Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening.

BACKGROUND: Pompe disease is a rare, autosomal-recessive disorder which results from a defect in the lysosomal enzyme acid alpha-glucosidase (GAA). The onset of this disease is highly variable, with infantile types being the most severe. Traditionally, lymphocytes, fibroblasts or muscle biopsies were necessary for enzyme activity measurement, because these materials do not express maltase-glucoamylase (MGA) that interferes with the assay. Recently, acarbose was found to inhibit MGA activity selectively, so that dried blood became accessible for GAA assessment. AIM: To evaluate the diagnostic efficacy of GAA measurement in dried blood specimens (DBSs) in comparison with lymphocytes. If DBSs provided reliable results, the diagnosis of Pompe disease could be facilitated, and high-throughput screening would become possible. METHODS AND RESULTS: GAA activity was measured in DBSs of known patients at pH 3.8 (with and without acarbose) and at pH 7.0. Additionally, lymphocytes were obtained from the same patients, and the enzyme activity was determined at pH 4 to pH 7. In total, seven infantile patients and 29 patients with late-onset variants were investigated. All patients were reliably identified by both methods. Furthermore, a simplified protocol was established for neonatal screening. CONCLUSION: The fluorometric technique for the assessment of GAA activity in DBS provides a reliable diagnosis for all variants of Pompe disease. The assay protocol could be simplified for neonatal screening, without increasing the false positive rate significantly or burdening the laboratory with time-consuming procedures.

Eleven-year single-center experience with the ATS Open Pivot Bileaflet heart valve.

BACKGROUND: The ATS Open Pivot Heart Valve was first introduced in 1992 and has been implanted routinely at our institution since 1993. Valve selection was based on surgeon preference. The objective of this study is to retrospectively analyze our 11-year clinical results with ATS prostheses. METHODS: Between January 1993 and December 2003, 601 ATS valves (393 aortic valve replacement [AVR], 168 mitral valve replacement [MVR], 20 aortic plus mitral valve replacement [DVR]) were implanted in 581 patients (377 male, 204 female; mean age, 63.7 years; range 18 to 89). Preoperatively, 47 (8%) were New York Heart Association class I, 212 (36.5%) were class II, 267 (46%) were class III, and 55 (9.5%) were class IV. Preoperative comorbidities were coronary artery disease, 167 (29%); diabetes mellitus, 72 (12%); cerebrovascular disease, 2 (0.3%); endocarditis, 53 (9%); and atrial fibrillation, 115 (20%). RESULTS: Follow-up is 99% complete. Data represent 2,500 cumulative patient-years. Mean follow-up is 4.3 +/- 2.6 years (range, 0.1 to 11.6). Overall hospital mortality is as follows: AVR, 3.8% (15 patients); MVR, 1.8% (3 patients); DVR, 10% (2 patients). Structural valve failure was not encountered. Overall survival at 10 years is AVR, 84.7% +/- 3.1%, AVR plus coronary artery bypass, 67.5% +/- 8.2%; MVR, 59.8% +/- 7.1%, MVR plus coronary artery bypass, 39% +/- 27.8%; and DVR, 74.3% +/- 10%. Freedom from valve-related death at 10 years is AVR, 99.2%; MVR, 94.6%; and DVR, 100%. Linearized rates for postoperative complications are paravalvular leak, 0.6% per patient-year; valve thrombosis, 0.04% per patient-year; thromboembolism, 1.1% per patient-year; major bleeding, 0.5% per patient-year; and de novo prosthesis endocarditis, 0.1% per patient-year. Postoperative mortality risk was significantly elevated by diabetes (p < 0.01), but not by other comorbidities. CONCLUSIONS: Our 11-year experience demonstrates low rates of adverse events and valve-related complications with the ATS Open Pivot heart valve.