DOI:10.1259/bjr.75.suppl_1.750001

出版商:British Institute of Radiology    

年代:2002

数据来源: WILEY

摘要:

In Gaucher disease, a genetic deficiency in the activity of the lysosomal enzyme β-glucocerebrosidase (acid β-glucosidase) causes monocytes and macrophages to store excessive amounts of glucocerebroside in lysosomes. The resulting distended cells are called Gaucher cells, and the pathology associated with this condition stems from the accumulation of Gaucher cells in organ systems. The skeletal manifestations are probably the most disabling aspect of the disease. Patients commonly experience bone pain, some suffer bone crises, and up to 20% have impaired mobility. Radiological findings include Erlenmeyer flask deformity, osteopenia, osteosclerosis, osteonecrosis, fractures and bone marrow infiltration. Findings from the Gaucher Registry show that nearly all patients with Gaucher disease have radiological evidence of skeletal involvement, and the majority have a history of serious skeletal complications. Skeletal involvement follows three basic processes: focal disease (irreversible lesions such as osteonecrosis and osteosclerosis), local disease (reversible abnormalities adjacent to heavily involved marrow such as cortical thinning and long bone deformity) and generalized osteopenia. Infarctions are involved in some of the skeletal manifestations, but the mechanisms causing high rates of bone turnover and failure of remodelling are not known. The availability of a β-glucocerebrosidase-deficient mouse model of Gaucher disease with long-term survival should help elucidate the skeletal pathology in Gaucher disease and may ultimately lead to improved management of skeletal complications.

DOI:10.1259/bjr.75.suppl_1.750002

出版商:British Institute of Radiology    

年代:2002

数据来源: WILEY

摘要:

Radiological imaging is used in patients with Gaucher disease to estimate the disease burden, to evaluate the presence of specific skeletal complications and to track response to therapy. MRI is currently the best technique for assessing bone marrow involvement in Gaucher disease. Gaucher cell infiltrated bone marrow is characterized by an abnormal low signal intensity on conventionalT1- andT2-weighted spin echo sequences, owing to a reduction in fat marrow, which gives a high signal intensity. Enzyme replacement therapy results in a degradation of Gaucher cell deposits with a reconversion of marrow fat and consequently an increased signal onT1-weighted images. Conventional MRI also detects other skeletal complications in Gaucher disease, including oedema resulting from acute bone infarction, infection and trauma, avascular necrosis, pathological fractures and vertebral compression. The main drawback of conventional MRI is that it is not quantitative. Quantitative chemical shift imaging is the most sensitive quantitative method for evaluating bone marrow but is not widely available. Alternative MRI-based methods include calculation of theT1relaxation constant and proton spectroscopy. Scoring of imaging changes detected on conventional MRI may be useful in estimating disease burden and risk of complications. Dual-energy X-ray absorptiometry (DXA) is sensitive to generalized osteopenia and changes in bone mineral density with extended enzyme replacement therapy. However, DXA is insensitive to local changes and cannot yet be used to predict fracture risk in these patients. Until the ideal quantitative technique is developed, conventional MRI will remain the best diagnostic modality for assessing skeletal complications in Gaucher disease and monitoring response to enzyme replacement therapy.

DOI:10.1259/bjr.75.suppl_1.750013

出版商:British Institute of Radiology    

年代:2002

数据来源: WILEY

摘要:

In Gaucher disease, enzyme replacement therapy usually reduces liver and spleen volumes and improves haematological abnormalities within 1 year. In contrast, skeletal manifestations of Gaucher disease are thought to respond more slowly. For example, decreased bone marrow glycolipid infiltration and increased bone mineral density have been reported to take up to 3–4 years of treatment. In this report, we present recent studies usingT1- andT2-weighted MRI and quantitative chemical shift imaging that demonstrate decreases in abnormal glucocerebroside infiltration and increases in normal fat content of bone marrow within the first year of treatment. There was no obvious relationship between age, gender, splenectomy status or genotype and the response of bone marrow to therapy. Although the dose of enzyme replacement therapy may be related to bone marrow response, no significant relationship was demonstrated in this report. Long-term enzyme replacement therapy induces continued degradation of Gaucher cell deposits, reconversion of fat marrow and increased bone mineral density. This treatment is also associated with improved or non-progressive bone symptoms and functional status in most adult patients, and it prevents the new occurrence of bone pain and bone crisis in nearly all patients. The development of more sensitive, quantitative imaging methods will help to evaluate disease severity better and to assess the response to therapy.

DOI:10.1259/bjr.75.suppl_1.750025

出版商:British Institute of Radiology    

年代:2002

数据来源: WILEY

摘要:

For paediatric patients with Gaucher disease, enzyme replacement therapy (ERT) has the potential to prevent the development of serious, irreversible skeletal complications. Analysis of skeletal data for paediatric patients receiving ERT must take into account the pubertal growth spurt and developmental changes in bone marrow composition. In a study conducted at the Burlo Garofolo Institute in Trieste, Italy, 10 paediatric patients have received ERT, and data are available for 3–9 years of follow-up. ERT was associated with a significant increase in the mean lumbar bone mineral density (BMD)Zscore after 2 years of treatment (p=0.003). Skeletal growth rates increased among patients exhibiting growth delays. At the Gaucher Disease Treatment Center in Cincinnati, OH, USA, a total of 11 paediatric patients have been followed for 2 years or more of ERT. Of these 11 patients, 6 have demonstrated significant increases in lumbar BMD after 2 years of ERT; these patients tended to have lower BMDZscores at the start of ERT. At the Children's Hospital of the Johannes-Gutenberg University in Mainz, Germany, 7 children with type 1 Gaucher disease presented with reduced BMD in the distal ulna, and after 18–24 months of ERT, these patients demonstrated increases in BMD at this site. The patients exhibiting growth retardation experienced growth acceleration during treatment. These studies suggest that ERT improves BMD and growth rates in paediatric patients with Gaucher disease. ERT in paediatric patients may have the potential to prevent serious skeletal complications such as fractures and vertebral compression later in life.

DOI:10.1259/bjr.75.suppl_1.750037

出版商:British Institute of Radiology    

年代:2002

数据来源: WILEY