Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease.

BACKGROUND: The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. AIM: To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. METHODS: A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B). RESULTS: A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients' diagnosed ≤1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001). CONCLUSIONS: The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry.

Detection of free hepatitis C virus core antigen by enzyme-linked immunosorbent assay is not suitable for screening of granulocyte colony-stimulating factor-mobilized hematopoietic progenitor donors.

BACKGROUND: Recent studies have shown that hepatitis C virus (HCV) can be detected in peripheral blood mononuclear cells of patients who are negative for the presence of anti-HCV and serum HCV RNA. The aim of the study was to evaluate the prevalence of HCV viremia in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) donors by the use of a free HCV core antigen enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN AND METHODS: A total of 28 samples from consecutive PBPC donors that were mobilized with G-CSF, and 13 samples from patients presenting with leukocytosis of greater than 20 x 10(9) per L from other causes, were tested by a free HCV core antigen ELISA. Positive samples were confirmed by use of neutralization assays. The specificity of the assay was studied in 48,911 healthy blood donors negative for the presence of anti-HCV. RESULTS: The free HCV core antigen assay showed a 46.4 percent positivity in PBPC donors mobilized with G-CSF and 61.5 percent in patients exhibiting leukocytosis in the absence of G-CSF treatment. All the samples were found to be false-positive samples, and those related with growth factor treatment did not react when G-CSF was discontinued. Overall specificity by the test in freshly collected blood donor specimens was 99.62 percent. CONCLUSION: Data indicate that the free HCV core antigen ELISA is not a valid test in diagnosing HCV infection in G-CSF-treated PBPC donors. Moreover, false-positive results of this test on blood donors might be indicative of elevated white blood cell numbers. The low specificity of this assay in the PBPC mobilization setting suggests that molecular assays should be the test of choice in the screening of G-CSF-treated donors.