Lysosomal storage disease

Lysosomes are organelles that contain enzymes which metabolize (break down) excess sugars and lipids into substances that the body can use. Inherited deficiencies of any lysosomal components, including lysosomal enzymes, are referred to as lysosomal storage disorders or lysosomal storage disease.

Definition & Facts

Lysosomal storage disorders are health condition that results in the accumulation of undigested or partially digested sugars and lipids (fats) in different parts of the body. The buildup of these substances ultimately causes damage to body cells and organs and can lead to death.

There are over 50 lysosomal storage disorder types. The age of onset and clinical manifestations differ significantly among patients with different types of these disorders, and there is a remarkable phenotypic heterogeneity between family members with identical mutations. The diseases are classified by the particular enzymes involved. Some of these diseases include:

• Pompe disease affects the liver, heart, and muscles
• Gaucher disease affects the spleen and bones.
• Hurler syndrome causes intellectuality disability, anemia, valvular heart disease, deafness; has an impact on the eyes, spleen, joints, and liver
• Tay-Sachs disease mainly affects the brain and nervous system
• Morquio syndrome affects the bones and joints
• Fabry disease causes skin problems, heart problems, and hearing problems
• Maroteaux-Lamy syndrome- can cause macrocephaly (an abnormally large head), hydrocephalus, and macroglossia (an enlarged tongue). Upper respiratory infections and cloudiness of the cornea may also occur.

Symptoms & Complaints

• Seizures
• Difficulty breathing
• Anemia and nosebleeds
• Delayed physical and intellectual development
• Swollen abdomen
• Facial deformities and bone deformities
• Behavioral problems, including hyperactivity and aggression
• Severe intellectual disabilities
• Muscle problems
• Neurological problems
• Cardiomegaly
• Hepatomegaly (enlarged liver) and splenomegaly (enlarged spleen)
• Hearing loss and vision loss

While these symptoms are most commonly related with lysosomal storage disorders, other health conditions can cause them as well. Individuals who have one or many of these symptoms should see their doctor for diagnosis and testing.

Causes

Genetic mutations are responsible for lysosomal storage disorders, and most of these diseases are inherited in an automatic recessive manner.

• Gaucher's disease is caused by a deficiency in the enzyme, glucocerebrosidase which breaks down glucocerebroside, a fat.
• Those with Hurler syndrome have a deficiency in the enzyme, lysosomal alpha-L-iduronidase which breaks down sugars called glycosaminoglycans.
• Tay-Sachs disease is caused by a mutation in the HEXA gene which makes beta-hexosaminidase A enzyme which helps break down fats, GM2 (ganglioside).
• Pompe disease is caused by mutations in the GAA gene which produces the alpha-glucosidase enzyme which breaks down glycogen.
• People with Morquio syndrome lack galactosamine-6-sulfatase or beta-galactosidase which process glycosaminoglycans.

Diagnosis & Tests

Doctors can diagnose diagnosis lysosomal storage disease during pregnancy (prenatal diagnosis), in newborns, and children. Medical professionals will assess patients for a variety of symptoms.

Echocardiograms may be conducted to assess heart abnormalities. Abdominal ultrasonography may be done to assess the presence of an enlarged spleen and/or liver. Neurological examinations may be done to detect intellectual disabilities/cognitive impairments and epilepsy. Eye examinations may be conducted to detect abnormalities of the eye (such as cherry-red spots characteristic of Tay-Sachs disease).

Blood tests and clinical urine tests can be done to detect abnormal levels of enzymes. Magnetic resonance imaging (MRI) scans of the brain can be used to detect brain abnormalities. Tissue biopsy is the removal of sample tissues from the body of the patient and the examination of the sample under a microscope.

Treatment & Therapy

Research is underway to find the cure for lysosomal storage disorders. However, there are therapies that significantly enhance the quality of life for those affected by this health problem. Bone marrow transplantation (BMT) can be effective in stimulating the body to create new cells that contain the deficient enzymes. Pyrimethamine is a medication that may be able to increase the amount of the missing enzyme associated with Tay-Sachs disease.

Substrate synthesis inhibition therapy can help remove substances from the body that accumulate due to the deficiency of the enzyme that metabolizes those substances. Examples include miglustat and Eliglustat which are used to treat Gaucher's disease. Enzyme replacement therapy (ERT) replaces the enzymes the body is deficient in. These are usually administered intravenously.

Physical therapy, occupational therapy, special education, and speech therapy may all be utilized to address various symptoms of these disorders. Dialysis and surgery may also be recommended depending on the manifestation of symptoms associated with these disorders.

Prevention & Prophylaxis