Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis
Abstract Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasi...
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12144 |
| _version_ | 1818821116938944512 |
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| author | Lucia Santoro Lucia Zampini Lucia Padella Chiara Monachesi Stefania Zampieri Andrea Dardis Rosanna Cordiali Tiziana Galeazzi Carlo Catassi |
| author_facet | Lucia Santoro Lucia Zampini Lucia Padella Chiara Monachesi Stefania Zampieri Andrea Dardis Rosanna Cordiali Tiziana Galeazzi Carlo Catassi |
| author_sort | Lucia Santoro |
| collection | DOAJ |
| description | Abstract Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasible therapeutic option. Only in 2018, the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long‐term treatment of non‐neurological manifestations in mild and moderate forms of alpha‐mannosidosis. In this study, the very early biochemical effects of enzyme replacement therapy in in a 7‐month‐old patient with alpha‐mannosidosis were described. Velmanase alpha was administered as supporting therapy awaiting for hematopoietic stem cell transplantation, the treatment chosen for the patient because of the early onset form. The results showed that the enzyme replacement therapy was able to reduce the content of three different mannosyl‐oligosaccharides monitored by tandem mass spectrometry after 2 months of treatment. In particular, the mean relative changes from baseline values were −67% in urine and −53% in serum at the latest observation. The study also showed that the enzymatic activity detected in serum 1 week after the first infusion was four times higher than the normal values and constant in the following points of observation. These findings led us to assume that velmanase alfa might be biologically active in this young patient. |
| first_indexed | 2024-12-18T23:03:05Z |
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| id | doaj.art-9ebf56554930426e9a909b28441e7465 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-18T23:03:05Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
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| series | JIMD Reports |
| spelling | doaj.art-9ebf56554930426e9a909b28441e74652022-12-21T20:48:31ZengWileyJIMD Reports2192-83122020-09-01551152110.1002/jmd2.12144Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosisLucia Santoro0Lucia Zampini1Lucia Padella2Chiara Monachesi3Stefania Zampieri4Andrea Dardis5Rosanna Cordiali6Tiziana Galeazzi7Carlo Catassi8Department of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyRegional Coordinator Centre for Rare Diseases Academic Hospital "Santa Maria della Misericordia" Udine ItalyRegional Coordinator Centre for Rare Diseases Academic Hospital "Santa Maria della Misericordia" Udine ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyDepartment of Clinical Sciences, Division of Pediatrics Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi Ancona ItalyAbstract Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasible therapeutic option. Only in 2018, the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long‐term treatment of non‐neurological manifestations in mild and moderate forms of alpha‐mannosidosis. In this study, the very early biochemical effects of enzyme replacement therapy in in a 7‐month‐old patient with alpha‐mannosidosis were described. Velmanase alpha was administered as supporting therapy awaiting for hematopoietic stem cell transplantation, the treatment chosen for the patient because of the early onset form. The results showed that the enzyme replacement therapy was able to reduce the content of three different mannosyl‐oligosaccharides monitored by tandem mass spectrometry after 2 months of treatment. In particular, the mean relative changes from baseline values were −67% in urine and −53% in serum at the latest observation. The study also showed that the enzymatic activity detected in serum 1 week after the first infusion was four times higher than the normal values and constant in the following points of observation. These findings led us to assume that velmanase alfa might be biologically active in this young patient.https://doi.org/10.1002/jmd2.12144alpha mannosidosisenzyme replacement therapyHematopoietic cell transplantationliquid chromatography coupled with tandem mass spectrometryoligosaccharidesthin layer chromatography |
| spellingShingle | Lucia Santoro Lucia Zampini Lucia Padella Chiara Monachesi Stefania Zampieri Andrea Dardis Rosanna Cordiali Tiziana Galeazzi Carlo Catassi Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis JIMD Reports alpha mannosidosis enzyme replacement therapy Hematopoietic cell transplantation liquid chromatography coupled with tandem mass spectrometry oligosaccharides thin layer chromatography |
| title | Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis |
| title_full | Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis |
| title_fullStr | Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis |
| title_full_unstemmed | Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis |
| title_short | Early biochemical effects of velmanase alfa in a 7‐month‐old infant with alpha‐mannosidosis |
| title_sort | early biochemical effects of velmanase alfa in a 7 month old infant with alpha mannosidosis |
| topic | alpha mannosidosis enzyme replacement therapy Hematopoietic cell transplantation liquid chromatography coupled with tandem mass spectrometry oligosaccharides thin layer chromatography |
| url | https://doi.org/10.1002/jmd2.12144 |
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