Abstract
BackgroundThe study aim was to verify the feasibility of a diagnostic algorithm with the evaluation of beta glucocerebrosidase (GBA) activity on dried blood spots (DBS) in screening high-risk Gaucher disease (GD) children in China, and to investigate the GD prevalence in this selected population.MethodsChildren were recruited from 20 departments of pediatrics or children’s hospitals in Shandong Province, China, due to splenomegaly and/or thrombocytopenia associated with one or more of the following creteria: anemia, history of bone pain, monoclonal gammopathy of unknown significance (MGUS), polyclonal gammopathy and splenectomy. GBA activity on DBS was tested, and patients with DBS GBA activity under 30 nmol/h.ml were recalled to assess enzyme assay with gold standard and molecular GBA gene analysis on leukocytes.ResultsA total of 73 children (47 boys and 26 girls) were enrolled in this study. GBA activity DBS < 30 nmol/h.ml was found in 18 (23.7%) children among which four (three boys and one girl) were diagnosed as GD with a median age 1.5 years, and the prevalence in this pediatric population was 5.5% (1.5%~ 13.4%). Three new mutations of GBA found in the four GD patients, L264I, A100Cfs*7 and D399E, have not been reported before.ConclusionsWith evaluation of GBA activity on DBS as a preliminary screening method, the diagnostic algorithm used in this study is appropriate to make early diagnosis for GD patients with mild symptoms or atypical symptoms and avoid diagnosis delay.Trial registrationNot applicable.
Highlights
The study aim was to verify the feasibility of a diagnostic algorithm with the evaluation of beta glucocerebrosidase (GBA) activity on dried blood spots (DBS) in screening high-risk Gaucher disease (GD) children in China, and to investigate the GD prevalence in this selected population
Referring to the algorithm described in the expert consensus on diagnosis and treatment of GD in China (2015) [3], the two enrolment criteria were splenomegaly and/or thrombocytopenia associated with one or more of the following criteria: anemia, history of bone pain, monoclonal gammopathy of unknown significance (MGUS), polyclonal gammopathy and splenectomy
Splenomegaly was detected and conformed by physical examination and/or imaging techniques such as ultrasound, computed tomography or magnetic resonance imaging; thrombocytopenia was defined as the platelet count < 100,000/mm3; and based on the ageadjusted reference value, anemia was defined as hemoglobin (Hb) < 145 g/L for neonates; Hb < 90 g/L for infants aged 1~ 4 month-old; Hb < 100 g/L for infants aged 4~ 6 month-old; Hb < 110 g/L for infants/children aged 6 month-old to 6 year-old; and Hb < 120 g/L for children aged 6~ 14 year-old
Summary
The study aim was to verify the feasibility of a diagnostic algorithm with the evaluation of beta glucocerebrosidase (GBA) activity on dried blood spots (DBS) in screening high-risk Gaucher disease (GD) children in China, and to investigate the GD prevalence in this selected population. The GBA mutation may result in a deficiency of enzyme activity, leading to the accumulation of substrate glucocerebroside in the reticuloendothelial cells of the spleen, liver, bone, lung and even brain, and subsequently causing multiple organ involvement with progressive exacerbation, such as hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological involvement, as well as GD is a panethnic hereditary disease with greatly different incidence in different populations, for instance, about 1/800 in Ashkenazi Jews, while 1/40000 in nonAshkenazi population [1]. The optimal effect with ERT was based on the early diagnosis of GD because some irreversible changes, such as avascular bone necrosis, hepatic, splenic or bone marrow fibrosis, and pulmonary hypertension, may occur in affected organs if the ERT was not timely initiated [6, 7]
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