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Similarities and differences between Gaucher disease and acid sphingomyelinase deficiency: An algorithm to support the diagnosis

  • Maria Domenica Cappellini
    Correspondence
    Corresponding author at: Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano.
    Affiliations
    Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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  • Irene Motta
    Affiliations
    Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
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  • Antonio Barbato
    Affiliations
    Department of Clinical Medicine and Surgery, Federico II University of Naples Medical School, Naples, Italy
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  • Gaetano Giuffrida
    Affiliations
    Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare, Division of Haematology, A.O.U Policlinico-S. Marco, Università degli studi di Catania, Catania, Italy
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  • Raffaele Manna
    Affiliations
    Department of Internal Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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  • Author Footnotes
    1 These authors equally contributed to this work.
    Francesca Carubbi
    Footnotes
    1 These authors equally contributed to this work.
    Affiliations
    Metabolic Medicine Unit, Azienda Ospedaliero Universitaria Modena, University of Modena and Reggio Emilia, Modena, Italy
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  • Author Footnotes
    1 These authors equally contributed to this work.
    Fiorina Giona
    Footnotes
    1 These authors equally contributed to this work.
    Affiliations
    Department of Translational and Precision Medicine, Sapienza University of Rome, AOU Policlinico Umberto I, Rome, Italy
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  • Author Footnotes
    1 These authors equally contributed to this work.
Published:November 26, 2022DOI:https://doi.org/10.1016/j.ejim.2022.11.028

      Highlights

      • Gaucher disease type 1(GD1) and acid sphingomyelinase deficiency (ASMD) overlap for several signs or symptoms.
      • Splenomegaly is present in approximately 90% of the patients in both conditions.
      • Both diseases are underdiagnosed, especially ASMD.
      • We provide an algorithm for both conditions to support physicians, including primary care providers, internists, and specialists, to suspect and differentiate GD1 and ASMD.

      Abstract

      Lysosomal storage disorders are a group of inborn errors of metabolism due to defects in proteins crucial for lysosomal function. Gaucher disease is the most common autosomal recessive lysosomal storage disorder due to mutations in the GBA1 gene, resulting in the lysosomal deficiency of glucocerebrosidase activity. Gaucher disease is characterized by the toxic accumulation of glucosylceramide in the reticuloendothelial system. Acid sphingomyelinase deficiency (ASMD), previously known as Niemann Pick A/B disease, is also an autosomal recessive lysosomal storage disorder due to mutations in the SMPD1 gene, which result in acid sphingomyelinase deficiency and the accumulation of sphingomyelin in mononuclear phagocytic system and hepatocytes. The phenotypic expression of Gaucher disease type 1 (GD1), the most common type, and chronic visceral ASMD may overlap for several signs or symptoms. Splenomegaly is detectable in approximately 90% of the patients in both conditions; however, since GD1 is more frequent than ASMD, clinicians are more prone to suspect it, often neglecting the diagnosis of ASMD.
      Based on previous experience, a group of experts in the clinical and laboratory diagnosis, management, and treatment of lysosomal storage disorders developed an algorithm for both GD1 and ASMD to support physicians, including primary care providers, internists, and specialists (e.g., hepatologists, hematologists, and pulmonologists) to suspect and differentiate GD1 and ASMD and to provide the appropriate referral.

      Keywords

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