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Heparan sulfate and dermatan sulfate disaccharide levels for newborn screening in MPS I, MPS II and MPS III
Abstracts
hospital infusions without premedication and shows improvement of clinical and laboratory parameters. Conclusion: This is the first report of the use of alfavelaglucerase in patients with GD type 3. Premedication and slower infusion rate reduce the incidence of adverse events but may not solve the problem of severe reactions. This case report further demonstrates the different safety profile among all the recombinant enzymes available for the treatment of GD.
doi:10.1016/j.ymgme.2012.11.258
245 Heparan sulfate and dermatan sulfate disaccharide levels for newborn screening in MPS I, MPS II and MPS III Naomi van Vliesa, Jessica de Ruijterb, Minke de Rub, Tom Wagemansa, Lodewijk IJlstc, Frits Wijburgb, aDepartment of Pediatrics and Amsterdam Lysosome Centre ‘Sphinx’, Lab. Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, Noord holland, The Netherlands, bDepartment of Pediatrics and Amsterdam Lysosome Centre ‘Sphinx’, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, cLab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders characterized by accumulation of glycosaminoglycans and severe and progressive disease. To date, disease modifying therapy is available for three of the MPS and is being developed for the other types. Early initiation of treatment, before the onset of irreversible tissue damage, provides a favorable disease outcome. Early diagnosis, however, is difficult due to the rarity and the wide variety of clinical symptoms of these disorders. Newborn screening (NBS) would probably be the optimal approach for early diagnosis and several screening techniques for different MPS have been studied. We collected newborn dried blood spots (DBS) of controls, heterozygotes and 11 MPS I and 6 MPS III patients, with phenotypes ranging from severe to relatively attenuated, and one MPS II patient and determined the levels of dermatan and heparan sulfate derived disaccharides with HPLC–MS/MS. Our method reliably separates the MPS newborns from controls and heterozygotes, as dermatan and heparan sulfate levels were clearly elevated in all newborn DBS of MPS patients when compared to controls and heterozygotes. Our study demonstrates that measurement of heparan and dermatan sulfate derived disaccharides in DBS may be suitable for NBS for MPS I, MPS II and MPS III. We hypothesize that this same approach will also detect MPS VI, and VII patients, as heparan sulfate and/or dermatan sulfate are also the primary storage products in these disorders.
doi:10.1016/j.ymgme.2012.11.259
S95
present the follow up of 11 patients (9 type 1, 2 type 3) a year after beginning enzyme replacement therapy. Methods: Clinical findings, genetic analyses, laboratory work up, liver and spleen volumes were analyzed. Results: Mean age was 15.9 years (11–24 years); mean age at diagnosis was 8.2 years (5–14 years). Most common presenting symptom was hepatosplenomegaly (all patients). Most common mutation was heterozygous N370S. One patient had severe anemia and four moderate anemia before the treatment. Ten patients had thrombocytopenia. All patients had high levels of chitotriosidase before the treatment (266 times higher than normal value). A year after the treatment we found a patient with moderate anemia, a patient with thrombocytopenia, eight patients with slight hepatosplenomegaly, and the level of chitotriosidase was reduced significantly in all patients (13 times higher than normal value). Conclusion: We conclude that level of chitotriosidase was more sensitive method to follow up of pediatric Gaucher patients during the first year of treatment. doi:10.1016/j.ymgme.2012.11.260
247 Carotid intima–media thickness is increased in patients with mucopolysaccharidoses Types I, II, and VI and is correlated with arterial stiffness Raymond Wanga, Elizabeth Braunlinb, Kelly Covaulta, Andrea Metzigb, Kyle Rudserc, Donald Dengeld, Lynda Polgreenb, Elsa Shapirob, Julia Steinbergerb, Aaron Kellyb, aCHOC Children's, Orange, CA, USA, b Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA, cDivision of Biostatistics, University of Minnesota, School of Public Health, Minneapolis, MN, USA, dSchool of Kinesiology, University of Minnesota, Minneapolis, MN, USA Background: Treatments for mucopolysaccharidoses (MPS) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima–media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: To determine if cIMT and arterial stiffness are abnormal in treated MPS I, II, and VI patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography and electronic wall-tracking software (Medical Imaging Applications, Coralville, IA) was used to measure cIMT, compliance (cCSC), distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results are reported as mean± SD. Results: 16 MPS patients were studied (10 MPS I, 4 MPS II, 2 MPS VI). MPS patients had higher cIMT (0.56 ± 0.04 mm) compared to controls (0.44 ± 0.04 mm; p b 0.001). In MPS patients only, cCSD (−14.34%/ 0.05 mm, p = 0.022) and cIEM were correlated with cIMT (549 mm Hg/ 0.05 mm, p = 0.008). Study data is summarized in Fig. 1.
246 Follow up of Gaucher patients in “Mother Teresa Hospital” Tirana — Albania Virtut Velmishi, Ermira Dervishi, Paskal Cullufi, Mother Teresa Hospial, Tirana, Albania Aim: Gaucher disease is a multisystemic disorder characterized by glucocerebrosidase enzyme deficiency. The aim of this study was to
Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The
hospital infusions without premedication and shows improvement of clinical and laboratory parameters. Conclusion: This is the first report of the use of alfavelaglucerase in patients with GD type 3. Premedication and slower infusion rate reduce the incidence of adverse events but may not solve the problem of severe reactions. This case report further demonstrates the different safety profile among all the recombinant enzymes available for the treatment of GD.
doi:10.1016/j.ymgme.2012.11.258
245 Heparan sulfate and dermatan sulfate disaccharide levels for newborn screening in MPS I, MPS II and MPS III Naomi van Vliesa, Jessica de Ruijterb, Minke de Rub, Tom Wagemansa, Lodewijk IJlstc, Frits Wijburgb, aDepartment of Pediatrics and Amsterdam Lysosome Centre ‘Sphinx’, Lab. Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, Noord holland, The Netherlands, bDepartment of Pediatrics and Amsterdam Lysosome Centre ‘Sphinx’, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, cLab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders characterized by accumulation of glycosaminoglycans and severe and progressive disease. To date, disease modifying therapy is available for three of the MPS and is being developed for the other types. Early initiation of treatment, before the onset of irreversible tissue damage, provides a favorable disease outcome. Early diagnosis, however, is difficult due to the rarity and the wide variety of clinical symptoms of these disorders. Newborn screening (NBS) would probably be the optimal approach for early diagnosis and several screening techniques for different MPS have been studied. We collected newborn dried blood spots (DBS) of controls, heterozygotes and 11 MPS I and 6 MPS III patients, with phenotypes ranging from severe to relatively attenuated, and one MPS II patient and determined the levels of dermatan and heparan sulfate derived disaccharides with HPLC–MS/MS. Our method reliably separates the MPS newborns from controls and heterozygotes, as dermatan and heparan sulfate levels were clearly elevated in all newborn DBS of MPS patients when compared to controls and heterozygotes. Our study demonstrates that measurement of heparan and dermatan sulfate derived disaccharides in DBS may be suitable for NBS for MPS I, MPS II and MPS III. We hypothesize that this same approach will also detect MPS VI, and VII patients, as heparan sulfate and/or dermatan sulfate are also the primary storage products in these disorders.
doi:10.1016/j.ymgme.2012.11.259
S95
present the follow up of 11 patients (9 type 1, 2 type 3) a year after beginning enzyme replacement therapy. Methods: Clinical findings, genetic analyses, laboratory work up, liver and spleen volumes were analyzed. Results: Mean age was 15.9 years (11–24 years); mean age at diagnosis was 8.2 years (5–14 years). Most common presenting symptom was hepatosplenomegaly (all patients). Most common mutation was heterozygous N370S. One patient had severe anemia and four moderate anemia before the treatment. Ten patients had thrombocytopenia. All patients had high levels of chitotriosidase before the treatment (266 times higher than normal value). A year after the treatment we found a patient with moderate anemia, a patient with thrombocytopenia, eight patients with slight hepatosplenomegaly, and the level of chitotriosidase was reduced significantly in all patients (13 times higher than normal value). Conclusion: We conclude that level of chitotriosidase was more sensitive method to follow up of pediatric Gaucher patients during the first year of treatment. doi:10.1016/j.ymgme.2012.11.260
247 Carotid intima–media thickness is increased in patients with mucopolysaccharidoses Types I, II, and VI and is correlated with arterial stiffness Raymond Wanga, Elizabeth Braunlinb, Kelly Covaulta, Andrea Metzigb, Kyle Rudserc, Donald Dengeld, Lynda Polgreenb, Elsa Shapirob, Julia Steinbergerb, Aaron Kellyb, aCHOC Children's, Orange, CA, USA, b Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA, cDivision of Biostatistics, University of Minnesota, School of Public Health, Minneapolis, MN, USA, dSchool of Kinesiology, University of Minnesota, Minneapolis, MN, USA Background: Treatments for mucopolysaccharidoses (MPS) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima–media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives: To determine if cIMT and arterial stiffness are abnormal in treated MPS I, II, and VI patients compared to healthy controls. Methods: MPS patients underwent carotid artery ultrasonography and electronic wall-tracking software (Medical Imaging Applications, Coralville, IA) was used to measure cIMT, compliance (cCSC), distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results are reported as mean± SD. Results: 16 MPS patients were studied (10 MPS I, 4 MPS II, 2 MPS VI). MPS patients had higher cIMT (0.56 ± 0.04 mm) compared to controls (0.44 ± 0.04 mm; p b 0.001). In MPS patients only, cCSD (−14.34%/ 0.05 mm, p = 0.022) and cIEM were correlated with cIMT (549 mm Hg/ 0.05 mm, p = 0.008). Study data is summarized in Fig. 1.
246 Follow up of Gaucher patients in “Mother Teresa Hospital” Tirana — Albania Virtut Velmishi, Ermira Dervishi, Paskal Cullufi, Mother Teresa Hospial, Tirana, Albania Aim: Gaucher disease is a multisystemic disorder characterized by glucocerebrosidase enzyme deficiency. The aim of this study was to
Conclusions: Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The