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

Stephanie C. M. Nijmeijer¹  Frits A. Wijburg¹  Jan Pieter Marchal²  Janneke Langendonk³  Margreet A. E. M. Wagenmakers³  Anneke J. A. Kievit⁴  Susanne Roosing⁵  Karolina M. Stepien⁶  L. Ingeborg van den Born⁷ 

[1] Amsterdam UMC, Pediatric Metabolic Diseases, Amsterdam Lysosome Center “Sphinx”, University of Amsterdam;Amsterdam UMC, Psychosocial Department, Amsterdam Public Health Research Institute, University of Amsterdam;Erasmus MC, Center for Lysosomal and Metabolic disease, Department of Internal Medicine, University Medical Center Rotterdam;Erasmus MC, Department of Clinical Genetics, University Medical Center Rotterdam;Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Human Genetics;Salford Royal NHS Foundation Trust, Adult Inherited Metabolic Disorders, Mark Holland Metabolic Unit;The Rotterdam Eye Hospital;

关键词: Mucopolysaccharidosis type III;    Sanfilippo syndrome;    Phenotypic spectrum;    Neuropsychology assessment;    Learning difficulties;   

DOI  :  10.1186/s13023-019-1232-0

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown