Amsterdam UMC, Pediatric Metabolic Diseases, Amsterdam Lysosome Center "Sphinx", University of Amsterdam, H8-264, Meibergdreef 9, Amsterdam, The Netherlands.
The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
Orphanet J Rare Dis. 2019 Nov 12;14(1):249. doi: 10.1186/s13023-019-1232-0.
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.
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.
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.
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.
许多罕见疾病的表型谱比以前认为的要广泛得多。黏多糖贮积症 III 型（Sanfilippo 综合征，MPS III）是一种溶酶体贮积症，传统上被认为以儿童期发病、进行性神经认知恶化和快速或缓慢进展的表型为特征。本研究中的 MPS III 病例系列展示了成人发病的表型，伴有轻度认知障碍或非神经病变表型。
本病例系列纳入了所有在 3 个溶酶体贮积症专家中心就诊的、具有轻度或非神经病变表型的成年 MPS III 患者。轻度或非神经病变表型定义为完成了正规中等教育，并在成年期获得了独立性，包括独立生活或有薪工作。
纳入了来自 6 个家庭的 12 名患者，中位诊断年龄为 43 岁（范围 3-68 岁）（11 名 MPS IIIA，1 名 MPS IIIB）。在 4 名首发患者中，导致进行诊断研究（全外显子测序和代谢组学）以诊断 MPS III 的症状为：2 名患者表现为视网膜营养不良，1 名患者表现为肥厚型心肌病，1 名患者表现为神经认知下降。其他 8 名患者则通过家系筛查诊断。在中位年龄为 47 岁（范围 19-74 岁）时，12 名患者中有 9 名认知功能正常。9 名患者有视网膜营养不良，8 名患者有肥厚型心肌病。
我们展示了 MPS III 表型谱的非常轻微的一端，从迟发性稳定的神经认知障碍到完全非神经病变表型。对这种表型的认识可能会导致及时诊断和遗传咨询。
