About acid beta-glucosidase deficiency
What is acid beta-glucosidase deficiency?
Gaucher disease is a rare, inherited metabolic disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids), specifically the glycolipid glucocerebroside, throughout the body especially within the bone marrow, spleen and liver. The symptoms and physical findings associated with Gaucher disease vary greatly from case to case. Some individuals will develop few or no symptoms (asymptomatic); others may have serious complications. Common manifestations of Gaucher disease include an abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of circulating red blood cells (anemia), low levels of platelets(thrombocytopenia), and skeletal abnormalities. Platelets are blood cells that promote clotting and patients with thrombocytopenia may develop bleeding problems. Three separate forms of Gaucher disease have been identified and are distinguished by the absence of, or the presence and extent of, neurological complications. All three forms of Gaucher disease are inherited as autosomal recessive traits.
Gaucher disease is categorized as a lysosomal storage disorder. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or "digest" nutrients, including certain complex carbohydrates and fats. In Gaucher disease certain sugar (glucose) containing fat, known as glycolipids, abnormally accumulate in the body because of the lack of the enzyme, glucocerebrosidase. This accumulation or "storage" of lipids leads to the various symptoms or physical findings associated with a lysosomal storage disease. Gaucher disease is the most common type of lysosomal storage disorder.
What are the symptoms for acid beta-glucosidase deficiency?
There are different types of Gaucher disease, and signs and symptoms of disease vary widely, even within the same type. Type 1 is by far the most common.
Siblings, even identical twins, with the disease can have different levels of severity. Some people who have Gaucher disease have only mild or no symptoms.
Most people who have Gaucher disease have varying degrees of the following problems:
- Abdominal complaints. Because the liver and especially the spleen can enlarge dramatically, the abdomen can become painfully distended.
- Skeletal abnormalities. Gaucher disease can weaken bone, increasing the risk of painful fractures. It can also interfere with the blood supply to your bones, which can cause portions of the bone to die.
- Blood disorders. A decrease in healthy red blood cells (anemia) can result in severe fatigue. Gaucher disease also affects the cells responsible for clotting, which can cause easy Bruising and nosebleeds.
More rarely, Gaucher disease affects the brain, which can cause abnormal eye movements, muscle rigidity, swallowing difficulties and seizures. One rare subtype of Gaucher disease begins in infancy and typically results in death by 2 years of age.
What are the causes for acid beta-glucosidase deficiency?
Gaucher disease is passed along in an inheritance pattern called autosomal recessive. Both parents must be carriers of a Gaucher changed (mutated) gene for their child to inherit the condition
What are the treatments for acid beta-glucosidase deficiency?
While there's no cure for Gaucher disease, a variety of treatments can help control symptoms, prevent irreversible damage and improve quality of life. Some people have such mild symptoms that they don't need treatment.
Your doctor likely will recommend routine monitoring to watch for disease progression and complications. How often you'll need to be monitored will depend on your situation.
Many people who have Gaucher disease have seen improvements in their symptoms after beginning treatment with:
- Enzyme replacement therapy. This approach replaces the deficient enzyme with artificial ones. These replacement enzymes are given in an outpatient procedure through a vein (intravenously), typically in high doses at two-week intervals. Occasionally people have an allergic or hypersensitivity reaction to enzyme treatment.
- Miglustat (Zavesca). This oral medication appears to interfere with the production of fatty substances that build up in people with Gaucher disease. Diarrhea and weight loss are common side effects.
- Eliglustat (Cerdelga). This drug also seems to inhibit the production of fatty substances that build up in people with the most common form of Gaucher disease. Possible side effects include fatigue, headache, nausea and diarrhea.
- Osteoporosis drugs. These types of medication can help rebuild bone weakened by Gaucher disease.
Surgical and other procedures
If your symptoms are severe and you're not a candidate for less invasive treatments, your doctor might suggest:
- Bone marrow transplant. In this procedure, blood-forming cells that have been damaged by Gaucher disease are removed and replaced, which can reverse many of Gaucher signs and symptoms. Because this is a high-risk approach, it's performed less often than is enzyme replacement therapy.
- Spleen removal. Before enzyme replacement therapy became available, removing the spleen was a common treatment for Gaucher disease. Now this procedure typically is used as a last resort.
What are the risk factors for acid beta-glucosidase deficiency?
People of Eastern and Central European Jewish (Ashkenazi) ancestry are at higher risk of developing the most common variety of Gaucher disease.
Is there a cure/medications for acid beta-glucosidase deficiency?
There is no cure for this condition; however certain treatments can aid in managing the symptoms and preventing irreversible damage.
- Enzyme Replacement/Enhancement Therapy is provided intravenously to reduce the liver and spleen size, and skeletal abnormalities and reverse other symptoms.
- Substrate Reduction Therapy to treat Type 2 Gauchers’ disease.
- Hematopoeitic stem cell transplantation to revive the blood cell production
- Blood Transfusion may be followed for patients with severe anemic symptoms.
- Joint replacement therapy to enhance the mobility of the joints.
- Medications including antibiotics and antiepileptics may be used to treat infections and seizures, respectively.
- Gene Therapy’s efficiency in treating Acid Beta-Glucosidase deficiency may be a future step.
The primary objective of this treatment is to eliminate or improve the symptoms, prevent irreversible complications and enhance the overall health and quality of life. Regular monitoring will be performed to assess the efficiency of the therapy on an individual basis.