Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients

El‐Beshlawy, Amal; Ragab, Lamis; Youssry, Ilham; Yakout, Khaled; El-kiki, Hassan Ali; Eid, Khaled; Mansour, Iman; El-Hamid, S. Abd; Yang, Mei; Mistry, Pramod K.

doi:10.1007/s10545-006-0121-6

Cited by 43 publications

(34 citation statements)

References 19 publications

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“…Fractions 2-5 were enriched in lipid rafts, as indicated by the presence of GM1 ( Figure 3A). In untreated RAW264.7 cells ( Figure 3A), M-CSFR was found to reside primarily in the non-raft part of the cell membrane, with only a small proportion associated with the rafts; likewise, TRAF6 was found almost exclusively outside the rafts, while as previously reported (4), a significant proporan iminosugar inhibitor of GCS, is taken up by glucocerebroside-laden macrophages, thus ameliorating the clinical phenotype of Gaucher disease, as well as improving the osteoporotic bone phenotype (21,22).…”

Section: Introductionsupporting

confidence: 81%

Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease

Ersek¹,

Xu²,

Antonopoulos³

et al. 2015

J. Clin. Invest.

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Section: Introductionsupporting

confidence: 81%

Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease

Ersek¹,

Xu²,

Antonopoulos³

et al. 2015

J. Clin. Invest.

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“…Definitive diagnosis of GD requires a simple blood test for acid b-glucosidase enzyme activity in peripheral blood leukocytes as outlined by Charrow et al [24]. Further recommendations for monitoring guidelines and therapeutic goals have been recently established to guide physicians in the management of Gaucher patients [12,25].…”

Section: Discussionmentioning

confidence: 99%

“…We examined the consequences of failure to make a prompt diagnosis and the patient characteristics that correlated with diagnostic delays (Table III). Diagnosis was made by demonstration of low leukocyte acid b-glucosidase activity and sequencing of the acid b-glucosidase gene as previously described [25]. Severity of GD was determined by volumetric measurement of viscera and MRI and radiologic evaluation of bone marrow and skeleton as previously described [26].…”

Section: Case Series Of Diagnostic Delays and Their Consequencesmentioning

confidence: 99%

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

et al. 2007

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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

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“…(17,18) Importantly, it is not known whether osteopenia in GD1 increases the risk of fractures as it does in postmenopausal women. (19) Imiglucerase therapy improves bone mass and bone mineral density (12,13,(20)(21)(22)(23) and studies have shown an apparent decrease in reports of bone pain and bone crises. (23,24) However, it is not known whether imiglucerase treatment decreases the risk of fractures.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Khan

Hangartner

Weinreb³

et al. 2012

Journal of Bone and Mineral Research

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We hypothesized that overall disease activity or the severity of involvement of individual disease compartments, as measured by clinical and surrogate markers, predict the risk of avascular osteonecrosis (AVN) or fractures in type 1 Gaucher disease (GD1). We applied our risk‐set matched case‐control method to identify four patient groups within the International Collaborative Gaucher Group (ICGG) Gaucher Registry based on the presence and absence of AVN and fractures. Characteristics of GD1 were examined by comparing the distributions of each risk factor in cases versus matched controls using conditional logistic regression to calculate adjusted odds ratios (OR). Potential risk factors included hematological and visceral parameters, GD1 biomarkers, white blood cells, GBA1 genotype, and spine and femur dual‐energy X‐ray absorptiometry (DXA) Z‐scores. In the total population of 5894 ICGG Gaucher Registry patients, 544 experienced at least one episode of AVN; 2008 reported no history of AVN. Clinical and surrogate markers of disease activity were similar in patients with and without AVN; patients with AVN were 1.6 times more likely to be anemic compared to matched controls (OR = 1.59; 95% confidence interval [CI], 1.06–2.38, p < 0.05). For fractures, 319 patients suffered fractures and 1233 had no prior history of fractures. Clinical and surrogate markers of disease in patients with and without fractures were similar, except for mean lumbar spine DXA Z‐scores. Among patients with fractures, 49.3% had DXA Z‐scores ≤ −1 compared to 31.0% in the control group. Compared to controls with Z‐scores > −1.0, GD1 patients exhibiting Z‐scores ≤ −1 had an OR of 5.55 (95% CI, 1.81–17.02, p < 0.01) for fracture. In GD1, after controlling for gender, year of birth, treatment status, and splenectomy status, we identified new risk factors for AVN and fractures. Concurrent anemia was associated with an increased risk for AVN. Low bone mineral density of the lumbar spine was a strong risk factor for fractures of the spine and femur in GD1. © 2012 American Society for Bone and Mineral Research.

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Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients

Cited by 43 publications

References 19 publications

Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease

Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease

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

Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

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