Gaucher's disease

Gaucher disease
Other names	Gaucher's disease
Acid beta-glucosidase
Specialty	Endocrinology, neurology
Symptoms	Hepatosplenomegaly, hypersplenism, pancytopenia, joint pain, neurological symptoms (usually mild), yellowish skin, and osteoporosis
Complications	Cirrhosis, splenic rupture, bleeding, and infections
Usual onset	Young adulthood (Type I), infancy (Type II)
Duration	Lifelong
Types	Type I, type II, type III
Causes	Glucocerebrosidase deficiency
Risk factors	Having parents with the disease or are carriers of the disease
Diagnostic method	Genetic testing
Differential diagnosis	SMPD1-associated Niemann–Pick disease, Fabry disease
Prevention	Gene editing
Treatment	Enzyme replacement therapy
Medication	Alglucerase, imiglucerase, velaglucerase, taliglucerase alfa, miglustat, and eliglustat
Prognosis	Slightly shortened life expectancy (type I), death in early childhood (type II)
Frequency	1 in 100 people are carriers

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]