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Enzyme Deficiencies / Lysosomal Storage Disorders
There are a number of diseases that can develop from not having enough of a particular enzyme in the body. Enzymes are substances that are needed by the body to speed up certain chemical reactions. These reactions fuel the body's everyday needs such as digesting food, creating energy to walk and run, and storing molecules in tissues and organs. When levels of certain enzymes are low or absent, also called an “enzyme deficiency,” the body may not function normally. This can cause diseases such as lysosomal storage disorders to develop.
Lysosomal storage disorders are a group of diseases where large amounts of molecules such as lipids are stored in the cells. This build up in the cells occurs since they are not able to be broken down by certain enzymes. Examples of these disorders include Gaucher disease, Fabry disease and Pompe disease.
Gaucher disease is the most common type of lipid storage disease. It is caused by a low amount of the glucocerebrosidase enzyme. This causes lipids, or fatty materials, to collect in the spleen, liver, kidneys, lungs, brain, and bone marrow. Gaucher disease affects both males and females. The three types of this disorder are:
- Type 1 (nonneuropathic) – This is the most common form of the disease. It occurs mainly in people of Ashkenazi Jewish heritage. Symptoms can appear at any age either early in life or in adulthood.
- Type 2 (acute infantile neuropathic) – This form develops during infancy. By 3 months of age a child will have an enlarged liver and spleen.
- Type 3 (chronic neuropathic) –This type is slow to develop and can begin at any time in childhood or adulthood.
Fabry disease is caused by low amounts of the enzyme alpha-galactosidase-A. This enzyme helps breakdown lipids. These molecules can build up to harmful levels in the eyes, kidneys, nervous system and heart. Males are most affected by this disorder. However a milder form is common in females.
Pompe disease is a rare disorder that is caused by a low amount of the enzyme acid alpha-glucosidase (GAA). The low amounts of GAA cause an increased amount of glycogen to build up, mainly in the heart and skeletal muscles. Glycogen is a complex carbohydrate that is a stored form of sugar used for energy. It is estimated that Pompe disease occurs in 1 in every 40,000 births.
Enzyme deficiencies can be inherited two ways, either from one or both parents:
- Autosomal recessive – Both parents do not have the disorder but they each carry and pass on the faulty gene to the child.
- X-linked recessive – The mother carries the affected gene on the X chromosome and passes it to the child.
Symptoms of Gaucher disease, Fabry disease and Pompe disease are listed below.
- Gaucher disease – Symptoms can vary depending on the type of disorder:
- Type 1: Symptoms can occur any time in life and include enlarged liver and spleen, lung, bone and kidney problems, easily bruising, and tiredness.
- Type 2: Symptoms often begin 3 months after birth and include enlarged liver and spleen, abnormal eye movement, brain damage, seizures and poor ability to suck or swallow.
- Type 3: Symptoms can begin at any time and are slow to develop. They include an enlarged spleen, liver, seizures, poor coordination, eye movement disorders, blood disorders and respiratory problems.
- Fabry disease – Burning sensations in the hands that get worse with exercise and hot weather, purple spots on the skin, decreased sweating, fever, and enlarged heart and kidneys.
- Pompe disease – Symptoms depend on the age when a person develops Pompe disease and the amount of enzyme:
- Early onset (infantile form of Pompe) – The GAA enzyme is absent or close to being absent. In the first months of life there are feeding problems, poor weight gain, muscle weakness, floppiness and head lag. Lung infections can develop because of respiratory difficulties. The heart and tongue are very enlarged in infants.
- Late onset (juvenile/adult form of Pompe) - The GAA enzyme is only partially missing. Symptoms can develop in the first stages of childhood or as an adult. The main symptom is muscle weakness.
Doctors use a variety of tools to diagnose enzyme deficiency:
- Clinical examination.
- Biopsy of the liver or other tissue.
- Genetic testing.
- Molecular analysis of cells or tissues.
- Enzyme assays that test a variety of cells or body fluids for enzyme deficiency.
Enzyme replacement therapy (ERT) is an effective treatment for people with Gaucher disease types I and III, Fabry disease and Pompe disease. ERT helps provide the body with the specific enzyme that is lacking in these diseases.
This means that for people with Gaucher disease type 1 and most type 3, ERT can decrease liver and spleen size and help reverse other symptoms. It can ease pain and improve organ function in people with Fabry disease and can decrease the heart size, help the function of the heart, and improve muscle function in people with Pompe disease.
Side effects with ERT are often related to the infusion and may include fever, headache, chills, hives, nausea, flushing, dizziness, and cough.
Sometimes side effects can disrupt a person’s life and day to day activities but it is important that a person never changes their dosage or stops taking the medication without talking to their doctor or pharmacist.
There are many resources and organizations available to help, providing support, advocacy and information:
National Gaucher Foundation
National Fabry Disease Foundation
Acid Maltase Deficiency Association (AMDA)
National Institutes of Health. NINDS. Handout on Lipid Storage Diseases Fact Sheet. NIH Publication No. 05-2628. March 2005.
National Institutes of Health. NINDS. http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm. Accessed December 28, 2011.
National Institutes of Health. NINDS. http://www.ninds.nih.gov/disorders/fabrys/fabrys.htm. Accessed December 28, 2011.
National Institutes of Health. NINDS. http://www.ninds.nih.gov/disorders/pompe/pompe.htm. Accessed December 1, 2011.