Gaucher disease (MIM 230800) is an autosomal recessive condition caused by a deficiency of the lysosomal enzyme beta-glucocerebrosidase (GBA) and the resultant accumulation of its undegraded substrate, glucosylceramide, in the lysosomes. Biochemical enzyme analysis confirms a clinical diagnosis in affected individuals. The disease can be broadly divided into three clinical forms on the basis of the absence (type I) or presence (types II and III) of primary CNS involvement although there is actually likely to be a clinical continuum. Type II is considered to be the most severe form and type I the least severe. All forms are characterised by hepatosplenomegaly and anaemia with bone involvement common in types I and III. Treatment involves bone marrow transplantation or enzyme replacement therapy. Type I is the most prevalent form and is particularly common in the Ashkenazi Jewish population with an incidence of ~1/855 individuals. Type I shows a broad spectrum of severity ranging from severely affected individuals to asymptomatic, presenting in childhood or adulthood. Types II and III are more rare. All three subtypes are caused by mutations in the GBA gene; the phenotypic heterogeneity correlates to some extent with the different nature of the mutations identified. The GBA gene (1q21) comprises 12 exons. Although many novel mutations are known, there are �common� mutations within the gene, particularly in the Ashkenazi Jewish population.
Also known as
glucocerebrosidase deficiency; GBA deficiency; acid beta-glucosidase deficiency; nonneuronopathic Gaucher disease type I; acute neuronopathic type II; subacute neuronopathic type III
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Clinically affected patients should have their diagnosis confirmed by biochemical analysis; such patients may then be referred for mutation analysis. Carrier testing can be offered to adult relatives of affected patients once a disease causing mutation has been identified. Testing is offered for the following recurrent GBA mutations which account for ~86% mutations in the Ashkenazi population and 70% of mutations in the Non Jewish UK population. Analysis is carried out by PCR & restriction enzyme digest, ARMS PCR and nested PCR analysis: p.Asn409Ser, p.Leu483Pro, p.Arg502Cys, p.Asp448His, c.84dupG, c.(1263_1319)del55 and c.115+1G>A.
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Great Ormond Street Hospital NE Thames Regional Genetics Service Laboratories
Great Ormond Street Hospital for Children
37 Queen Square
1ml EDTA neonates, 5ml EDTA adults
Disease / group
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Prenatals must be arranged in advance, through a Clinical Genetics department if possible. Amniotic fluid or CV samples should be sent to Cytogenetics for dissecting and culturing, with instructions to forward the sample to the Regional Molecular Genetics laboratory for analysis