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Lysosomal Storage Diseases

Lysosomal Storage Diseases



Overview

Lysosomal storage diseases or disorders (LSDs) are rare genetic conditions that cause a buildup of toxic materials in your body’s cells. People with LSDs lack certain enzymes or a substance that helps the enzyme work (enzyme activator or modifier). Without functioning enzymes, your body can’t break down fats and sugars and other substances. If those build up in your body, they can be harmful.

Lysosomal storage diseases usually appear during pregnancy or soon after birth. More rarely, adults may develop LSDs. People usually have more severe cases when an LSD starts early and more mild cases when an LSD starts later.

There are no cures for lysosomal storage diseases. But treatments can help you to manage your symptoms and lessen damage to organs and tissues.

How do enzymes and lysosomes work?

Enzymes assist your cells’ lysosomes with metabolism. They cause chemical reactions to help the lysosomes break down:

Carbohydrates (fiber, starches and sugars).

Lipids (fats).

Proteins.

Older cells.

If these substances build up in your cells, they become toxic. The build-up causes damage to other cells and organs. The damage from lysosomal storage disorders can affect many parts of your body, including your:

Brain.

Central nervous system.

Heart.

Skeletal system.

Skin.

What are the types of lysosomal storage disease?

Researchers have found more than 50 lysosomal storage diseases. And they continue to identify more.

Generally, there are three main types of LSDs based on which enzyme is lacking:

Lipidoses

This type occurs when your body lacks an enzyme to break down fats. Specific conditions include:

Cholesteryl ester storage disease.

Wolman disease.

Mucopolysaccharidoses

These happen when your body lacks an enzyme to break down complex sugar molecules (glycosaminoglycans). Specific conditions include:

Hunter syndrome.

Hurler’s disease.

Sphingolipidoses

This type comes from not having enough of an enzyme to break down fatty substances (sphingolipids). They’re responsible for specific jobs in your cells, including protecting the surface of your cells. Specific conditions include:

Fabry disease.

Gaucher disease.

Krabbe disease (globoid cell leukodystrophy).

Metachromatic leukodystrophy.

Niemann-Pick disease (NP).

Sandhoff disease.

Tay-Sachs disease.

Other types of LSDs

Batten disease.

Cystinosis.

Danon disease.

Pompe disease.

Symptoms

Symptoms of lysosomal storage disease vary based on the:

Cells or organs impacted by the LSD.

Type of LSD.

Symptoms commonly found in many types of lysosomal storage disorders include:

Abnormally large organs in your abdomen (visceromegaly) like your kidneys, liver, pancreas, spleen or stomach.

Changes to your skeletal muscle.

Coarse facial features like a bulging forehead, flat nose and large lips.

Developmental delay that worsens over time.

Causes

Lysosomal storage diseases are inherited metabolic disorders. Most LSDs are autosomal recessive disorders. You must inherit a changed (mutated) gene from each parent for you to develop an LSD. Your parents carry these gene mutations, but they don’t have a lysosomal storage disease.

When both of your parents have a mutated gene, you have a:

1 in 4 chance of not having the mutated gene (no risk of an LSD).

1 in 4 chance of developing an LSD.

1 in 2 chance of being a carrier who doesn’t develop an LSD.

In some conditions, only one parent may carry this gene mutation (X-linked inheritance). Three LSDs have X-linked inheritance:

Danon disease.

Fabry disease.

Hunter syndrome.

Lysosomal storage diseases may also get triggered by:

Inflammation.

The interaction between the byproducts of metabolism (free radicals) and your body (oxidative stress).

Diagnosis

Your healthcare provider can diagnose lysosomal storage diseases during pregnancy. They may use prenatal screening tests including:

Amniocentesis.

Chorionic villus sampling.

Your provider can screen newborns for LSDs with blood tests to look for the missing enzyme. They may use dried blood spots, where they collect blood with a finger prick. Your provider then blots these small blood spots on absorbent paper. Once the spots dry, they test the spots for enzymes.

If your provider suspects an LSD, they may refer you or your child to a provider who specializes in the endocrine system (endocrinologist or pediatric endocrinologist). In children and adults, your provider may suggest tests including:

Blood tests, to check enzyme levels.

Genetic testing, to look for changes (mutations) in your genes.

Punch biopsy, to test for genetic mutations.

Urine tests (urinalysis), to measure levels of substances that enzymes normally act upon (substrates).

Your provider may suggest other tests to check for damage to your organs. These tests may include:

Complete blood count.

Eye exam.

Hearing test.

Heart tests, such as echocardiogram and electrocardiogram (EKG).

Kidney function tests.

Liver function tests.

MRI.

X-ray.

Treatment

Providers usually treat lysosomal storage disorders in specialized medical centers. Treatments for LSDs include:

Enzyme replacement therapy (ERT): Your provider inserts a genetically engineered enzyme into your vein (intravenously).

Stem cell transplants: Your provider transplants stem cells from donors or umbilical cord blood to help produce the missing enzyme. Stem cell transplants can also reduce inflammation and tissue damage.

Substrate reduction therapy (SRT): You take medications that reduce the substances that build up in your cells. For instance, you can take miglustat to treat Gaucher disease. Other SRTs are currently in clinical trials.

Researchers continue to test new LSD treatments such as:

Gene therapy: Experimental gene therapy replaces damaged genes with healthy genes.

Pharmacological chaperone therapy (PCT): Small molecules bind to damaged enzymes and improve how the lysosomes work.

Other LSD treatments help manage symptoms of the disease. These treatments may include:

Immunosuppressants.

Nonsteroidal anti-inflammatory drugs (NSAIDs).

Orthopedic braces.

Other medications, based on symptoms and organs affected.

Physical therapy.

Speech therapy.

Surgery.

Type of Doctor Department : A Metabolic Specialist/Biochemical Geneticist ,  Neurologists, Cardiologists, Orthopedists, Ophthalmologists, and Genetic Counselors


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