Summary
Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase. Three main types of Gaucher disease have been described. Gaucher disease type 3 (also known as the juvenile or subacute neurological form) is rare (5% of patients) and is characterised by a later onset and more progressive neurological disease than that seen in Gaucher disease type 2. As in Gaucher disease type 1, the clinical manifestations are very heterogeneous. In some patients the systemic disease is less severe, with ophthalmoplegia as the only neurological symptom. However, various neurological signs (supranuclear horizontal ophthalmoplegia, progressive myoclonic epilepsy, cerebellar ataxia, spasticity and dementia) may be present in more severe cases. Gaucher disease type 3, like type 1, 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, osteopaenia (which sometimes leads to pathological fractures or vertebral compression), bone infarctions or even aseptic osteonecrosis. Standard radiography can be used to search for complications. In addition, 99mTc-bone scintigraphy allows detection of lesions throughout the entire skeleton. Magnetic resonance imaging (MRI) can be used to identify mildly symptomatic bone anomalies. Osteodensitometry allows determination of the degree of osteopaenia of the spinal column and femoral neck. Involvement of other organs is less common but pulmonary anomalies (which are rarely symptomatic), and renal and cardiac defects have been reported. Cardiac ultrasound is required but is used for the detection of pulmonary arterial tension rather than identification of specific cardiac anomalies. Pancytopaenia is frequent and is associated with various degrees of thrombocytopaenia (sometimes severe), anaemia and, more rarely, leukoneutropaenia. Polyclonal hypergammaglobulinaemia is sometimes compounded by monoclonal gammapathy. An increase in biological markers - such as chitotriosidase (an angiotensin converting enzyme), ferritin and tartrate-resistant acid phosphatase (TRAP) - is also observed and is useful both for the initial diagnosis and during follow-up (with or without treatment). Gaucher disease is transmitted as an autosomal recessive trait and is caused by mutations in the GBA gene (1q21). Diagnosis can be confirmed by demonstration of a deficit in glucocerebrosidase activity. Prenatal biochemical diagnosis may be proposed for parents who have already had a child with Gaucher disease type 3 and can be carried out by measuring enzyme activity in chorionic villus samples at 10-12 weeks of amenorrhea or in amniocytes towards 16 weeks of amenorrhea. In 1997, enzyme substitution therapy using the analogue imiglucerase obtained EU marketing authorisation as an Orphan drug for treatment of patients with type 3 Gaucher disease who exhibit clinically significant nonneurological manifestations of the disease. Treatment 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. *Authors: Drs T. Billette, J. Stirnemann, and N. Belmatoug (October 2006)*.
