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Open Access 01-12-2019 | Cardiomyopathy | Research

The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype

Authors: 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

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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.

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Title: The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype
Authors: 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
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Cardiomyopathy
Published in: Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-019-1232-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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