Gaucher Disease

  • Medical Author:
    Melissa Conrad Stöppler, MD

    Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

  • Medical Editor: William C. Shiel Jr., MD, FACP, FACR
    William C. Shiel Jr., MD, FACP, FACR

    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

Gaucher disease facts

  • Gaucher disease is an inherited (genetic) condition that is due to a deficiency in the enzyme glucocerebrosidase.
  • Gaucher disease leads to the accumulation of fatty substances in certain organs.
  • Signs and symptoms of Gaucher disease include
  • Signs and symptoms vary among people with Gaucher disease.
  • There are several types of Gaucher disease including type 1, 2, 3 Gaucher disease; perinatal lethal Gaucher disease, and cardiovascular Gaucher disease.
  • The most common type of Gaucher disease is type 1, and this type typically does not affect the nervous system.
  • Type 2 Gaucher disease and perinatal lethal Gaucher disease are rare and severe forms of the disease.
  • Gaucher disease is inherited in an autosomal recessive manner.
  • Gaucher disease is most common in people of Ashkenazi Jewish descent, affecting about 1 out of every 855 people. In the non-Jewish population, Gaucher disease affects 1 out of every 40,000 people.
  • Enzyme replacement therapy (ERT) is the main treatment for Gaucher disease.
  • Those with family members affected with Gaucher disease may want to consider genetic counseling and screening for the genetic mutation.

Types of Genetic Disorders

There are a number of types of genetic inheritance and associated disorders. For example, single gene or monogenetic inheritance disorders include:

  • Iron overload (hemochromatosis)
  • Sickle cell anemia
  • Marfan syndrome
  • Huntington's disease
  • Cystic fibrosis

Another type of genetic inheritance is multifactorial inheritance disorders, for example:

  • Diabetes
  • Cancer
  • Alzheimer's disease
  • Cancer

What is Gaucher disease?

Gaucher disease (sometimes called Gaucher's disease) is an inherited condition that results in the abnormal accumulation of fatty substances known as glycolipids in different body tissues due to a deficiency of an enzyme known as glucocerebrosidase. There are several different types of the condition, and the signs and symptoms that arise due to the sphingolipid accumulation vary widely. Gaucher disease is due to a genetic defect in a gene known as GBA1. Gaucher disease belongs to a class of diseases called lysosomal storage diseases, named after a type of cell that is affected by the buildup of glycolipids.

What are the symptoms of Gaucher disease?

The main signs and symptoms of Gaucher disease are:

People with type 1 Gaucher disease usually first notice painless enlargement of the spleen, anemia, or bleeding and bruising due to low platelet count. The enlargement of the spleen may become severe and may limit a child's growth due to the energy required to sustain the enlarging spleen. An enlarged liver and abnormal liver function tests are also characteristic signs. Skeletal involvement by Gaucher disease is common and can take the form of bone pain, fractures of bone, and a defect of the thigh bone (femur).

How is Gaucher disease inherited?

Gaucher disease in inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the defective gene in order for a child to be affected.

How common is Gaucher disease?

In people of Ashkenazi Jewish descent Type 1 Gaucher disease (see below) is more common, and affects 1 out of every 855 people. About 1 out of every 15 people of Ashkenazi Jewish descent are thought to be carriers of the genetic mutation responsible for Gaucher disease. The other types of Gaucher disease do not occur more frequently in people of Ashkenazi Jewish heritage. In the non-Jewish population, Gaucher disease affects 1 out of every 40,000 people.

What are the types of Gaucher disease?

Type 1 Gaucher disease

The most common form of the condition is type 1 Gaucher disease. About 90% of people with the condition have this type. The signs and symptoms of this type can vary in their extent of severity. The symptoms can appear in childhood or may be delayed until adulthood. The brain and spinal cord, or central nervous system (CNS), are typically not affected by the disease, so this type is sometimes referred to as non-neuronopathic, meaning that the condition does not affect nerve cells.

Type 2 Gaucher disease (acute neuronopathic form)

This rare type of Gaucher disease affects the nervous system and is termed neuronopathic Gaucher disease. Signs and symptoms include seizures, eye movement problems, and brain damage. Type 2 Gaucher disease is very severe and typically leads to life-threatening medical problems that begin in infancy.

Type 3 Gaucher disease (chronic neoronopathic form)

Like Type 2 Gaucher disease, type 3 Gaucher is a neuronopathic for of Gaucher disease that affects the nervous system, but symptoms do not progress as rapidly as in Type 2. The signs and symptoms may appear in infancy or later in childhood.

Perinatal lethal Gaucher disease

Perinatal lethal Gaucher disease is the most severe form of the condition. With this type, the life-threatening conditions can appear before birth. There may be excessive swelling and fluid accumulation in the fetus (hydrops fetalis) prior to birth. Other features can include severe neurological disturbances, abnormal facial features, hepatosplenomegaly, and dry or scaly skin. Most infants with this form of the condition survive only a few days after birth.

Cardiovascular Gaucher disease

This type of Gaucher disease, considered a rare subgroup of type 3 disease, primarily affects the heart, leading to calcification or hardening of the heart valves. Sometimes, symptoms and signs of other types of Gaucher disease may also be present.

What causes Gaucher disease?

All of the types of Gaucher disease are caused by a deficiency of the enzyme glucocerebrosidase, leading to an abnormal buildup of fatty substances, glycolipids, in the body cells. Mutations in the gene known as GBA1 are the cause of the deficient enzyme, and over 300 different GBA1 mutations have been identified in people with Gaucher disease. The mutations are inherited (passed from parent to offspring) in an autosomal recessive manner (see above). The four most common mutations of GBA1 gene are N370S, L444P, 84gg and IVS2[+1]. DNA analysis for these 4 mutations can detect 90%-95% of the mutations associated with Gaucher Disease in the Ashkenazi Jewish population, and 50%-75% of the associated mutations in the general population.

Which specialties of doctors treat Gaucher disease?

Patients with Gaucher disease may be treated by a number of different medical specialists, depending on the type of the disease and the specific symptoms and signs of the condition they experience. These may include pediatricians, neonatologists, internists, geneticists, neurologists, orthopedists, critical care specialists, cardiologists, and hematologists. Most patients who are treated with enzyme replacement therapy will have their treatment plan managed by a geneticist and/or hematologist.

Is there a test to diagnose Gaucher disease?

A blood test is used to make the diagnosis of Gaucher disease. The enzyme assay test measures activity of the glucocerebrosidase enzyme in certain white blood cells. Having less than 15% of normal enzyme activity is diagnostic for Gaucher disease. Genetic analysis is also done to establish the specific type of mutations in the GBA1 gene.

What is the treatment for Gaucher disease?

There is no cure for Gaucher disease, but medical treatments are available. Enzyme replacement therapy (ERT) is the primary form of treatment for people with type 1 and Gaucher disease and for the non-neurologic symptoms of type 3 Gaucher disease. The drug is given intravenously, generally at 2-week intervals. There are three ERT drugs available, imiglucerase (Cerezyme), velaglucerase alfa (VPRIV), and taliglucerase alfa (Elelyso).

Other medications available to treat Gaucher disease include drugs that block the production of the sphingolipids that accumulate in cells and cause symptoms. These drugs are known as glucosylceramide synthase inhibitors and are taken by mouth. Two drugs in this class are miglustat (Zavesca) and eliglustat (Cerdelga).

Formerly, the condition was often treated by surgical removal of the spleen (splenectomy). However, this is typically not necessary given the availability of ERT.

What is the prognosis, or life-expectancy, for someone with Gaucher disease?

The prognosis for people with type 1 or type 3 Gaucher disease who receive treatment is very good. Many people with Gaucher disease have few symptoms and can expect a normal life span even without treatment. One study estimated life expectancy at birth for people with type 1 Gaucher disease to be 68 years, compared with 77 years in the general population. Type 2 Gaucher disease usually results in death within the first few years of life.

Should I talk to my family about Gaucher disease?

As with any inherited disease, sharing information with family members is important. If Gaucher disease is identified within a family, other family members may wish to be tested to find out if they are carriers for the gene mutation. Carrier testing is simple and can be performed on a sample of blood or saliva. Your health-care professional can help you decide if carrier testing is appropriate and may refer you to a genetic counselor for more information.

What help is available for patients and their families living with Gaucher disease?

Living with Gaucher disease or any chronic illness is stressful for both patient and family. Getting help and support are important for achieving the best quality of life possible while facing the challenges and that the illness brings. The National Gaucher Foundation (800-504-3189) offers educational and support services for affected families, including a mentor program, an electronic pen pal program for young adults, real-life patient stories, and numerous educational programs.

What other names are used to refer to Gaucher disease?

Gaucher disease has been referred to in the medical literature by a number of different names. These include:

  • cerebroside lipidosis syndrome
  • Gaucher splenomegaly
  • Gaucher syndrome
  • Gaucher's disease
  • Gauchers disease
  • GD
  • glucocerebrosidase deficiency
  • glucocerebrosidosis
  • glucosyl cerebroside lipidosis
  • glucosylceramidase deficiency
  • glucosylceramide beta-glucosidase deficiency
  • glucosylceramide lipidosis
  • kerasin histiocytosis
  • kerasin lipoidosis
  • kerasin thesaurismosis
  • lipoid histiocytosis (kerasin type)

REFERENCES:

National Gaucher Foundation. "Testing for Gaucher disease."
<http://www.gaucherdisease.org/gaucher-disease-testing.php>

Sidransky, E., MD., et al. "Gaucher disease. Medscape. Updated Nov 24, 2014.
<http://emedicine.medscape.com/article/944157-overview>

US National Library of Medicine; Genetics Home Reference. "Gaucher disease." Updated July 5, 2016.
<https://ghr.nlm.nih.gov/condition/gaucher-disease#>

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Reviewed on 7/5/2016
References
REFERENCES:

National Gaucher Foundation. "Testing for Gaucher disease."
<http://www.gaucherdisease.org/gaucher-disease-testing.php>

Sidransky, E., MD., et al. "Gaucher disease. Medscape. Updated Nov 24, 2014.
<http://emedicine.medscape.com/article/944157-overview>

US National Library of Medicine; Genetics Home Reference. "Gaucher disease." Updated July 5, 2016.
<https://ghr.nlm.nih.gov/condition/gaucher-disease#>

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