type 3 Gaucher's disease
Last edited 02/2019
Gaucher's disease type 3 is an autosomal recessive disorder characterized by reduced glucocerebrosidase activity.
Clinically it is intermediate between types 1 and 2, where splenomegaly and bone involvement are the dominant clinical features, and type 2 Gaucher disease, where central nervous system dysfunction, convulsions, and progressive mental deterioration dominate.
Other organs such as the liver, spleen and lymph nodes may be involved.
| Type 3 | |
| Phenotype |
Accounts for 4% of GD cases. Typically infantile-childhood onset; sub-acute and slowly progressive may result in death during the second decade although some have survived to their 4th decade |
| Visceral symptoms | Hepatomegaly, splenomegaly and interstitial lung disease |
| Hematopoietic symptoms | Anaemia and thrombocytopenia |
| Orthopaedic symptoms | Bony pain crisis, osteopenia, aseptic necrosis of femoral head, bony lytic lesions, bony infarctions and pathological fractures |
| Neurologic symptoms | Oculomotor apraxia, myoclonic epilepsy, generalized tonic-clonic seizures, and cognitive impairment |
The development of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have made GD treatable with the exception of the neurological deterioration associated with types 2 and 3
- ERT aims to replace the defective or missing enzyme with a functional protein that is infused into the bloodstream and taken up into cellular lysosomes
- ERT targets the underlying metabolic deficit rather than providing symptomatic management
- SRT targets the failure of the lysosomal metabolic pathway by inhibiting the production of glucosylceramide and thereby reducing its accumulation in the lysosomes and the likelihood of subsequent multi organ dysfunction