27 April 1998
We are interested in clarifying the pathogenesis of the neuronpathic
type III Gaucher disease (GD). GD is the most prevalent hereditary metabolic
storage disease, and the most common genetic idsorder in individuals of
Ashkenazi Jewish ancestry. GD transmitted in an autosomal recessive manner
is mostly caused by a deficient activity of the enzyme glucocerebrosidase
(GBA). The clinical phenotypes are classified into three groups: non-neuronpathic
(type I, which is the most common variant with an incidence of 1 in 30.000,
acute neuronpathic (Type II) and chronic (subacute) neuronopathic (type
III).
ALthough many different point mutations, some insertions, deletions
and more complex disease alleles due to recombination events with the GBA
pseudogene (GBAP) have been identified, in about 25-35% of all Caucasian
GD patients the
mutation is still unknown.
To get more detailed information of the distribution and frequency of
the mutational pattern in European-non-Jewish, Caucasian GD patients we
have up to now analyzed the entire GBA coding region in 75 non-Jewish GD
patients from
whom 11 suffered fom the chronic neuronpathic GD variant. The enzyme
replacement therapy which is highly effective in patients with type I has
only moderate benefit in patients with type III.
As part of our genetic research project we are lookin for further type III GD patients which are mainly characterized by multifocal myoclonus and generalized seizures, horizontal supranuclear gaze palsy, ataxia, spasticity and in the most cases only moderate herpatosplenomegaly and thrombocytopenis. We have established a sequencing procedure for the complete coding GBA as well as for the Nimann-Pick type C- (NPC1)-gene since Niemann-Pick type C is the major differential diagnosis of GD.
If you have patients with seizures of unclear etiology in combination with a hepatosplenomegaly, ataxia or supranuclear gaze palsy we are offering a genetic analysis for the GBA and NPC1 gene.
We would be grateful also for collaboration with other groups who are aware of type III GD families.