Gaucher Disease in Bone: From Pathophysiology to Practice

Hughes, Derralynn; Mikosch, Peter; Belmatoug, Nadia; Carubbi, Francesca; Cox, Timothy M.; Göker-Alpan, Özlem; Kindmark, Andreas; Mistry, PK; Poll, L. W.; Weinreb, Neal J.; Deegan, Patrick

doi:10.1002/jbmr.3734

Cited by 129 publications

(130 citation statements)

References 115 publications

(172 reference statements)

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“…Two observations, already accepted in Gaucher research, were also confirmed in this machine-learning study: first, the fact that spleen-removal patients have a higher risk of presenting more serious and extensive bone disease; second, our observation that almost all patients with new bone crisis – despite having received long-term ERT – had previous bone lesions, which remind us that the most feared complication in GD1 are not solved merely by starting ERT. These two facts confirm previous reports and provide validity of our analysis [ 42 , 45 – 47 ]. In addition, genotypes different from homozygous NM_000175.…”

Section: Discussionsupporting

confidence: 93%

“…This study is the first attempt to establish a correlation network among different biochemical and clinical characteristics in a national-base cohort. We have aimed to analyse diagnostic data and to relate them with long-term complications as bone crises, development of neoplasia or PD, which are the most common and disabling complications [ 41 – 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is a priority to identify accurate risk factors of bone crisis to improve treatment dosage and to avoid this complication. The standard biomarkers related to GD (ChT activity, CCL18/PARC and GluSph concentrations) have been discarded as risk factors for bone complication [ 50 , 51 ] even though their concentration will be increased during bone crisis, due to the acute inflammatory event [ 45 , 49 ]. This reminds us of the importance to continue searching for other biomarkers.…”

Section: Discussionmentioning

confidence: 99%

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Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

Andrade‐Campos

Frutos

Cebolla

et al. 2020

Orphanet J Rare Dis

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Background Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p = 0.005); serum levels of IgA, delayed age at start therapy (> 9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (> 1750 mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

Andrade‐Campos

Frutos

Cebolla

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…This study is the rst attempt to establish a correlation network among different biochemical and clinical characteristics in a national-base cohort. We have aimed to analyse diagnostic data and to relate them with long-term complications as bone crises, development of neoplasia or PD, which are the most common and disabling complications (41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

“…It is a priority to identify accurate risk factors of bone crisis to improve treatment dosage and to avoid this complication. The standard biomarkers related to GD (ChT activity, CCL18/PARC and GluSph concentrations) have been discarded as risk factors for bone complication (50,51) even though their concentration will be increased during bone crisis, due to the acute in ammatory event (45,49). This reminds us of the importance to continue searching for other biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Identification of risk features for complication in Gaucher’s Disease patients: A Machine Learning analysis of the Spanish Registry of Gaucher Disease.

Andrade‐Campos

Frutos

Cebolla

et al. 2020

Preprint

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Background : Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results : A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p=0.005); serum levels of IgA, delayed age at start therapy (>9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (>1750mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions : Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

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Recent Therapeutic Advancements for Gaucher Disease

Pradhan,

Manna,

Pragya

et al. 2024

Advanced Therapeutics

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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.

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Gaucher Disease in Bone: From Pathophysiology to Practice

Cited by 129 publications

References 115 publications

Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

Identification of risk features for complication in Gaucher’s disease patients: a machine learning analysis of the Spanish registry of Gaucher disease

Identification of risk features for complication in Gaucher’s Disease patients: A Machine Learning analysis of the Spanish Registry of Gaucher Disease.

Recent Therapeutic Advancements for Gaucher Disease

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