GAUCHERS DISEASE

GAUCHERS DISEASEBiochemistry LabBy Group 1What is Gauchers Disease?Gaucher disease is alipid storage diseasecharacterized by the deposition of glucocerebroside in cells of the macrophage-monocyte system. The disorder results from the deficiency of a specific lysosomal hydrolase, glucocerebrosidase (also termed acid beta-glucosidase, glucosylceramidase).Gaucher disease occurs in 1 in 50,000 to 100,000 people in the general population. Occurs more frequently in people of Ashkenazi Jewish decent.Gauchers disease has traditionally been divided into the following 3 clinical subtypes, delineated by the absence or presence of neurologic involvement and its progression:Type 1 Non-neuronophatic Type 2 Acute NeuronophaticType 3 Chronic Neuronophatic

However, some cases do not fit precisely into one of these categories. All forms of Gaucher disease are autosomal recessively inherited.

Types of Gauchers DiseaseType 1 Most common form of Gauchers DiseaseAlso called Non-neuronopathic Gauchers DiseaseThe signs and symptoms of this condition range from mild to severe and may appear anytime from childhood to adulthood.Type 2 (Acute Neuronophatic)usually causes life-threatening medical problems beginning in infancy.

Type 3 (Chronic Neuronophatic)tends to progress more slowly than type 2.

Signs and SysmtomsThe signs and symptoms of Gaucher disease are a result of the progressive accumulation of Gaucher cells in the body. Gaucher cells typically accumulate in the spleen, liver, and bone marrow. However, they may also collect in other tissues, including the lymphatic system, lungs, skin, eyes, kidney, heart, and in rare instances, the nervous system.Symptoms can appear at any age, but usually are first noticed in childhood or adolescence. They include:

easy bleeding and bruisingexcessive fatigueanemiaweak bones fracturing too easilybone and joint painenlargement of the belly through increase in the volume of spleen and liver.The type and severity of symptoms can vary widely among individuals. Some individuals do not experience any symptoms until they are elderly, while others may develop life-threatening conditions during childhood. Gaucher disease is progressive and, if left untreated, will usually become worse over time.Signs of Gaucher disease may include abnormal blood tests such as too few red blood cells and/or platelets, or abnormalities on X-ray pictures such as bone deformity.Pathophysiology

Ceramide- synthesized in the ER from the amino acid Ser

CausesAutosomal recessive pattern

Even when both parents are carriers, there's still only a 25 percent chance that their child will develop the diseaseCausesGlucocerebrosidase deficiency is due to mutations in GBA (Glucosidase Beta Acid Gene; the structural gene that encodes the enzyme). Widespread accumulation of glucosylceramide-laden macrophages results from the enzyme deficiency

Risk FactorsThe risk of having type 1 Gaucher's disease or being a carrier is higher if you're of Eastern or Central European Jewish (Ashkenazi) ancestry. Types 2 and 3 can occur in any ethnic group, except for a certain form of type 3 that's more common in people of Swedish descent.A family history of any type of Gaucher's disease increases the risk of being either a carrier of Gaucher's or of developing the disease.

ComplicationsAll types of Gaucher's disease tend to be progressive. Possible complications depend on the type of Gaucher's disease.

Complication for all types-Bone pain, which can become severe and may be associated with fractures.-A tendency to bleed, which may result in repeated hemorrhaging in the nostrils or nasal cavities, or bruising in the skin (ecchymosis).-An increased risk of certain cancers. Older people with Gaucher's disease may have an increased likelihood of developing certain types of cancer, particularly multiple myeloma uncontrolled multiplication of plasma cells.Complications for type 2Complications that are more likely to occur in people with type 2 Gaucher's disease often include serious neurological complications, such as:SeizuresDifficulty walkingSwallowing problemsAs these problems progress and become more severe, they can become debilitating and lead to death.Complications of type 3People with type 3 Gaucher's disease are more likely to develop calcification of heart valves, which damages the valves and makes it increasingly difficult for them to open fully and function properly.

DiagnosisThe average age at diagnosis is