Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy

Itzchaki, Menachem; Lebel, Ehud; Dweck, Altoon; Patlas, Michael N.; Hadas‐Halpern, Irith; Zimran, Ari; Elstein, Deborah

doi:10.1080/00016470410004003

Cited by 44 publications

(27 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This bias has been proven to be wrong, and patients with GD should be candidates for arthroplasty on the basis of criteria of pain and poor function just like others. [38][39][40][41][42][43] Moreover, orthopedic surgery is still a mainstay of GD management for patients who have developed irreversible joint damage before ERT and patients with skeletal complications despite ERT. 43 I recommend a team approach before surgery particularly for patients with bleeding tendencies.…”

Section: Surgical Procedures: Orthopedic Surgeriesmentioning

confidence: 99%

See 1 more Smart Citation

How I treat Gaucher disease

Zimran

2011

Blood

Self Cite

147

135

View full text Add to dashboard Cite

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 ...

show abstract

Section: Surgical Procedures: Orthopedic Surgeriesmentioning

confidence: 99%

“…37,38 Patients' expectations about improvement in disease-specific parameters with therapeutic interventions are an important aspect of routine visits. Patients may or may not have realistic ideas of what disease-specific therapy may accomplish.…”

Section: Imaging Modalitiesmentioning

confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

Self Cite

147

135

View full text Add to dashboard Cite

show abstract

“…As such, its primary manifestations are often due to marrow replacement and ensuing hematopoietic effects or bony deformity or fracture. Type II and III Gaucher disease both feature neurologic involvement [1,2]. Type III carries a less favorable prognosis and progresses more rapidly than type II.…”

Section: Discussionmentioning

confidence: 97%

“…The disease is characterized by a deficiency of beta-glucocerebrosidase, which in turn leads to accumulation of glucocerebrosides (specifically glucosylceramide). Glucocerebroside-laden macrophages known as Gaucher cells typically accumulate in the liver, spleen, bone marrow, lymph nodes, brain, and lung [1][2][3][4][5][6][7][8][9]. Bone marrow involvement with Gaucher disease is particularly common, being a major complication in up to 80 % of affected patients and can result in anemia, coagulopathy, osteonecrosis, bony remodeling, and fracture [3,4].…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Extraosseous Gaucher cell deposition without adjacent bone involvement

2014

View full text Add to dashboard Cite

Extraosseous Gaucher cell deposits are a rare complication of Gaucher disease that can mimic malignancy. We describe a case of Gaucher cell deposition in the subcutaneous soft tissues overlying the lower thoracic spine in an 18-year-old woman with known type III Gaucher disease. This case is unique in the literature because this subcutaneous Gaucher mass was not associated with extension from underlying bone involvement or clear lymph node origin. It demonstrated no discernible continuity with the adjacent thoracic spinous processes, the cortices of which appeared intact. Although patients with Gaucher disease are at increased risk of malignancy, Gaucher cell deposition should remain a differential consideration for soft tissue masses with or without adjacent bone involvement in patients with known Gaucher disease.

show abstract

Recent Therapeutic Advancements for Gaucher Disease

Pradhan,

Manna,

Pragya

et al. 2024

Advanced Therapeutics

View full text Add to dashboard Cite

Gaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits a range of clinical manifestations, each with unique symptoms and severity levels. This review explores the genetic foundations of GD, highlighting the significance of Glucocerebrosidase (GCase) deficiency, resulting in the skeletal complications associated with GD, such as osteonecrosis, fractures, and bone pain, all of which significantly negatively influence the quality of life for patients. Over 700 mutations in the GBA1 gene are found to cause variations in gene expression in GD, indicating the disease's complexity and the need for continued research. Early diagnosis and prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, genetic testing, and clinical symptoms. Treatment strategies like enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have advanced, but issues like high costs and invasiveness still exist. This review focuses on novel therapeutic approaches that show promise in treating GD, including gene and cell‐based therapies, pharmacological chaperone therapy (PCT), and drug delivery via nanoparticles. Finally, discussions on current clinical trials, limitations of the advanced therapies, and future scope are summarized.

show abstract

Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy

Cited by 44 publications

References 45 publications

How I treat Gaucher disease

How I treat Gaucher disease

Extraosseous Gaucher cell deposition without adjacent bone involvement

Recent Therapeutic Advancements for Gaucher Disease

Contact Info

Product

Resources

About