Skeletal Complications of Gaucher Disease

Stowens, Daniel; Teitelbaum, Steven L.; Kahn, Arnold J.; Barranger, John A.

doi:10.1097/00005792-198509000-00003

Cited by 164 publications

(91 citation statements)

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“…Further, the myocardial involvement observed in GD (Platzker et al 1985;Torloni et al 2002) has been explained solely by the infiltration of the heart by GCs (Edwards et al 1983;Smith et al 1978), while the syndrome of pulmonary hypertension is thought to be caused by GCs occupying the lumina of the alveolar capillaries or alveoli (Mistry et al 2002), although this syndrome has been described in the absence pulmonary GCs (Theise and Ursell 1990). Lastly, bone involvement leading to 'bone crises' (Beighton et al 1982) is also awaiting an explanation that goes beyond the mere presence of GCs (Fiore et al 2002;Stowens et al 1985;Wenstrup et al 2002). The enhanced expression of cysteine proteinases in GCs and other cells might contribute to lytic bone lesions (Moran et al 2000).…”

Section: Glucosylceramide Transfermentioning

confidence: 99%

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Elleder

2006

J of Inher Metab Disea

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SummaryGaucher disease (GD), deficiency of acid glucosylceramidase (GlcCer‐ase) is characterized by deficient degradation of beta‐glucosylceramide (GlcCer). It is well known that, in GD, the lysosomal accumulation of uncleaved GlcCer is limited to macrophages, which are gradually converted to storage cells with well known cytology—Gaucher cells (GCs). On the basis of previous studies of the disorder and of a comparison with other lysosomal enzymopathies affecting degradation of the GlcCer‐based glycosphingolipid series, it is hypothesized that in other cell types (i.e. non‐macrophage cells) the uncleaved GlcCer, in GlcCer‐ase deficiency, is transferred to other cell compartments, where it may be processed and even accumulated to various degrees. The consequence of the abnormal extralysosomal load may differ according to the cell type and compartment targeted and may be influenced by genetically determined factors, by a number of acquired conditions, including the current metabolic situation. The sequelae of the uncleaved GlcCer extralysosomal transfer may range from probably innocent or positive stimulatory, to the much more serious, in which it interferes with a variety of cell functions, and in extreme cases, can lead to cell death. This alternative processing of uncleaved GlcCer may help to explain tissue alterations seen in GD that have, so far, resisted explanation based simply on the presence of GCs. Paralysosomal alternative processing may thus go a long way towards filling a long‐standing gap in the understanding of the molecular pathology of the disorder. The impact of this alternative process will most likely be inversely proportional to the level of residual GlcCer‐ase activity. Lysosomal sequestration of GlcCer in these cells is either absent or in those exceptional cases where it does occur, it is exceptional and rudimentary. It is suggested that paralysosomal alternative processing of uncleaved GlcCer is the main target for enzyme replacement therapy. The mechanism responsible for GlcCer transfer remains to be elucidated. It may also help in explaining the so far unclear origin of glucosylsphingosine (GlcSph) and define the mutual relation between these two processes.

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Section: Glucosylceramide Transfermentioning

confidence: 99%

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Elleder

2006

J of Inher Metab Disea

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“…Skeletal symptoms may occur at any time in life. Skeletal manifestations are major determinants of morbidity, 5,9,10 and encompass generalised osteopenia with osteoporosis, focal deformities (e.g. Erlenmeyer flask deformity of the distal femur), bone lesions of various types including lytic lesions, osteosclerosis, and pathological fractures, occurring at various sites, especially the femoral head and neck but also humeri, vertebral bodies, tibiae, ribs, pelvis and others.…”

Section: Bone Diseasementioning

confidence: 99%

“…Five of these concerned skeletal complications, four considered the relationship between skeletal and visceral symptoms, including the impact of splenectomy, and the remainder considered skeletal symptoms in isolation, pulmonary symptoms, growth retardation or pregnancy in Gaucher's disease. 10,74,77,[136][137][138][139][140][141][142][143][144][145][146][147] The review concentrates on the papers that report multiple clinical characteristics. The other papers are used to inform our understanding of the relationship between the different clinical characteristics; such as splenectomy and bone disease.…”

Section: Quantity and Quality Of Research Availablementioning

confidence: 99%

“…With a gradual abatement of all symptoms, the episode usually resolves within 2 to 4 weeks". 10 Femora, vertebrae and humeri are the most frequently affected bones in Gaucher's disease; however, bone changes have been reported in "ribs, radii, ulnae, mandibles, carpal, metacarpal, pelvic and phalangeal bones". 10 In addition to acute bone pain, people with type I Gaucher's disease report arthritis-like pain, osteopenia and osteoporosis.…”

Section: Natural History: Skeletal Symptoms Of Gaucher's Diseasementioning

confidence: 99%

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The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gauchers disease: a systematic review

2007

Clinical Governance: An International Journal

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“…17 Skeletal disease affects more than 80 % of patients with Gaucher disease and can have a major impact on patient quality of life. 18,19 • Impaired neutrophil function and neutropenia may cause an increased susceptibility to infection.…”

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confidence: 99%

A Rare Condition in Haematological Practice – Gaucher Disease

Cappellini

2015

European Oncology &Amp; Haematology

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Gaucher disease, which is caused by an inherited glucocerebrosidase deficiency, is the most prevalent lysosomal storage disease worldwide. Estimated prevalence of Gaucher disease is 1:50,000 in most countries and the disease has its highest incidence in the Ashkenazi Jewish population. Type 1 (non-neuropathic) Gaucher disease is by far the most common form. Gaucher disease type 1 should be considered in cases of unexplained splenomegaly with or without bleeding diathesis, skeletal manifestations or hepatomegaly. Diagnosis is made by demonstrating decreased glucocerebrosidase activity in peripheral blood leucocytes. Dried blood spots can be used for screening but conventional enzyme assay on heparinised blood is essential. Patients with Gaucher disease may have extensive organ involvement despite relatively minor overt symptomatology. Evidence suggests that Gaucher disease may remain undiagnosed for years, leading to severe complications that are preventable or reversible with enzyme replacement therapy. These complications include avascular necrosis, severe bleeding, chronic bone pain, pathological fractures, growth failure, liver pathology and life-threatening sepsis. Most patients with Gaucher disease are initially evaluated by a haematologist–oncologist. Improved education is needed to enable prompt detection of Gaucher disease. An increased risk of multiple myeloma and haematological and non-haematological malignancies has been reported in type 1 Gaucher disease. This review aims to offer familiarisation with a rare disorder in haematological practice, focusing on adult patient management.

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Skeletal Complications of Gaucher Disease

Cited by 164 publications

References 0 publications

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gauchers disease: a systematic review

A Rare Condition in Haematological Practice – Gaucher Disease

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Skeletal Complications of Gaucher Disease

Cited by 164 publications

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Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gauchers disease: a systematic review

A Rare Condition in Haematological Practice – Gaucher Disease

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The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gauchers disease: a systematic review