How I treat Gaucher disease

Abstract

This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. (Blood. 2011;118(6): 1463-1471) IntroductionThe purpose of this review is to present a cohesive approach to treating patients with Gaucher disease (GD). As can be appreciated, the spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer, in providing adequate treatment for all symptomatic patients with GD. As a treating physician dedicated to GD even before the era of enzyme replacement therapy (ERT), my mandate and inspiration has always been to provide the best therapy with the least malfeasance. Description of GDGD is one of the most common glycolipid storage disorders, caused by an inherited deficiency of the lysosomal enzyme ␤-glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. 1 Accordingly, key disease features are related to splenomegaly with hypersplenism, hepatomegaly, and bone involvement. Although a single-gene disorder, phenotypic expression is extremely variable, ranging from totally asymptomatic (only detectable by DNA analysis or enzyme deficiency) to a lethal newborn form with hydrops fetalis and ichthyosis. Many manifestations, some notuncommon and others very rare, cannot be explained by storage per se; examples include immunologic abnormalities, increased prevalence of certain malignancies with relative paucity of ...

Clinical utility of different bone marrow examination methods in the diagnosis of adults with sporadic Gaucher disease type 1

“…Currently, if GD is suspected based on morphological findings, such as the presence of Gaucher cells in tissue specimens, the gold standard diagnosis requires confirmation by appropriate enzymatic and genetic assays. [1][2][3][4][5]15 The choice of the bone marrow examination method is often random, influenced by many different factors related both to the patient (eg, concomitant symptoms, comorbidities, local conditions at the examination site, etc) and the physician (eg, local routines, personal experience, etc). TB has been introduced into routine hematological diagnostic workup relatively recently in many countries (approximately the last 20 years), at the time when bone marrow examination was no longer recommended for the sole purpose of GD diagnosis.…”

“…Thrombocytopenia, anemia, splenomegaly, hepatomegaly, and bone manifestations are the most typical signs of the most prevalent form of GD, GD1. [1][2][3][4][5]10 The presence of central nervous system disease, in addition to the above symptoms, is a hallmark of GD type 2 and type 3. 11 GD is well known for its striking phenotypic diversity, which can complicate diagnosis.…”

“…1,2,15 In the non-Ashkenazi populations, GD is markedly less frequent (1 in 40,000-200,000 people) than hematologic malignancies. 1 In milder forms of GD1, when the clinical picture is scant, and in the absence of any known affected family member, GD remains a diagnostic challenge. It is often not included in the differential diagnosis of thrombocytopenia even by experienced hematologists.…”

“…10-13 Although according to the European Union definition, GD belongs to so called rare diseases (ie, affecting less than 1 persons/2000 inhabitants), 14 the diagnosis of GD1 should be considered in any patient who presents with a long clinical history of splenomegaly and thrombocytopenia, in children with acute or chronic bone pain, growth retardation, and in individuals with nontraumatic avascular necrosis of a large joint at any age. 1,10 In patients of Ashkenazi Jewish ancestry, the frequency of GD is 1 in 800, while hematologic malignancies are much less frequent (1 in 2500 people).…”

“…1,22 ERT has the potential to positively affect all domains of GD1 (ie, hematological, visceral, and skeletal). 23,24 Since 1991, GD has become a model for the development of ERT in other lysosomal storage disorders.…”