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Hematologists are frequently involved in the diagnostic pathway of Gaucher disease type 1 (GD1) patients since they present several hematological signs. However, GD1 is mainly underdiagnosed because of a lack of awareness. In this multicenter study, we combine the use of a diagnostic algorithm with a simple test (β-glucosidase activity on Dried Blood Spot) in order to facilitate the diagnosis in a population presenting to the hematologist with splenomegaly and/or thrombocytopenia associated with other hematological signs. In this high-risk population, the prevalence of GD1 is 3.3%. We propose an equation that predicts the probability of having GD1 according to three parameters that are routinely evaluated: platelet count, ferritin, and transferrin saturation.

Background and Aims: Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD., Methods: Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min., Results: Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024)., Conclusions: Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We aimed at: assessing the prevalence of significant liver fibrosis in a cohort of patients with type 1 GD; identifying its predictors among GD-related variables, enzyme replacement therapy (ERT) and metabolic features., Methods: 37 adult type 1 GD patients from two Italian academic referral centers were prospectively submitted to vibration controlled transient elastography (Fibroscan®); significant fibrosis was defined as liver stiffness ≥7 kPa., Results: Median liver stiffness was 4.6 [3-15.1] kPa and 7 patients (19%) had significant fibrosis. Significant fibrosis was associated with splenectomy (p = .046) and with scores (DS3: p = .002; SSI: p = .026) and biomarkers (ACE: p = .016; HDL cholesterol: p = .004) of GD severity. Length of ERT was significantly lower in GD patients with significant fibrosis. In the subgroup of 29 patients who were on stable ERT for at least 24 months, further to splenectomy, GD severity and non-N370S GBA1 genotypes, also diastolic blood pressure, BMI and the number of metabolic syndrome (MetS) components emerged as factors significantly associated with significant fibrosis., Conclusions: Significant fibrosis is present in a remarkable proportion of adult type 1 GD patients. Splenectomy, GD severity and GBA1 genotypes are major GD-related predictors of liver fibrosis. Length of ERT is inversely correlated with liver disease in GD patients, suggesting a beneficial effect of ERT on liver fibrosis. However, GD patients on stable ERT should be monitored for metabolic complications, since MetS features may enhance liver disease progression despite optimal GD control., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Type 1 Gaucher disease (GD1) is the most common lysosomal disorder, characterized by the accumulation of beta-glucocerebroside into the macrophages of several organs. Cardiac involvement is rare and referred to as restrictive cardiomyopathy, pulmonary hypertension, and calcifications of the valves and the aortic arch., Aim: To assess the cardiovascular status by cardiac magnetic resonance, including evaluation of tissue characterization, in GD1 patients., Methods: Nine GD1 patients were recruited at the Tertiary Care Centre for Rare Diseases at Ca' Granda Foundation IRCCS Hospital, Milan. The patients' records were available for a mean time of 6 ± 3 years. Medical history of cardiac disease and cardiovascular risk factors were surveyed by direct interview. Patients were scanned with a 1.5 Avanto Siemens using a comprehensive cardiovascular evaluation protocol, including morphologic and functional sequences with gadolinium contrast media, to assess early and late enhancement (late gadolinium enhancement). Echocardiography was performed to study the cardiac morphology and function, including the measurement of pulmonary pressure., Results: Three patients showed left atrial enlargement, one patient showed moderate aortic stenosis in bicuspid valve with mild aortic dilatation, and one patient showed moderate mitral regurgitation. No evidence of myocardial late gadolinium enhancement was detected after gadolinium contrast media. Seven patients received enzyme replacement therapy for a median of 1 year, and two patients were evaluated at diagnosis., Conclusion: Although cardiac disease in Gaucher disease is considered rare and associated with particular genotypes, we have found two valvular diseases and mild left atrial enlargement in three out of nine patients. Further studies to evaluate the prognostic value of these findings are warranted.

Objectives: Gaucher disease (GD) diagnosis relies on the demonstration of deficient β-D-glucosidase (GBA) activity in cellular homogenates. Diagnosis process, however, can be delayed as (i) some GD symptoms are non-specific; and (ii) diagnostic tests are performed in specialized laboratories. These difficulties negatively impact on timely access of patients to therapy. GBA assay in dried blood spots (DBS) represents a method facilitating early identification of patients who will be finally diagnosed with gold standard assay of nucleated cells. Aim of this study is to investigate the DBS analytical performance compared with gold standard method., Design & Methods: A cross-sectional study started by comparing data of 50 DBS and 50 homogenate samples from the same subjects (25 known-GD and 25 controls). The subsequent phase examined 443 DBS samples. Along with these, 73 blood samples were sent for leukocyte separation and/or EBV-lymphoblast cell lines, and 1 skin biopsy for fibroblast cell lines. Overall the study included a total of 493 subjects., Results: While the results from this first validation group did not yield false positive/negative values, when the analysis was extended to 443 DBS, 14.4% (64 samples) of positive results was yielded. Among these, only 15 were confirmed as GD values with gold standard test. In addition, a thorough examination of some clinical data also revealed 2 false negative results which were confirmed by both enzymatic and molecular analyses., Conclusions: DBS test could be useful as screening method although with cautions, whereas the standardized GBA assay should remain the gold standard for laboratory diagnosis of Gaucher disease., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Gaucher disease (GD), the most common inherited lysosomal storage disorder, is a multiorgan disease due to an autosomal recessive defect of the gene encoding glucocerebrosidase enzyme, responsible for the accumulation of glucosylceramide (glucocerebroside) into reticuloendothelial cells, particularly in the liver, spleen and bone marrow. GD is a clinically heterogeneous disorder and it is conventionally classified in type 1 (non-neuronopathic disease), types 2 and 3 (acute and chronic neuronopathic disease, respectively). Features of clinical presentation and organ involvement as well as age, at presentation are highly variable among affected patients. Splenomegaly and/or thrombocytopenia are the most common presenting features either as incidental findings during routine blood count or physical examination. Other possible clinical manifestations can be hepatomegaly with abnormal liver function tests, bone pain often associated with skeletal complications (pathological fractures, avascular necrosis, osteopenia), pulmonary hypertension and, in neuronopathic forms, neurological manifestations (dysfunction of eye motility, mild mental retardation, behavioural difficulties, choreoathetosis and cramp attacks). For all these reasons GD diagnosis is often a real challenge for internists. In the presence of clinical suspicion of GD, the diagnosis has to be confirmed measuring the betaglucocerebrosidase activity in the peripheral leukocytes and by molecular analysis. Each patient needs an accurate initial multisystemic assessment, staging the damage of all the possible organs involved, and the burden of the disease, followed by regular followup. The correct and early diagnosis permits to treat patients properly, avoiding the complications of the disease., (© 2013.)