Most common inherited lipid storage disease. It is
particularly common in Ashkenazi Jewish people. Accumulation of
glucocerebrosides (derived from red blood cells) in many tissues, especially
the macrophages in the bone marrow.
- Gaucher Disease Type I (Noncerebral Juvenile Gaucher Disease; Glucocerebrosidase Deficiency;
Acid Beta Glucosidase Deficiency; GBA Deficiency) is characterized by
hematologic abnormalities with hypersplenism, bone lesions, skin
pigmentation, and pingueculae (brown spots of Gaucher cells at corneoscleral
limbus). The disorder is particularly frequent in Ashkenazi Jews. The
disease has been diagnosed as early as in the first week of life and as late as
86 years of age.
- Gaucher Disease Type II (Infantile Cerebral Gaucher Disease; Acute Neuropathic Gaucher Disease) is
characterized by enlargement of the abdomen from hepatosplenomegaly and
neurologic signs such as retroflexion of the head, strabismus, dysphagia,
choking spells, and hypertonicity. Death usually occurs before the end of the second year
- Gaucher Disease Type III (Juvenile and Adult Cerebral Gaucher Disease; Chronic Neuronopathic Gaucher
Disease; Subacute Neuronopathic Gaucher Disease; Norrbottnian Type Gaucher
Disease) is characterized by hepatosplenomegaly that usually precedes
neurologic abnormalities, which include ataxia, spastic
paraplegia, grand mal and/or psychomotor seizures, supranuclear
ophthalmoplegia, and dementia. Supranuclear gaze palsies (ocular motor
apraxia) are characteristic of type III Gaucher disease. Age of onset is
- Perinatal Lethal Gaucher Disease is characterized by nonimmune hydrops fetalis. When
hydrops is absent, neurologic involvement begins in the first week of life and leads to
death within 3 months. Hepatosplenomegaly is a major sign and is associated with
ichthyosis, arthrogryposis, and facial dysmorphism in 35 to 43% of
Genetic disorder first described in 1882 by the French
physician Philippe Charles Ernest Gaucher. At least 34 mutations are known
to cause Gaucher disease, but only four (N370S, L444P, 84gg, IVS2[+1])
account for 95% of cases in the Ashkenazi Jewish population, and 50%
of cases in the general population. Enzyme
replacement therapy is available (mainly for type I). A clinical trial of
gene therapy is under progress.
Estimated at 1:60,000 live births (all
forms considered). The carrier rate for the mutations may be as high as 1 in
14 Ashkenazi Jews and 1 in 100 of the general population. Males and females
are equally affected. Incidence approximates up to 1:250 live births for type
I (in Ashkenazi Jews), 1:100,000 live births for type II and 1:50,000 for type III.
Autosomal recessive; locus is the long arm of
chromosome 1 at position 21 (1q21). Gene is 7 kb in length with 11 exons.
Missense mutation is the most common form.
In lysosomes, glucosylceramide is broken down by
acid beta-glucosidase (glucocerebrosidase) into ceramide and glucose. A
reduction in the catalytic function of acid beta-glucosidase leads to
glucosylceramide accumulation in monocytes and macrophages, which become
Gaucher cells. These engorged cells can be found in varying degrees
throughout the body and cause cell necrosis, mainly ...