2. Definition
Gaucher (go-SHAY) disease is the result of a buildup of certain fatty
substances in certain organs, particularly your spleen and liver. This
causes these organs to enlarge and can affect their function.The fatty
substances also can build up in bone tissue, weakening the bone and
increasing the risk of fractures.
3. History
• The disease was first recognized by the French doctor Philippe Gaucher, who
originally described it in 1882 and lent his name to the condition.
• In 1902, its mode of inheritance was discovered by Nathan Brill.
• The neuronal damage associated with the disease was discovered in the
1920s, and the biochemical basis for the disease was elucidated in the 1960s
by Roscoe Brady.
• The first effective treatment for the disease, the drug alglucerase (Ceredase),
was approved by the FDA in April 1991.
• An improved drug, imiglucerase (Cerezyme), was approved by the FDA in
May 1994 and has replaced the use of Ceredase.
4. Epidemiology
• The prevalence is approximately 1/100,000.
• The annual incidence of GD in the general population is about 1/60,000,
but it can reach up to 1/1,000 in Ashkenazi Jewish populations.
5. Etiology
• GD is due to mutations in the GBA gene (1q21) that codes for a lysosomal
enzyme, glucocerebrosidase, or in very rare cases the PSAP gene that codes
for its activator protein (saposin C).
• The deficiency in glucocerebrosidase leads to the accumulation of
glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the
reticuloendothelial system of the liver, the spleen and the bone marrow
(Gaucher cells)
6. Symptoms
Major signs and symptoms include
• enlargement of the liver and spleen (hepatosplenomegaly),
• a low number of red blood cells (anemia),
• easy bruising caused by a decrease in blood platelets (thrombocytopenia),
lung disease, and
• bone abnormalities such as bone pain, fractures, and arthritis.
7. Risk factors
• People of Eastern and Central European Jewish (Ashkenazi) ancestry are at
higher risk of developing the most common variety of Gaucher disease.
8. Complications
Gaucher disease can result in:
• Delays in growth and puberty in children
• Gynecological and obstetric problems
• Parkinson's disease
• Cancers such as myeloma, leukemia and lymphoma
9. Types of Gaucher Disease
classify the disease according to one of three types:
• Type 1: Gaucher disease type 1 makes up the majority of cases in western
countries. Symptoms and signs can include bone and organ problems, but
brain development is normal. This form of the disease is treatable.
• Type 2: Also called acute infantile neuronopathic Gaucher disease, Gaucher
disease type 2 has an onset of central nervous system problems that are
typically fatal within 2 years. The central nervous system problems of type 2
are not treatable.
• Gaucher disease type 2 signs and symptoms include early onset brain damage
that is severe and rapidly worsening. Other signs include:
• Poor development,Seizures,Spasticity (jerking movements),Poor ability to
suck and swallow,Enlarged liver and spleen.
10. • Type 3: Gaucher disease type 3 is the most common variant of the disease worldwide.
Symptoms and signs can include bone and organ problems, as well as neurological
effects such as seizures. It typically has a later onset compared with type 2, and patients
may survive into adulthood.
• Gaucher disease type 3 has a later and more gradual onset compared with type 2. People
with Gaucher type 3 disease may survive into adulthood with a wide variety of signs and
symptoms.
• Major signs include:
• Seizures
• Skeletal irregularities
• Eye movement disorders
• Cognitive problems
• Poor coordination
• Enlarged liver and spleen
• Respiratory problems
11. Pathology
• Gaucher disease (GD) is a lysosomal storage disease. It corresponds to a
congenital deficit in β-glucocerebrosidase.
• This pathology should be considered in the presence of unexplained
splenomegaly, with or without signs of haemorrhage, skeletal manifestations
or hepatomegaly.
13. Diagnosis
Lab tests
• Blood samples can be checked for levels of the enzyme associated with
Gaucher disease. Genetic analysis can reveal whether you have the disease.
• Imaging Tests
• People diagnosed with Gaucher disease typically require periodic tests to track
its progression, including:
• Dual energy X-ray absorptiometry (DXA).
• This test uses low-level X-rays to measure bone density.
• MRI.
• Using radio waves and a strong magnetic field, an MRI can show whether the
spleen or liver is enlarged and if bone marrow has been affected.
14. • Preconception screening and prenatal testing
Treatment
• 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.
• will recommend routine monitoring to watch for disease progression and
complications. How often you'll need to be monitored will depend on situation.
• Medications
• Many people who have Gaucher disease have seen improvements in their
symptoms after beginning treatment with:
15. • 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.
16. Surgical and other procedures
• 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.
