Symptomatic patients with Gaucher disease (GD) (acid -glucosidase [Gcase] deficiency) are treated with injectable human recombinant GCase. Treatment results in significant decreases in lipid storage in liver, spleen, and bone marrow, but the generalized osteopenia and focal bone lesions present in many adult patients are refractory to treatment. A double-blind, 2-arm, placebo-controlled trial of alendronate (40 mg/d) was performed in adults with GD who had been treated with enzyme for at least 24 months. Primary therapeutic endpoints were improvements in (1) bone mineral density (BMD) and content (BMC) at the lumbar spine, and (2) focal lesions in x-rays of long bones assessed by a blinded reviewer. There were 34 patients with GD type 1 (age range, 18-50 years) receiving enzyme therapy who were randomized for this study. After 18 months, ⌬BMD at the lumbar spine was 0.068 ؎ 0.21 and 0.015 ؎ 0.034 for alendronate and placebo groups, respectively (P ؍ .001). Long-bone x-rays showed no change in focal lesions or bone deformities in any subject in either arm. Alendronate is a useful adjunctive therapy in combination with enzyme replacement therapy (ERT) for the treatment of GD-related osteopenia in adults, but it cannot be expected to improve focal
The radiology department at a midwestern U.S. children's hospital has created a scorecard that is presented quarterly to the institutional leadership and is available to all radiology employees on the institutional intranet. The scorecard currently has 33 measures in six areas: clinical services (safety, quality, timeliness); education; research; professionalism, communication, and user satisfaction; finances and administration; and staffing. For each measure, the goal, current value of the measure, interval at which the measure is updated, date of last update, and previous value of the measure are listed. Each measure was reviewed over time to determine those measures for which target goals were met. Results indicate that a visible and transparent department scorecard is one of the more powerful tools available to the radiology leadership to call attention to and improve performance in specific areas. The use of such a scorecard can help develop a departmental culture of quality improvement, focus healthcare providers on specific quality improvement projects, and drive departmental performance.
Gaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid β-glucosidase locus. Periodic infusions of macrophage-targeted acid β-glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid β-glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid β-glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid β-glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid β-glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.
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