Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD; see this term). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.
The annual incidence of GD in the general population is around 1/60,000 and the prevalence is approximately 1/100,000. GD type 2 is very rare, with an incidence of approximately 5% of all GD patients and has a prevalence of virtually zero, taking into account its severity and early death.
The disease usually presents in infants aged 3 to 6 months with systemic manifestations of hepatosplenomegaly and an early onset and severe neurological syndrome. The first signs are oculomotor paralysis or bilateral fixed strabismus associated with bulbar signs, in particular severe swallowing difficulties, progressive spasticity and dystonic movements. Seizures occur later and manifest as myoclonic epilepsy that is refractory to treatment with antiepileptics.
GD type 2 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, of the spleen and the bone marrow (Gaucher cells).
A definite diagnosis requires the demonstration of a deficit in the enzymatic activity of glucocerebrosidase.
Biochemical prenatal diagnosis can be proposed to couples who have already had a child with GD type 2. It can be carried out by measuring the enzyme activity in chorionic villus samples at 10-12 weeks of pregnancy or in amniocytes in culture towards 16 weeks of pregnancy.
Transmission is autosomal recessive.
The treatment does not seem to have an effect on neurological manifestations and is therefore not indicated for patients with GD type 2.
Prognosis is poor with most patients dying before the age of 2.
Last update: February 2012
- Dr Nadia BELMATOUG
- Dr Jérôme STIRNEMANN