Gaucher disease type 1
Gaucher Disease type 1 is the Chronic non-neurological form of Gaucher Disease (a lysosomal storage disorder caused by a deficiency in glucocerebrosidase) characterized by organomegaly, Bone involvement and cytopenia.
Additional InformationGaucher Disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase. Three main types of Gaucher Disease have been defined, among which Gaucher Disease type 1 represents 95% of all cases. The prevalence of the type 1 form in the general population is around 1 in 100,000. Gaucher Disease type 1 is characterised by the absence of specific neurological anomalies. The Clinical manifestations are very heterogeneous and asymptomatic forms have sometimes been reported. The age at Diagnosis varies between 0 and 90 years of age but half of the patients are under the age of 10 at the time of diagnosis. The Clinical picture is characterised by the association of frequent asthenia, growth retardation or delayed puberty, and splenomegaly (95% of patients) that may be complicated by splenic infarctions that sometimes become superinfected. Hepatomegaly is reported in more than 80% of patients. Progression towards Fibrosis then Cirrhosis is rare. Ultrasound and magnetic resonance Imaging (MRI) provide valuable Information during the initial evaluation and during follow-up. Bone disease is present in 80% of patients and may be disabling. The Bone anomalies 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. MRI can be used to identify mildly symptomatic Bone anomalies. Osteodensitometry allows determination of the degree 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 Hypertension rather than identification of specific Cardiac anomalies. Several biochemical anomalies are also present. Pancytopaenia is frequent and is associated with various degrees of thrombocytopaenia (sometimes severe), anaemia and, more rarely, leukoneutropaenia. Polyclonal hypergammaglobulinaemia is often present and is sometimes complicated 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. Genotyping may be of prognostic value in rare cases: individuals carrying the N370S mutation are not at risk of developing neurological disease, whereas homozygous carriers of L444P mutations have a very High risk of developing neurological manifestations. At present, there are two specific treatments for Gaucher disease. Enzyme substitution Therapy remains the treatment of choice: in 1997, imiglucerase obtained EU marketing authorisation as an Orphan Drug for treatment of patients with Gaucher Disease type I. Substrate reduction Therapy provides an alternative second-line treatment. Bisphosphonates may be recommended to Prevent bone complications.
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