Abstract
Gaucher disease is one of the most common lysosomal storage diseases. Due to the underlying β-glucocerebrosidase enzyme deficiency, there is an accumulation of glucosylceramide (Gb1) and lyso-glucosylsphingosine (lyso-Gb1), as the breakdown thereof is disrupted. Gb1 and lyso-Gb1 accumulate in the lysosomes of the macrophages, known as Gaucher cells, of various organs (liver, lungs, bones, spleen and sometimes central nervous system) where they can cause a variety of symptoms. The clinical presentation is therefore very diverse, but (hepato)splenomegaly (whether or not in combination with thrombocytopenia) is always present. When clinically suspected, the diagnosis can be made by detecting the enzyme activity. In case of abnormal results, genetic analysis follows for the detection of mutations in the GBA1 gene, which is associated with Gaucher disease. A large proportion of patients develop manifestations of the disease in childhood, but are unfortunately diagnosed too late.
With this study we aim to accelerate the diagnostic process by developing an efficient, sensitive and specific screening method based on detection of the biomarker lyso-Gb1 on dried blood (Newborn blood spot cards). Lyso-Gb1 has been shown in previous studies as a sensitive and specific biomarker for Gaucher disease. Liquid Chomatography-Mass Spectrometry (LC-MSMS) will be used for the analysis of the dried blood spots. There is currently 1 other study, the study by I. Motta et al. 2016, which performed a (successful) screening using dried blood. When developing an enzymatic assay on dried blood using the LC-MSMS, we also want to simultaneously look at Niemann-Pick disease type B/ASMD (given the similar clinical presentation). The main goal of this study is the early detection of patients with Gaucher disease so that treatment can also be started on time and any organ damage is prevented/limited. For this purpose, patients between 2 and 18 years old with splenomegaly, and with or without thrombocytopenia, without other known underlying disorders from the pediatric haematological-oncological population (hematology departments of the university hospitals in Belgium / participating hospitals in close collaboration with the 'Belgian Society of Hematology & Oncology") will be recruited. If the patients meet the inclusion/exclusion conditions, they can be included in the screening program if they agree and sign the informed consent. Blood samples (for complete blood count, blood cell morphology, platelet count, enzyme assay of glucocerebrosidase and measurement of lyso-Gb1) and spleen dimensions (measured by MRI or CT) will be collected from all enrolled patients for further data analysis.
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