Rare Disease Report


Rare Diseases of Lysosomal Storage

Lysosomal diseases, or lysosomal storage disorders, are a group of more than 50 known rare genetic medical conditions, each of which has slightly different symptoms, treatment, and prognosis. All involve problems with lysosomes, structures inside cells that break down substances that need to be removed.

Although all lysosomal storage disorders are rare conditions, they are more common in certain ethnic groups and regions of the world. For example, Tay-Sachs disease is about 100 times more common in people of Ashkenazi Jewish descent than it is in the general population. As a group, lysosomal diseases occur in about 1 in 8000 live births.

The symptoms of lysosomal diseases result from the buildup of substances within cells that the lysosomes are unable to remove. This can happen because a specific enzyme to break down certain substances does not work or there is a problem moving the contents of lysosomes correctly. Lysosomal disorders can cause seizures, mental retardation, skeletal deformations, blood cell abnormalities, kidney problems, macular degeneration, and enlargement of the liver and spleen, among others.

Because of the wide variety of systems involved, the treatment of a lysosomal disease requires a team-based approach, with a patient’s care coordinated by several specialists with expertise in these conditions. For example, a patient might need to see a neurologist for optimal seizure control and a cardiologist for treatment of cardiac symptoms.

Diagnosis Challenges

Although the diagnosis of a lysosomal disease can take days or weeks, usually it takes much longer. In a young patient with serious symptoms, the urgent diagnostic hunt begins almost immediately.

Other people with more mild disease might not notice any symptoms until later childhood or adulthood, so their search for a diagnosis is delayed. Even if symptoms are obvious, patients sometimes undergo a wide array of tests before a correct diagnosis emerges. An atypical case of a particular lysosomal storage disorder may take an exceptionally long time to be diagnosed.

Physicians should consider the possibility of a lysosomal disease in patients with neurological problems, kidney problems, or muscle degeneration, especially if unexplained cardiomyopathy, an enlarged liver or spleen, or skeletal deformations are also present. Diagnosis can be challenging because symptoms of lysosomal diseases vary significantly even in patients with the same condition and these symptoms may resemble those of more common diseases. Also, lysosomal diseases usually cannot be diagnosed based on physical exam and basic blood tests alone. Often, no known medical history of lysosomal disease exists in a patient’s family, and the clinician must first consider the possibility of a specific lysosomal disease before the appropriate diagnostic test can be given. Usually, this is a specific blood test, which can detect a low level of the affected enzyme or a specific genetic abnormality.

The diagnostic process often begins with medical imaging or other tests, so that the clinician can gather information about the various organ systems affected. A general physician might initially refer the patient to one or more specialists—such as a neurologist or nephrologist—for assistance with initial care and diagnosis.

After diagnosis, other family members may require testing, as well; many lysosomal diseases are autosomal recessive conditions. Genetic testing can help individuals make family planning decisions. Prenatal testing is a new possibility for fetuses known to be at risk for certain lysosomal storage diseases. In some cases, genetic testing may even identify family members who have a mild and undiagnosed case of the disorder.

Online Resources

List of rare conditions:

List of FDA-approved orphan drugs:

National Organization for Rare Disorders:


Each lysosomal storage disease requires its own specific treatment strategy, which may include multiple components. Treatments for lysosomal diseases fall into 2 main categories: supportive treatments of disease symptoms and specific treatments of the underlying disorder. For many lysosomal storage diseases, supportive treatment is the only type currently available.

Supportive treatments may involve a variety of different subspecialties. For example, a patient with Tay-Sachs might need a seizure-preventing medication, another patient with mucopolysaccharidosis (MPS) might need physical therapy, and a patient with Gaucher disease might need surgery to remove an enlarged spleen.

Some other disease-specific treatments include:

  • Bone marrow transplantation to increase the functional enzyme in Hurler syndrome
  • Enzyme replacement in Fabry disease (agalsidase beta/ Fabrazyme)
  • Enzyme replacement in Pompe disease (alglucosidase alfa/ Myozyme)
  • Drug therapy to reduce the accumulated substance in Gaucher disease (miglustat/Zavesca)
  • Drug therapy to reduce the accumulated substance in cystinosis (cysteamine bitartrate/ Procysbi)

Clinical Trials

  • Research on lysosomal storage diseases is ongoing. Some current clinical trials studying potential new treatments for these conditions include:
  • Migalastat: Fabry disease
  • Sebelipase alfa: lysosomal acid lipase deficiency
  • Albuterol: Pompe disease
  • SBC-103: Sanfilippo B syndrome

Advocacy Support and Information

Advocacy groups provide an important resource for patients, caregivers, and clinicians by supplying introductory educational materials and practical advice for dealing with these conditions, as well as more detailed information about recent research papers, current clinical trials, etc. They also offer social support and the opportunity to learn from other families who have experience dealing with these diseases.

Below are some advocacy groups for those with lysosomal storage diseases:

Cystinosis Foundation:

LAL SOLACE (support organization for lysosomal acid lipase deficiency):

National MPS Society (for mucopolysaccharidosis):

National Niemann-Pick Disease Foundation:

Jonah’s Just Begun (for Sanfilippo syndrome):

For a more complete list, see Appendix B of this resource guide.
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