Gaucher Disease

Gaucher Disease - a genetic disease in which fatty substances (lipids) accumulate in cells and in some organs. Disease  Gaucher disease is caused by a recessive mutation in the gene
 Gaucher is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (subgroup of lysosomal storage diseases), as manifested in dysfunctional metabolism of sphingolipids.

The disorder is characterized by fatigue, anemia, low blood platelets, enlargement of the liver and spleen. This is due to an inherited deficiency of the enzyme glucocerebrosidase, which acts on glucosylceramide fatty acids. When the enzyme is defective, glucosylceramide accumulates particularly in leukocytes, usually macrophages (mononuclear leukocytes). Glucosylceramide may accumulate in the spleen, liver, kidney, lung, brain and bone marrow.

Manifestations of Gaucher disease may be enlargement of the spleen and liver, severe neurologic complications, swelling of lymph nodes and adjacent joints, bloating, brownish color of the skin, anemia, low platelet count in the blood and the sclera.

The disease is caused by a recessive mutation in a gene located on chromosome 1, and affects both men and women. About 1 in 100 people in the world is a carrier of Gaucher disease. The disease is named after the French doctor Philippe Gaucher, originally described it in 1882.

Types of Gaucher Disease

Gaucher disease has three common clinical subtypes: type I, type II and type III.

Type I is the most common form of the disease, occurring with a frequency of 1 in 50,000 births. Symptoms of Gaucher disease type that may occur at an early age, or in adulthood and include:

  • Increased hepatic and greatly enlarged spleen;
  • The weakness of the skeletal bones;
  • Anemia, thrombocytopenia and leukopenia;
  • Renal disease;
  • Fatigue.

Type II usually begins to occur in the first six months of the date of birth and occurs at a frequency of approximately 1 in 100,000 births. Symptoms of this type of Gaucher disease include:

  • Enlarged liver and spleen;
  • The extensive and progressive brain damage;
  • Violations of eye movement, spasticity, cramps and stiffness of limbs;
  • Weak ability to suck and swallow.

Affected children usually die before the age of 2 years.

Type III (the chronic neuropathic form) can begin at any time in childhood or even in adulthood, and occurs with a frequency of 1 in 100,000 births. Major symptoms include an enlarged spleen or liver disease, seizures, loss of coordination, trouble breathing, skeletal disorders, eye movements, blood diseases, including anemia.

The symptoms of Gaucher disease

Common symptoms of Gaucher disease include:

  • Painless hepatomegaly and splenomegaly - spleen size may be from 1500 to 3000 ml, in contrast to a standard size of 50-200 ml. Splenomegaly can reduce appetite by putting pressure on the stomach and spleen expansion increases the risk of rupture of the spleen;
  • Hypersplenism pancytopenia and - a rapid and premature destruction of blood cells, leading to anemia, neutropenia, leukopenia, and thrombocytopenia (with an increased risk of infection and bleeding);
  • Cirrhosis of the liver;
  • Severe pain in the joints and bones, often in the hip and knee joints;
  • Neurological symptoms;
  • Type II: severe cramps, hypertension, mental retardation, sleep apnea;
  • Type III: muscle twitching, seizures, dementia, apraxia of eye muscles;
  • Osteoporosis;
  • The yellowish-brown pigmentation of the skin.

Treatment of Gaucher Disease

Treatment of Gaucher disease subtype 1 and 3 may start with intravenous recombinant glucocerebrosidase enzyme replacement, which can significantly reduce the size of the liver and spleen, skeletal abnormalities and draw  Gaucher disease - a genetic disorder
   reverse other manifestations. The procedure costs about $ 200,000 for a single patient and should be repeated annually throughout the life of the patient. Also, treatment of Gaucher disease is carried out using the drug Velaglucerase Alfa, which has been approved as an alternative treatment since February 2010.

Also, the treatment of Gaucher disease can be a successful bone marrow transplant, which treats not the neurological manifestations of the disease, as in the procedure introduced monocytes with an active beta-glucosidase. However, this procedure carries significant risks and is rarely recommended for Gaucher disease.

Surgery to remove the spleen (splenectomy) is required in rare cases, if the patient has anemia or when enlarged organ affects the health of the patient. Blood transfusions may be the case for patients with symptoms of anemia. Also, in some cases, joint replacement surgery to improve mobility and quality of life.

Other treatments for Gaucher disease include antibiotics against infections protivoepileptikov, bisphosphonates for bone lesions, and liver transplantation.

Gaucher disease also is treated with oral administration of drugs that act at the molecular level. Miglustat is one of these drugs and has been approved for the treatment of Gaucher disease in 2003.