Long-term outcome of patients with alpha-mannosidosis – A single center study
Introduction: Alpha-mannosidosis (AM) is a rare autosomal recessive lysosomal storage disease which the natural history has not been exhaustively described yet. The aim of this study was to present the long-term follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecul...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221442692100121X |
| _version_ | 1818331961994772480 |
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| author | Patryk Lipiński Agnieszka Różdżyńska-Świątkowska Katarzyna Iwanicka-Pronicka Barbara Perkowska Paulina Pokora Anna Tylki-Szymańska |
| author_facet | Patryk Lipiński Agnieszka Różdżyńska-Świątkowska Katarzyna Iwanicka-Pronicka Barbara Perkowska Paulina Pokora Anna Tylki-Szymańska |
| author_sort | Patryk Lipiński |
| collection | DOAJ |
| description | Introduction: Alpha-mannosidosis (AM) is a rare autosomal recessive lysosomal storage disease which the natural history has not been exhaustively described yet. The aim of this study was to present the long-term follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecular findings and progression of the disease. Material and methods: The article presents a long-term (over 30 years) observational, retrospective, single-center study of patients with AM. Results: The hearing loss, as one of the first symptoms, was detected in childhood (mean age of 2 years and 6 months) in 10 patients. The other symptoms include: recurrent infections (all patients), inguinal hernias (6 patients), craniosynostosis (1 patient). The mean age at AM diagnosis was 6 years while median was 4 years (age range: 1 year and 8 months – 12 years). The most commonly identified variant in the MAN2B1 gene was c.2245C > T, p.(Arg749Trp). The mean time of follow-up in our study was approximately 14years (range: 1 year – 26 years). Following birth, children with AM grow slowly, finally reaching the 3rd percentile (or values below the 3rd percentile). Hearing loss was not progressive while a gradual exacerbation of intellectual disability with no developmental regression was observed in all patients. Ataxia was diagnosed in 6 patients in the second decade of life (age range 15–20 years). Conclusions: Our study revealed the sensorineural hearing loss as one of the first noted symptom in AM which was congenital and non-progressive during the natural course of disease. A detailed anthropometric phenotype of AM patients was provided with observation of the growth decline during the long-term follow-up. Our study confirmed the existence of two distinguished clinical phenotypes of AM (mild and moderate), and also the lack of clear genotype-phenotype correlation. |
| first_indexed | 2024-12-13T13:28:10Z |
| format | Article |
| id | doaj.art-09b992e8f94b44fba03e6663511a659e |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-13T13:28:10Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-09b992e8f94b44fba03e6663511a659e2022-12-21T23:44:14ZengElsevierMolecular Genetics and Metabolism Reports2214-42692022-03-0130100826Long-term outcome of patients with alpha-mannosidosis – A single center studyPatryk Lipiński0Agnieszka Różdżyńska-Świątkowska1Katarzyna Iwanicka-Pronicka2Barbara Perkowska3Paulina Pokora4Anna Tylki-Szymańska5Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, 04-730 Warsaw, PolandAnthropology Laboratory, The Children's Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Audiology and Phoniatry, The Children's Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, 04-730 Warsaw, Poland; Corresponding author at: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.Introduction: Alpha-mannosidosis (AM) is a rare autosomal recessive lysosomal storage disease which the natural history has not been exhaustively described yet. The aim of this study was to present the long-term follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecular findings and progression of the disease. Material and methods: The article presents a long-term (over 30 years) observational, retrospective, single-center study of patients with AM. Results: The hearing loss, as one of the first symptoms, was detected in childhood (mean age of 2 years and 6 months) in 10 patients. The other symptoms include: recurrent infections (all patients), inguinal hernias (6 patients), craniosynostosis (1 patient). The mean age at AM diagnosis was 6 years while median was 4 years (age range: 1 year and 8 months – 12 years). The most commonly identified variant in the MAN2B1 gene was c.2245C > T, p.(Arg749Trp). The mean time of follow-up in our study was approximately 14years (range: 1 year – 26 years). Following birth, children with AM grow slowly, finally reaching the 3rd percentile (or values below the 3rd percentile). Hearing loss was not progressive while a gradual exacerbation of intellectual disability with no developmental regression was observed in all patients. Ataxia was diagnosed in 6 patients in the second decade of life (age range 15–20 years). Conclusions: Our study revealed the sensorineural hearing loss as one of the first noted symptom in AM which was congenital and non-progressive during the natural course of disease. A detailed anthropometric phenotype of AM patients was provided with observation of the growth decline during the long-term follow-up. Our study confirmed the existence of two distinguished clinical phenotypes of AM (mild and moderate), and also the lack of clear genotype-phenotype correlation.http://www.sciencedirect.com/science/article/pii/S221442692100121Xalpha-MannosidosisLysosomal storage diseaseMAN2B1 geneCongenital sensorineural hearing lossGrowth decline |
| spellingShingle | Patryk Lipiński Agnieszka Różdżyńska-Świątkowska Katarzyna Iwanicka-Pronicka Barbara Perkowska Paulina Pokora Anna Tylki-Szymańska Long-term outcome of patients with alpha-mannosidosis – A single center study Molecular Genetics and Metabolism Reports alpha-Mannosidosis Lysosomal storage disease MAN2B1 gene Congenital sensorineural hearing loss Growth decline |
| title | Long-term outcome of patients with alpha-mannosidosis – A single center study |
| title_full | Long-term outcome of patients with alpha-mannosidosis – A single center study |
| title_fullStr | Long-term outcome of patients with alpha-mannosidosis – A single center study |
| title_full_unstemmed | Long-term outcome of patients with alpha-mannosidosis – A single center study |
| title_short | Long-term outcome of patients with alpha-mannosidosis – A single center study |
| title_sort | long term outcome of patients with alpha mannosidosis a single center study |
| topic | alpha-Mannosidosis Lysosomal storage disease MAN2B1 gene Congenital sensorineural hearing loss Growth decline |
| url | http://www.sciencedirect.com/science/article/pii/S221442692100121X |
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