Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient 
activity of the enzyme glucocerebrosidase. GD is classically divided into three 
major phenotypes. The most prevailing form is type 1, which presents with 
variable hepatosplenomegaly, cytopenia, and/or bone disease. In adult patients 
with mild manifestations, progress of disease might be slow or even absent. As a 
consequence, treatment with intravenous enzyme replacement or substrate 
reduction is not always necessary. In the Netherlands, the follow-up of GD 
patients is centralized, which allows detailed investigation of untreated 
patients. A retrospective study was conducted in 18 type 1 GD patients, (2 
teenagers: 15 and 16 years of age at first visit) who were not treated for at 
least one year. The chitotriosidase activity, platelet count, hemoglobin level, 
lumbar bone marrow fat content measured with quantitative chemical shift imaging 
(QCSI), liver ratio (ml/kg body weight), and spleen volume were recorded. 
Criteria were developed to score regression, stability or progression of 
disease. During a mean follow up of 4.5 years (range 1.1-12.2) seven patients 
(39%) showed spontaneous regression of GD. Eight patients (44%) were stable. Two 
patients had progressive disease, solely based upon a sustained increase in 
chitotriosidase activity. A pediatric patient had an increase in splenomegaly 
but an improvement in bone marrow fat fraction, probably due to aging. Nine 
patients fulfilled the local criteria to start treatment at first visit, of whom 
six started treatment within 1.1 to 6.8 years. The other three refused therapy, 
but nevertheless showed stability or even regression of the disease during a 
follow up of 4.6, 9.5 and 11.4 years respectively. None of the parameters was 
predictive of progression or regression of disease. In conclusion, GD in adults 
can, in some cases, regress spontaneously. No parameters for accurately 
predicting future disease course exist.