{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:18:51Z","timestamp":1792095531166,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis. For this reason, in patients with an initial clinical suspicion of Gaucher disease, we aimed to carry out a parallel screening of acid sphingomyelinase and glucocerebrosidase. Methods: Peripheral blood samples of 627 patients were collected, and enzymatic activity analysis was performed on both glucocerebrosidase and acid sphingomyelinase. The specific gene was studied in samples with null or reduced enzymatic activity. Specific molecular biomarkers helped to achieve the correct diagnosis. Results: In 98.7% of patients, normal values of glucocerebrosidase activity excluded Gaucher disease. In 8 of 627 patients (1.3%), the glucocerebrosidase enzymatic activity assay was below the normal range, so genetic GBA1 analysis confirmed the enzymatic defect. Three patients (0.5%) had normal glucocerebrosidase activity, so they were not affected by Gaucher disease, and showed decreased acid sphingomyelinase activity. SMPD1 gene mutations responsible for Acid Sphingomyelinase Deficiency were found. The levels of specific biomarkers found in these patients further strengthened the genetic data. Conclusions: Our results suggest that in the presence of typical signs and symptoms of Gaucher disease, Acid Sphingomyelinase Deficiency should be considered. For this reason, the presence of hepatosplenomegaly, thrombocytopenia, leukocytopenia, and anemia should alert clinicians to analyze both enzymes by a combined screening. Today, enzyme replacement therapy is available for the treatment of both pathologies; therefore, prompt diagnosis is essential for patients to start accurate treatment and to avoid diagnostic delay.<\/jats:p>","DOI":"10.3390\/jcm13051487","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T03:03:20Z","timestamp":1709607800000},"page":"1487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gaucher Disease or Acid Sphingomyelinase Deficiency? The Importance of Differential Diagnosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Miriam","family":"Giacomarra","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-7030","authenticated-orcid":false,"given":"Paolo","family":"Colomba","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Francofonte","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcomaria","family":"Zora","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-5187","authenticated-orcid":false,"given":"Giovanni","family":"Caocci","sequence":"additional","affiliation":[{"name":"Ematologia e Centro Trapianto di Midollo Osseo, Ospedale Businco, Via Jenner, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Diomede","sequence":"additional","affiliation":[{"name":"U.O.C. Ematologia e Trapianto, Ospedale \u201cMons. R. Dimiccoli\u201d, Viale Ippocrate 15, 70051 Barletta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-3338","authenticated-orcid":false,"given":"Gaetano","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Divisione Clinicizzata di Ematologia Sezione Trapianto di Midollo Osseo, Policlinico Vittorio Emanuele-Presidio Ospedaliero Ferrarotto, Via Citelli 6, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fiori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vittore Buzzi Children\u2019s Hospital, University of Milan, Via Castevetro 32, 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4875-6179","authenticated-orcid":false,"given":"Chiara","family":"Montanari","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan, Via Giovanni Battista Grassi 74, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9433-026X","authenticated-orcid":false,"given":"Annamaria","family":"Sapuppo","sequence":"additional","affiliation":[{"name":"Regional Referral Centre for Inborn Errors Metabolism, Pediatric Clinic, Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Scortechini","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero Universitaria delle Marche, Clinica Ematologica, Via Conca 71, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5147-4367","authenticated-orcid":false,"given":"Nicola","family":"Vitturi","sequence":"additional","affiliation":[{"name":"Department of Medicine-DIMED, Division of Metabolic Diseases, University Hospital, Via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Duro","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Zizzo","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., and Brassier, A. 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