and damages them.

Children with Tay-Sachs disease grow normally during the first few months of life. Then their development slows down. They lose control of their muscles. It becomes more difficult for them to sit, crawl and walk. Other symptoms include:

A red spot in the back of the eye
Vision and hearing loss
Seizures

How do these disorders occur?

Most lysosomal storage diseases are passed on from parents to children. Usually, a child must inherit the defective gene from both parents. If a child receives the gene from only one parent, they will be a carrier and will not show any symptoms.

Faulty genes affect how your body produces enzymes that break down substances in cells.

Lysosomal storage diseases are rare, but some forms are more common in certain groups of people. For example, Gaucher disease and Tay-Sachs disease are more common in people of European Jewish descent.

Symptoms

Symptoms depend on the missing enzyme.

Each of these conditions has different symptoms depending on the cells and organs it affects.

Diagnostics

Your doctor may test your baby for these conditions during pregnancy. If your child has symptoms, blood tests may reveal the missing enzyme.

The doctor may also do the following tests:

Magnetic resonance imaging uses strong magnets and radio waves to produce images of the brain.
During a biopsy, a small piece of tissue is taken and examined under a microscope for signs of disease.

Early detection of these diseases is important. Treatment can slow down lysosomal storage diseases and improve your child's prognosis.

Treatment

Although there is no cure for lysosomal storage diseases, some treatments can help.

Enzyme replacement therapy delivers the missing enzyme through a vein (IV).
Substrate recovery therapy reduces the amount of substance that accumulates in cells. For example, the drug miglustat (Zaveska) treats a form of Gaucher disease.
Stem cell transplant uses donor cells to help the body produce the enzyme it needs.

Treatment for the symptoms of the disease includes: