Gaucher's disease type 1: assessment of bone involvement by CT and scintigraphy

Hermann, George; Goldblatt, Jack; Lévy, Roger; Goldsmith, S. J.; Desnick, Robert J.; Grabowski, Gregory A.

doi:10.2214/ajr.147.5.943

Cited by 67 publications

(35 citation statements)

References 5 publications

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“…Computed tomography and magnetic resonance imaging scans of the brain were conducted according to routine procedures. '9mTc-sulfur colloid scans were conducted according to our procedure to avoid artifactual diminution in marrow activity in Gaucher disease due to liver, lung, and splenic uptake (20). Psychomotor evaluations were conducted using the Bayley Scales of Infant Development and the Memll-Palmer Scale of Mental tests in a friendly environment by the same individual who had established rapport with the patient.…”

Section: Methods and Materials The Removed Spleen Mild Respiratory Dmentioning

confidence: 99%

Allogenic Bone Marrow Transplantation in Severe Gaucher Disease

et al. 1992

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ABSTRACT. Gaucher disease is the most prevalent lysoGaucher disease is the most prevalent lysosomal storage disease soma1 storage disease. This autosomal recessive disease is (I) and the most frequent genetic disease in the Ashkenazi Jewish caused by the defective activity of the enzyme acid 8-population (2). This autosomal recessive disorder of glycosphinglucosidase and the resultant accumulation of glucosylcer-golipid metabolism results from numerous point mutations at amide primarily within cells of the reticuloendothelial SyS-the locus-encoding acid (3-glucosidase (glucocerebrosidase) (for tern. Because the primary manifestations of Gaucher review, see Ref. 3). The majority of these are missense mutations, disease are due to involvement of mono~yte/macro~hage-which lead to the defective activity of this enzyme (3-5). The derived this disease is be an resultant accumulation of the substrate, glucosylceramide, within candidate for curative intervention via bone marrow trans-m o n o c y t e~m a c r o p~a g e -~e~v e~ cells (~~~ cells) leads to the ~lantation (BMT). A is panic female with subacute neu-visceral manifestations including hepatosplenomegaly, hyperronopathic Gaucher disease and progressing splenism, and skeletal disease (6). Three variants of the disease manifestations underwent BMT at 23 m0 of age using have been delineated based on the absence (type 1, nonneuronher brother as the donor' Cytoge-opathic) or presence (neuronopathic) and severity (type 2, acute; netic analyses demonstrated complete, stable engraftment by 1 mo post-BMT. During the subsequent 24 mo, clinical, type 3 subacute) of primary CNS involvement (6). Because the biochemical, enzymatic, and histologic studies demon-major visceral manifestations of this disease result from the strated nearly complete correction in the viscera. H~~ accumulation of bone marrow-derived tissue-bound macroneuropathic manifestations did not progress. Complete re-phages, Gaucher disease type 1 has been a prime candidate for constitution of enzymatic activity in peripheral blood leu-curative intervention by BMT. In addition, demonstration of the kocytes was achieved by 1 mo. Cytogenetic analyses dem-clinical, biochemical, and histopathologic efficacy of BMT would onstrated complete engraftment by d 79 and nearly corn-provide the basis for ongoing efforts directed toward molecular plete loss of bone marrow Gaucher cells was observed by therapy for this disease.

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Section: Methods and Materials The Removed Spleen Mild Respiratory Dmentioning

confidence: 99%

Allogenic Bone Marrow Transplantation in Severe Gaucher Disease

et al. 1992

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“…Bone pathology was evaluated by treating clinicians by several methods including X-ray, magnetic resonance imaging (MRI) and bone tomodensitometry. The lesions detected range from diffuse osteoporosis (stage 1), to medullary expansion (stage 2), to osteolysis (stage 3), to necrosis/sclerosis (stage 4), to destruction and collapse (stage 5) (19). One of the earliest clinical signs of bone involvement is the Erlenmeyer flask deformity of the distal femur and the proximal tibia (stage 2) which although not pathognomonic of the disease, is seen in most patients at presentation.…”

Section: Clinical Evaluationmentioning

confidence: 99%

T Cell Numbers Relate to Bone Involvement in Gaucher Disease

Lacerda

Arosa

Lacerda

et al. 1999

Blood Cells, Molecules, and Diseases

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ABSTRACT:The major elements of bone pathology in Gaucher disease are a failure of osteoclast and osteoblast function, resulting in osteopenia and also osteonecrosis. T lymphocytes have recently been found to be involved in the regulation of osteoblast/osteoclast activity in vitro. In the present report the peripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients. A total of 31 patients were studied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized patients present a decrease in absolute numbers of peripheral blood T lymphocytes, specially the CD4 ϩ T subset. However, when patients were analyzed with respect to the presence of bone disease, the number of CD8 ϩ T lymphocytes was found to be statistically significantly lower in patients presenting bone involvement. Furthermore, lower numbers of CD8 ϩ T lymphocytes were significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell activity. These in vivo findings are in agreement with the results reached in vitro by others.

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“…ANOVA showed significant baseline differences among the 3 groups concerning age at diagnosis, splenomegaly, hemoglobin, baseline 99m Tc-sestamibi score, and serum chitotriosidase. Differences were of borderline statistical significance (P 5 0.06) for hepatomegaly, bone pain, and x-ray score (30). No significant differences were observed concerning age at enrollment, sex distribution, platelet count, Zimran SSI, or proportion of patients with prior splenectomy.…”

Section: Patientsmentioning

confidence: 84%

“…Qualitative data are expressed as numbers, followed by percentages in parentheses; continuous data are expressed as mean 6 SD. Zimran SSI and scores for hepatomegaly, splenomegaly, and bone pain are as defined by Zimran et al (28); x-ray score is as defined by Hermann et al (30); and 99m Tc-sestamibi score is as defined by Mariani et al (25).…”

Section: Discussionmentioning

confidence: 99%

^99mTc-Sestamibi Scintigraphy to Monitor the Long-Term Efficacy of Enzyme Replacement Therapy on Bone Marrow Infiltration in Patients with Gaucher Disease

et al. 2013

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Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of 99m Tc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT. Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential 99m Tc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve. We elaborated a dose-response model by statistical analysis based on linear mixed models. Results: Patients whose marrow disease improved had received a significantly higher ERT dose per month than patients who did not improve. Significantly more patients reached near-disappearance of marrow disease if their disease burden at enrollment had been lower and the duration of clinical signs shorter. The response of the marrow scintigraphic score was more pronounced in ERT-naïve patients. No relevant effect of ERT on marrow disease was observed until platelet count and splenomegaly had improved. Conclusion: Although based on localized evaluation, changes in the 99m Tc-sestamibi score closely correlated with the main determinants of ERT, with a definite dose-response relationship. The threshold at which ERT induced any improvement in bone marrow disease was 35-36 U/kg/mo; in ERT-naïve patients, the scintigraphic score declined by 1 unit after ERT at 28 U/kg/mo.

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Gaucher's disease type 1: assessment of bone involvement by CT and scintigraphy

Cited by 67 publications

References 5 publications

Allogenic Bone Marrow Transplantation in Severe Gaucher Disease

Allogenic Bone Marrow Transplantation in Severe Gaucher Disease

T Cell Numbers Relate to Bone Involvement in Gaucher Disease

^99mTc-Sestamibi Scintigraphy to Monitor the Long-Term Efficacy of Enzyme Replacement Therapy on Bone Marrow Infiltration in Patients with Gaucher Disease

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