Gaucher's disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes, which is often a target for intracellular parasites). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy.
The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females. About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is 1 in 450.[1]
Gaucher's disease is the most common of the lysosomal storage diseases.[2] It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids.[3]
The disease is named after the French physician Philippe Gaucher, who originally described it in 1882.[4]
Signs and symptoms
Painless hepatomegaly and splenomegaly: the size of the spleen can be 1500–3000 g, as opposed to the normal size of 50–200 g. Splenomegaly may decrease the affected individual's capacity for eating by exerting pressure on the stomach. While painless, enlargement of spleen increases the risk of splenic rupture.
Hypersplenism and pancytopenia, the rapid and premature destruction of blood cells, leads to anemia, neutropenia, leukopenia, and thrombocytopenia (with an increased risk of infection and bleeding).
Cirrhosis of the liver is rare.
Severe pain associated with joints and bones occurs, frequently presenting in hips and knees.
Neurological symptoms occur only in some types of Gaucher's (see below):
Type I: impaired olfaction and cognition
Type II: serious convulsions, hypertonia, intellectual disability, and apnea
Type III: muscle twitches known as myoclonus, convulsions, dementia, and ocular muscle apraxia
Parkinson's disease is recognized as being more common in Gaucher's disease patients and their heterozygous carrier relatives.[5]
Osteoporosis: 75% of p
2. Fatty change is characterized by the appearance of fat
which is demonstrable in the Cytoplasm of
parenchymal cells.
Fatty change is often seen in liver b/c it is the major
organ involved in the fat metabolism.
Definition of Fatty change
3. •1. Conditions with excess fat
•Obesity.
•Diabetes mellitus
•Congenital hyperlipidaemia
Etiology of Fatty change
4. •Alcohol liver disease
•Starvation
•Malnutrition
•. Chronic illness.
•Acute fatty liver in late pregnancy
•Hypoxia (anemia and cardiac failure)
•Hepatotoxins (carbon tetrachloride , chloroform , ether , aflatoxin
and other poisons.)
2.Liver cell damage
5. Gross – Fatty liver is enlarged.
• Tense , glistening capsule , rounded margin.
C/S – Bulge out , pale yellow , greasy on touch
Morphology
6.
7. Microscopic –
• Numerous lipid vacoule in cytoplasm of
hepatocyte.
• Vacoules around nucleus (microvesicular).
• Large vacoules to periphery (macrovesicular)
• Fatty cyst.
• Lipogranuloma.
• Fat deposited can be demonstrated by special
stains.
9. •It is done on fresh tissue or Frozen Section .
•Stains used in Frozen Sections are
(1) Sudan III – Black
(2) Scarlet Red - Red
(3) Oil Red - Red
•It is also seen under polarizing microscope
Special stains
