Gaucher disease (GD) is a rare lysosomal storage disorder in which a deficiency of the enzyme glucocerebrosidase leads to accumulation of its substrate glucosylceramide. This substrate accumulates in macrophages and these accumulated cells are mainly localized in spleen, liver and bone marrow, causing a range of symptoms.
Background
At present, monitoring of GD is performed with the use of biochemical parameters and imaging of liver, spleen and bone marrow using magnetic resonance imaging (MRI). There is no method available to assess the amount of accumulated cells in the entire body. A new approach in this field is imaging of the amount of iron using whole body magnetic resonance imaging (MRI). It is known that iron is an often seen component in Gauchercells and therefore it is possible that iron could be used as a marker of Gauchercells. Using a whole body MRI iron protocol it can be possible to gain an improved insight in severity and extent of Gaucher disease.
We hypothesize that in patients with GD the whole body MRI iron measurements are a useful tool in determining the distribution and total amount of Gauchercells in the body and can be of use in monitoring disease activity, early detection of complications and treatment decision-making.
Objectives
We propose to investigate the applicability of the whole body MRI protocol in Gaucher disease. We will study the differences in iron levels in different organs between patients and healthy controls and study the effect of treatment on the burden of disease. The measurements will be compared to present-day standard of care monitoring.
Study design
Case-control study. 40 Gaucher patients and their age and sex matched healthy volunteers will undergo the investigational MRI scanning; whole body iron measurement of the abdomen, spine, femora, tibulae, fibulae, humeri, radii and ulnae. We also perform the regular standard-of-care MRI protocol used in Gaucher disease: Dixon QCSI fat fractions of the lumbar spine, assessment of bone marrow burden (BMB) score of femora and MR volumetry of liver and spleen. The Dixon QSCI fat fractions will be determined for tibia and fibula as well in the light of this study.
A subgroup of patients and healthy controls will be scanned twice with the whole set of examinations repeated 1-4 weeks after the baseline scan to study the reproducibility.
A second subgroup of ‘early treatment phase’ patients and their matched healthy controls are asked for a second MRI, one year after the baseline scan.
To study the residual disease activity (that is, disease activity during therapy) in relation to complications we will create subgroups of patients consisting of patients with and without persistent bone disease and patients with and without monoclonal gammopathy and compare their baseline MRI scans.
Venous blood samples will be obtained from all participants at baseline. We check Hb, Ht, MCV, ACE, ferritin, transferrin, total iron, total iron binding capacity, ironsaturation, hepcidin in all participants. In Gaucher patients we also determine the standard ‘Gaucher parameters’; immunoglobulins, light chains, M-protein, chitotriosidase and chitotriosidase mutation status, CCL18/PARC (only in case of chitotriosidase deficiency), glycosphingolipids.
Primary outcomes
The main study parameter is the difference in the measured ironlevels (expressed as R2*, a MRI based value correlating with ironconcentration (µmol/g)) between Gaucherpatients and healthy controls. This new whole body MRI technique will be compared with our standard-of-care parameters of disease.
Start date/expected completion:
Start date: 11-2013
Expected completion: 04-2016
Expected number of patients
40 Gaucher patients and their age and sex matched healthy volunteers
Study type
Case-control study
Contact
M. Regenboog, MD, study coordinator
Dept. of Radiology / Dept. of Endocrinology & Metabolism
Academic Medical Center
Meibergdreef 9
1105 AZ Amsterdam
E m.regenboog@amc.uva.nl