Consequences of diagnostic delays in type 1 Gaucher disease: The need for greater awareness among Hematologists–Oncologists and an opportunity for early diagnosis and intervention

Abstract

Gaucher disease (GD) is a progressive macrophage lipidosis capable of causing disabling and life-threatening complications. Anecdotal experiences suggest that GD may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy (ERT) with imiglucerase. We conducted surveys of patients and Hematology-Oncology specialists to assess the frequency of diagnostic delays. Additionally, we report a series of patients who suffered diagnostic delays and as a result developed disabilities including potentially life-threatening manifestations of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 48.7 ± 123.6 months. More than two-thirds were evaluated and managed by a Hematologist-Oncologist (Hem-Onc). A global survey of 406 Hem-Oncs found that only 20% considered GD in the differential diagnosis for all of its classic symptoms (cytopenia, hepatosplenomegaly, bone pain); the diagnosis considered most likely included leukemia, lymphoma, and multiple myeloma. To illustrate actual consequences of diagnostic delays, we describe 14 patients with GD who suffered from symptoms for up to 10 years before correct diagnosis. Diagnostic delays led to complications that are preventable or reversible with ERT (i.e., avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, liver pathology). Patients homozygous for N370S mutation in this series were vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur in GD and may result in severe disease manifestations. Our findings suggest that physician education will increase the likelihood of prompt detection of GD and improve its management with ERT with imiglucerase when indicated. Am. J. Hematol. 82:697-701, 2007. V

A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase

“…This benchmark will provide a point of reference for physicians treating GD1 patients who wish to individualize therapy with the goal of optimizing outcomes. A coordinated approach considering a variety of therapeutic goals, rather than an exclusive focus on treating individual symptoms, may result in better long-term outcomes for GD1 patients [9]. The information in this benchmark analysis may assist physicians in choosing the appropriate treatment approach for each patient while considering the potential benefits and the overall safety profile of imiglucerase [22].…”

“…Although there appear to be numerous minimally affected individuals, in particular Ashkenazi Jews, who remain largely asymptomatic throughout life, without effective treatment overtly symptomatic patients with GD1 may suffer from disabling skeletal disease, abdominal pain, bleeding complications and, rarely, infection, liver failure, and severe pulmonary disease [8,9]. In children and adults with diverse presentations of disease, treatment with intravenous macrophage-targeted enzyme replacement therapy (imiglucerase, Cerezyme 1 , Genzyme Corporation) has been shown to abate anemia, thrombocytopenia, and organomegaly and to impede the progression of bone disease [10].…”

A Rare Condition in Haematological Practice – Gaucher Disease

“…28,37 Concerns about safety of treatments may also account for this delay. Enzyme testing diagnosis of Gaucher disease is unequivocal; however, Gaucher disease is rare with a non-specific and heterogeneous manifestations, and minor overt symptomatology at onset, all of which hinders consideration of the disease in differential diagnosis.…”

“…38 Cytopenias and splenomegaly can lead to suspicion of haematological malignancy, especially in the presence of focal splenic lesions. 37 However, concomitant presence of hyperferritinaemia, polyclonal gammopathy, without neutropenia, but together with a more insidious onset may be useful in differentiating from malignancy. 22 Early symptoms of Gaucher disease reflect the haematological characteristics such as splenomegaly, anaemia, thrombocytopenia and bleeding.…”

Ocular Features of Treatable Lysosomal Storage Disorders – Fabry Disease, Mucopolysaccharidoses I, II and VI and Gaucher Disease

“…58 Unfortunately, even in such cases prolonged diagnostic delays occur that may result in even more severe disease manifestations. 59 Chronic (type 3) neuronopathic disease includes several variants. 60 Patients may exhibit prominent neurological abnormalities with relatively mild visceral involvement.…”