Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group
Background: Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a chronic progressive neurodegenerative storage disorder caused by a deficiency of lysosomal sulfamidase. The clinical hallmarks are sleep disturbances, behavioral abnormalities and loss of cognitive, speech and motor a...
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| Format: | Article |
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Elsevier
2020-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426920300240 |
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| author | Anja F. Köhn Lorenz Grigull Marcel du Moulin Sarah Kabisch Luise Ammer Cornelia Rudolph Nicole M. Muschol |
| author_facet | Anja F. Köhn Lorenz Grigull Marcel du Moulin Sarah Kabisch Luise Ammer Cornelia Rudolph Nicole M. Muschol |
| author_sort | Anja F. Köhn |
| collection | DOAJ |
| description | Background: Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a chronic progressive neurodegenerative storage disorder caused by a deficiency of lysosomal sulfamidase. The clinical hallmarks are sleep disturbances, behavioral abnormalities and loss of cognitive, speech and motor abilities. Affected children show developmental slowing from the second year of life, dementia occurs by the age of 5 years followed by death in the second decade of life. Only a few studies concerning HSCT in MPS IIIA have been published and do not document a clear benefit of treatment. Methods: The present study summarizes the clinical outcome of a girl with MPS IIIA who received HSCT at the age of 2.5 years. Her clinical course was compared with the natural history of six untreated MPS IIIA patients carrying the same mutations (p.R74C and p. R245H) in the SGSH-gene. Results: Eight years after successful HSCT, the patient showed a global developmental delay. However, cognitive abilities continued to develop, albeit very slowly. There was no sign of regression. She could talk in short sentences, had good motor abilities and performed basic daily living activities by herself. She did not present with sleeping problems, but behavioral abnormalities were profound. In contrast, the six untreated patients with identical mutations in the SGSH-gene showed the typical progressive course of disease with early and continuous loss of abilities. Conclusions: The present data suggest a beneficial effect of HSCT performed at an early stage of MPS IIIA on cognitive skills, motor function and quality of life. |
| first_indexed | 2024-12-23T04:49:19Z |
| format | Article |
| id | doaj.art-05360e7e293545fc98032eca02539e89 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-23T04:49:19Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-05360e7e293545fc98032eca02539e892022-12-21T17:59:31ZengElsevierMolecular Genetics and Metabolism Reports2214-42692020-06-0123Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control groupAnja F. Köhn0Lorenz Grigull1Marcel du Moulin2Sarah Kabisch3Luise Ammer4Cornelia Rudolph5Nicole M. Muschol6Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, GermanyDepartment of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany; Corresponding author at: Department of Pediatrics, International Center for Lysosomal Disorders (ICLD), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.Background: Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a chronic progressive neurodegenerative storage disorder caused by a deficiency of lysosomal sulfamidase. The clinical hallmarks are sleep disturbances, behavioral abnormalities and loss of cognitive, speech and motor abilities. Affected children show developmental slowing from the second year of life, dementia occurs by the age of 5 years followed by death in the second decade of life. Only a few studies concerning HSCT in MPS IIIA have been published and do not document a clear benefit of treatment. Methods: The present study summarizes the clinical outcome of a girl with MPS IIIA who received HSCT at the age of 2.5 years. Her clinical course was compared with the natural history of six untreated MPS IIIA patients carrying the same mutations (p.R74C and p. R245H) in the SGSH-gene. Results: Eight years after successful HSCT, the patient showed a global developmental delay. However, cognitive abilities continued to develop, albeit very slowly. There was no sign of regression. She could talk in short sentences, had good motor abilities and performed basic daily living activities by herself. She did not present with sleeping problems, but behavioral abnormalities were profound. In contrast, the six untreated patients with identical mutations in the SGSH-gene showed the typical progressive course of disease with early and continuous loss of abilities. Conclusions: The present data suggest a beneficial effect of HSCT performed at an early stage of MPS IIIA on cognitive skills, motor function and quality of life.http://www.sciencedirect.com/science/article/pii/S2214426920300240Sanfilippo syndromeMucopolysaccharidosis type IIIMPS IIIAStem cell transplantationHSCTNatural history |
| spellingShingle | Anja F. Köhn Lorenz Grigull Marcel du Moulin Sarah Kabisch Luise Ammer Cornelia Rudolph Nicole M. Muschol Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group Molecular Genetics and Metabolism Reports Sanfilippo syndrome Mucopolysaccharidosis type III MPS IIIA Stem cell transplantation HSCT Natural history |
| title | Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group |
| title_full | Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group |
| title_fullStr | Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group |
| title_full_unstemmed | Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group |
| title_short | Hematopoietic stem cell transplantation in mucopolysaccharidosis type IIIA: A case description and comparison with a genotype-matched control group |
| title_sort | hematopoietic stem cell transplantation in mucopolysaccharidosis type iiia a case description and comparison with a genotype matched control group |
| topic | Sanfilippo syndrome Mucopolysaccharidosis type III MPS IIIA Stem cell transplantation HSCT Natural history |
| url | http://www.sciencedirect.com/science/article/pii/S2214426920300240 |
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