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<p>Gaucher disease (GD) exemplifies how a single genetic mutation can give rise to a complex multisystem disorder with profound hematological implications. Central to its pathophysiology is the lysosomal accumulation of glucosylceramide due to deficient glucocerebrosidase activity, together with abnormal folding and trafficking of the enzyme that induce endoplasmic reticulum stress and cellular dysfunction. These processes disrupt reticuloendothelial homeostasis and interfere with hematopoiesis. As a consequence, macrophage activation and chronic inflammation contribute to the cytopenias, splenomegaly, and hyperferritinemia that frequently lead patients to hematological evaluation. Despite significant therapeutic advances, GD remains under-recognized in routine hematology practice, often resulting in diagnostic delays and suboptimal management. The introduction of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) has transformed the treatment landscape by targeting the underlying metabolic defect and mitigating systemic inflammation. Early diagnosis and timely initiation of therapy are essential to prevent irreversible organ damage and improve long-term outcomes. This review provides an integrated hematological perspective on GD, highlighting its pathophysiological basis, clinical manifestations, and diagnostic challenges through a representative real-world clinical case. By linking biological mechanisms to practical diagnostic reasoning, the review aims to facilitate earlier recognition of GD in hematology practice and ultimately improve patient outcomes.</p>

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Gaucher disease: the hematologist’s perspective of a multisystemic disorder

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Alessandro Costa,
  • Olga Mulas,
  • Giovanni Caocci

摘要

Gaucher disease (GD) exemplifies how a single genetic mutation can give rise to a complex multisystem disorder with profound hematological implications. Central to its pathophysiology is the lysosomal accumulation of glucosylceramide due to deficient glucocerebrosidase activity, together with abnormal folding and trafficking of the enzyme that induce endoplasmic reticulum stress and cellular dysfunction. These processes disrupt reticuloendothelial homeostasis and interfere with hematopoiesis. As a consequence, macrophage activation and chronic inflammation contribute to the cytopenias, splenomegaly, and hyperferritinemia that frequently lead patients to hematological evaluation. Despite significant therapeutic advances, GD remains under-recognized in routine hematology practice, often resulting in diagnostic delays and suboptimal management. The introduction of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) has transformed the treatment landscape by targeting the underlying metabolic defect and mitigating systemic inflammation. Early diagnosis and timely initiation of therapy are essential to prevent irreversible organ damage and improve long-term outcomes. This review provides an integrated hematological perspective on GD, highlighting its pathophysiological basis, clinical manifestations, and diagnostic challenges through a representative real-world clinical case. By linking biological mechanisms to practical diagnostic reasoning, the review aims to facilitate earlier recognition of GD in hematology practice and ultimately improve patient outcomes.