The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype
Abstract Background The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive dete...
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-019-1232-0 |
| _version_ | 1818459490749513728 |
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| author | Stephanie C. M. Nijmeijer L. Ingeborg van den Born Anneke J. A. Kievit Karolina M. Stepien Janneke Langendonk Jan Pieter Marchal Susanne Roosing Frits A. Wijburg Margreet A. E. M. Wagenmakers |
| author_facet | Stephanie C. M. Nijmeijer L. Ingeborg van den Born Anneke J. A. Kievit Karolina M. Stepien Janneke Langendonk Jan Pieter Marchal Susanne Roosing Frits A. Wijburg Margreet A. E. M. Wagenmakers |
| author_sort | Stephanie C. M. Nijmeijer |
| collection | DOAJ |
| description | Abstract Background The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive deterioration with a rapidly or slowly progressing phenotype. The presented MPS III case series demonstrates adult onset phenotypes with mild cognitive impairment or non-neuronopathic phenotypes. Methods In this case series all adult MPS III patients with a mild- or non-neuronopathic phenotype, who attend the outpatient clinic of 3 expert centers for lysosomal storage disorders were included. A mild- or non-neuronopathic phenotype was defined as having completed regular secondary education and attaining a level of independency during adulthood, involving either independent living or a paid job. Results Twelve patients from six families, with a median age at diagnosis of 43 years (range 3–68) were included (11 MPS IIIA, 1 MPS IIIB). In the four index patients symptoms which led to diagnostic studies (whole exome sequencing and metabolomics) resulting in the diagnosis of MPS III; two patients presented with retinal dystrophy, one with hypertrophic cardiomyopathy and one with neurocognitive decline. The other eight patients were diagnosed by family screening. At a median age of 47 years (range 19–74) 9 out of the 12 patients had normal cognitive functions. Nine patients had retinal dystrophy and 8 patients hypertrophic cardiomyopathy. Conclusion We show the very mild end of the phenotypic spectrum of MPS III, ranging from late-onset stable neurocognitive impairment to a fully non-neuronopathic phenotype. Awareness of this phenotype could lead to timely diagnosis and genetic counseling. |
| first_indexed | 2024-12-14T23:15:11Z |
| format | Article |
| id | doaj.art-ca419429f40643b0b120161dc9fa59a5 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-14T23:15:11Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-ca419429f40643b0b120161dc9fa59a52022-12-21T22:44:06ZengBMCOrphanet Journal of Rare Diseases1750-11722019-11-0114111010.1186/s13023-019-1232-0The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotypeStephanie C. M. Nijmeijer0L. Ingeborg van den Born1Anneke J. A. Kievit2Karolina M. Stepien3Janneke Langendonk4Jan Pieter Marchal5Susanne Roosing6Frits A. Wijburg7Margreet A. E. M. Wagenmakers8Amsterdam UMC, Pediatric Metabolic Diseases, Amsterdam Lysosome Center “Sphinx”, University of AmsterdamThe Rotterdam Eye HospitalErasmus MC, Department of Clinical Genetics, University Medical Center RotterdamSalford Royal NHS Foundation Trust, Adult Inherited Metabolic Disorders, Mark Holland Metabolic UnitErasmus MC, Center for Lysosomal and Metabolic disease, Department of Internal Medicine, University Medical Center RotterdamAmsterdam UMC, Psychosocial Department, Amsterdam Public Health Research Institute, University of AmsterdamRadboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Human GeneticsAmsterdam UMC, Pediatric Metabolic Diseases, Amsterdam Lysosome Center “Sphinx”, University of AmsterdamErasmus MC, Center for Lysosomal and Metabolic disease, Department of Internal Medicine, University Medical Center RotterdamAbstract Background The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive deterioration with a rapidly or slowly progressing phenotype. The presented MPS III case series demonstrates adult onset phenotypes with mild cognitive impairment or non-neuronopathic phenotypes. Methods In this case series all adult MPS III patients with a mild- or non-neuronopathic phenotype, who attend the outpatient clinic of 3 expert centers for lysosomal storage disorders were included. A mild- or non-neuronopathic phenotype was defined as having completed regular secondary education and attaining a level of independency during adulthood, involving either independent living or a paid job. Results Twelve patients from six families, with a median age at diagnosis of 43 years (range 3–68) were included (11 MPS IIIA, 1 MPS IIIB). In the four index patients symptoms which led to diagnostic studies (whole exome sequencing and metabolomics) resulting in the diagnosis of MPS III; two patients presented with retinal dystrophy, one with hypertrophic cardiomyopathy and one with neurocognitive decline. The other eight patients were diagnosed by family screening. At a median age of 47 years (range 19–74) 9 out of the 12 patients had normal cognitive functions. Nine patients had retinal dystrophy and 8 patients hypertrophic cardiomyopathy. Conclusion We show the very mild end of the phenotypic spectrum of MPS III, ranging from late-onset stable neurocognitive impairment to a fully non-neuronopathic phenotype. Awareness of this phenotype could lead to timely diagnosis and genetic counseling.http://link.springer.com/article/10.1186/s13023-019-1232-0Mucopolysaccharidosis type IIISanfilippo syndromePhenotypic spectrumNeuropsychology assessmentLearning difficulties |
| spellingShingle | Stephanie C. M. Nijmeijer L. Ingeborg van den Born Anneke J. A. Kievit Karolina M. Stepien Janneke Langendonk Jan Pieter Marchal Susanne Roosing Frits A. Wijburg Margreet A. E. M. Wagenmakers The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype Orphanet Journal of Rare Diseases Mucopolysaccharidosis type III Sanfilippo syndrome Phenotypic spectrum Neuropsychology assessment Learning difficulties |
| title | The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype |
| title_full | The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype |
| title_fullStr | The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype |
| title_full_unstemmed | The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype |
| title_short | The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype |
| title_sort | attenuated end of the phenotypic spectrum in mps iii from late onset stable cognitive impairment to a non neuronopathic phenotype |
| topic | Mucopolysaccharidosis type III Sanfilippo syndrome Phenotypic spectrum Neuropsychology assessment Learning difficulties |
| url | http://link.springer.com/article/10.1186/s13023-019-1232-0 |
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