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At a glance

Most common inherited lipid storage disease. It is particularly common in Ashkenazi Jewish people. Characterized by accumulation of glucocerebrosides (derived from red blood cells) in many tissues, especially the macrophages in the bone marrow. Attention should be given to hematological parameters in particular with children with mild, nonneuronopathic Type I and severe neuronopathic Type III Gaucher disease in an attempt to minimize postoperative bleeding, the most serious complication.

Synonym

Sphingolipidosis I.

Classification

There are four types of Gaucher Disease:

  • Gaucher Disease Type I (Noncerebral Juvenile Gaucher Disease; Glucocerebrosidase Deficiency; Acid Beta Glucosidase Deficiency; GBA Deficiency): 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): 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 of life.

  • Gaucher Disease Type III (Juvenile and Adult Cerebral Gaucher Disease; Chronic Neuronopathic Gaucher Disease; Subacute Neuronopathic Gaucher Disease; Norrbottnian Type Gaucher Disease): 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 variable.

  • Perinatal Lethal Gaucher Disease: 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 cases.

History

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.

Incidence

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.

Genetic inheritance

Autosomal recessive; locus is the long arm of chromosome ...

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