Gaucher disease type 3

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Gaucher disease type 3 is the subacute neurological form of Gaucher disease (GD; see this term) characterized by progressive encephalopathy and associated with the systemic manifestations (organomegaly, bone involvement, cytopenia) of GD type 1 (see this term).

The annual incidence of GD is about 1/60,000 and the prevalence is approximately 1/100,000. GD type 3 accounts for 5% of all patients with GD.

The clinical presentation is very heterogeneous. Neurological disease appears in childhood or adolescence, a much later onset than in GD type 2 (see this term). Encephalopathy can be the presenting sign of the disease or may occur later in the disease course. Some patients have moderate systemic involvement associated with ophthalmoplegia as the only neurological symptom. For the more severe forms, the neurological signs encountered are variable: supranuclear horizontal ophthalmoplegia, progressive myoclonic epilepsy, cerebellar ataxia, spasticity and dementia. GD type 3 is also associated with the clinical and biological signs of ''systemic'' disease, such as frequent asthenia, growth retardation or delayed puberty, splenomegaly and hepatomegaly. Bone anomalies may also be present and manifest as deformations, osteopenia, which sometimes leads to pathological fractures or vertebral compression, bone infarctions or even aseptic osteonecrosis. Involvement of other organs (rarely symptomatic pulmonary, renal and cardiac) is less common. Pancytopenia is frequent and involves varying degrees of thrombocytopenia (sometimes severe), anemia and, less frequently, leukoneutropenia. Polyclonal hypergammaglobulinemia is often present and is sometimes complicated by monoclonal gammapathy.

GD type 3 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that codes for the lysosomal enzyme, glucocerebrosidase. The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, spleen and the bone marrow (Gaucher cells).

Diagnostic methods involve ultrasound and magnetic resonance imaging (MRI) for initial evaluation and subsequent monitoring of hepatosplenomegaly, radiography and bone scintigraphy to detect bone lesions and complications, osteodensitometry for the evaluation of osteopenia of the lumbar spine and femoral neck, and cardiac ultrasound for the detection of pulmonary arterial hypertension. An increase in certain biological markers that are important both for the initial diagnosis and monitoring with or without treatment, is also observed: chitotriosidase, an angiotensin converting enzyme, ferritin and tartrate-resistant acid phosphatases. Diagnosis can be confirmed by demonstrating a deficit in the enzymatic activity of glucocerebrosidase in circulating leukocytes. In rare cases, genotyping may be of prognostic value: a patient with a homozygous L444P mutation in the GBA gene has a very high risk of developing neurological disease.

Transmission is autosomal recessive.

The treatment for patients with GD type 3 exhibiting clinically significant non neurological manifestations is enzyme substitution therapy (imiglucerase with marketing authorization (MA) since 1997). It appears to slow progression of the neurological symptoms and is effective against the systemic manifestations.

In the absence of treatment, clinical progression leads to death within a few years.

Visit the Orphanet disease page for more resources.

Last updated: 2/1/2012

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.