Gaucher Disease

This is a severe systemic disease with perinatal lethality in some patients.  The range of clinical heterogeneity is wide, however, and minimally affected adult patients have also been described.  Individuals with nonneuropathic type I lack central nervous system involvement.  They often do have hepatosplenomegaly and pancytopenia with bone marrow involvement which are common to all types.  The latter may be responsible for frequent bone fractures and other orthopedic complications such as vertebral compression.  Thrombocytopenia with bleeding complications contributes to the primary anemia which is also present.  Interstitial lung disease can be seen in type I disease but occurs in less than 5% of patients. This is the most common of the three types. 

Patients with type I Gaucher disease have an increased risk of cancer, especially those of the hematological system.  For example, the risk for multiple myeloma has been estimated to be 37 times higher than in the general population.  There is also evidence of an increased incidence of multiple consecutive cancers in this condition.  Enzyme replacement therapy may reduce the risk of malignancies.

Patient with types II (acute neuronopathic [230900]) and III (subacute neuronopathic [231000]) are more likely to have neurologic disease with bulbar and pyramidal signs and sometimes seizures.  In type II, onset is in infancy and lifespan is about 2 years.   They have hepatosplenomegaly with growth arrest and developmental delays after a few months.  The clinical signs in type III or subacute neuronopathic type the onset is later (2.5 years to adulthood) than in type II and progression of neurologic disease is slower.  Early childhood development may appear normal for several years until abnormal extraocular movements or seizures are observed.  Type III is sometimes called Norrbottnian type.