GBA deficiency

Gaucher Disease

Clinical Characteristics
Ocular Features: 

Gaucher disease is often divided into three clinical types, I, II, and III although all are caused by mutations in the same gene.  Type I, sometimes called nonneuronopathic type I, has ocular features including white deposits in anterior chamber structures such as the corneal endothelium, pupillary margin, and the angle, as well as in the ciliary body.  Pingueculae can be prominent.  The perimacular retina often appears grayish and also can show some white spots.  These may also be seen in the posterior vitreous in at least some patients with type III  There may be pigmentary changes in the macula and uveitis occurs rarely.  Macular atrophy has been reported and the retinal vasculature may be abnormally permeable. Corneal opacities have been seen in some patients.  Oculomotor apraxia and abnormal opticokinetic responses are common in types II and III.  Visual acuity may be in the range of 20/200.

Other conditions with ataxia and oculomotor apraxia are: ataxia with oculomotor apraxia 1 (208920), ataxia with oculomotor apraxia 2 (602600), ataxia-telangiectasia (208900) and Cogan-type oculomotor apraxia (257550) which lacks other neurologic signs.

Systemic Features: 

This is a severe systemic disease with perinatal lethality in some patients.  The range of clinical heterogeneity is wide, however, and minimally affected adult patients have also been described.  Individuals with nonneuropathic type I lack central nervous system involvement.  They often do have hepatosplenomegaly and pancytopenia with bone marrow involvement which are common to all types.  The latter may be responsible for frequent bone fractures and other orthopedic complications such as vertebral compression.  Thrombocytopenia with bleeding complications contributes to the primary anemia which is also present.  Interstitial lung disease can be seen in type I disease but occurs in less than 5% of patients. This is the most common of the three types. 

Patients with type I Gaucher disease have an increased risk of cancer, especially those of the hematological system.  For example, the risk for multiple myeloma has been estimated to be 37 times higher than in the general population.  There is also evidence of an increased incidence of multiple consecutive cancers in this condition.  Enzyme replacement therapy may reduce the risk of malignancies.

Patient with types II (acute neuronopathic [230900]) and III (subacute neuronopathic [231000]) are more likely to have neurologic disease with bulbar and pyramidal signs and sometimes seizures.  In type II, onset is in infancy and lifespan is about 2 years.   They have hepatosplenomegaly with growth arrest and developmental delays after a few months.  The clinical signs in type III or subacute neuronopathic type the onset is later (2.5 years to adulthood) than in type II and progression of neurologic disease is slower.  Early childhood development may appear normal for several years until abnormal extraocular movements or seizures are observed.  Type III is sometimes called Norrbottnian type.


All three types of Gaucher disease are caused by mutations in the GBA (glucocerebrosidase) gene (1q21) and are inherited in an autosomal recessive pattern.

Evidence indicates that SCARB2, which codes for lysosomal integral membrane protein type 2 (LIMP-2), is a modifier of the phenotype in Gaucher disease.

Autosomal recessive
Treatment Options: 

Supportive care is required for all patients.  Splenectomy may be required for thrombocytopenia and blood transfusion can be helpful in severe anemia and excessive bleeding.  The course of disease is highly variable in all types, ranging from neonatal mortality to mild disease into adulthood, especially for individuals with type III.  Testing for deficiency in glucosylceramidase enzyme activity in leukocytes can be diagnostic.   Enzyme replacement or substrate reduction therapies can reduce the severity of clinical disease especially in type I disease but less so in types II and III.

Article Title: 

The clinical management of type 2 Gaucher disease

Weiss K, Gonzalez AN, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of type 2 Gaucher disease. Mol Genet Metab. 2014 Nov 14.  [Epub ahead of print] Review.

PubMed ID: 

A Mutation in SCARB2 is a Modifier in Gaucher Disease

Velayati A, Depaolo J, Gupta N, Choi JH, Moaven N, Westbroek W, Goker-Alpan O, Goldin E, Stubblefield BK, Kolodny E, Tayebi N, Sidransky E. A Mutation in SCARB2 is a Modifier in Gaucher Disease. Hum Mutat. 2011 Jul 27. doi: 10.1002/humu.21566. [Epub ahead of print]

PubMed ID: 
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