From the Departments of Neuropathology (R.S., Y.T.C.) and Neurology (R.R.M., P.K.K.), National Institute of Mental Health and Neurosciences, Bengaluru, India.
Neurology. 2023 Oct 10;101(15):e1572-e1576. doi: 10.1212/WNL.0000000000207647. Epub 2023 Jul 24.
Mucopolysaccharidosis IIID (MPS IIID/Sanfilippo syndrome D, OMIM # 252940) is an autosomal recessive lysosomal storage disorder (LSD) and the rarest form of the mucopolysaccharidosis (MPS) III subtypes. It is caused by sequence variations in the gene encoding lysosomal enzyme N-acetyl glucosamine-6-sulphatase (GNS). Deficiency of GNS impairs catabolism of glycosaminoglycans causing accumulation of heparan sulphate within lysosomes of various tissues, which is visualized as membranous cytoplasmic bodies (MCBs) on electron microscopy. The recognition of this ultrastructural feature in a muscle biopsy instigated genetic evaluation for LSD in our case resulting in the detection of a novel pathogenic gene variant. The patient also exhibited intellectual disability since childhood, reduced vision due to pigmentary retinopathy, and behavioral abnormalities without other systemic features of MPS. In this study, we report a patient of Indian origin with MPS IIID based on a novel pathogenic variant c.1078 G>T (p.G360C) in the and the presence of MCBs in muscle biopsy, characterized by several novel findings including the occurrence of pigmentary retinopathy, which extends the clinical spectrum of MPS IIID.
黏多糖贮积症 IIID（MPS IIID/桑菲利斯综合征 D，OMIM#252940）是一种常染色体隐性溶酶体贮积症（LSD），也是黏多糖贮积症（MPS）III 型中最罕见的类型。它是由编码溶酶体酶 N-乙酰氨基葡萄糖-6-硫酸酯酶（GNS）的基因序列变异引起的。GNS 的缺乏会损害糖胺聚糖的分解代谢，导致各种组织的溶酶体中硫酸乙酰肝素的积累，这在电子显微镜下表现为膜细胞质体（MCB）。在肌肉活检中发现这种超微结构特征后，我们对 LSD 进行了遗传评估，从而发现了一种新的致病性基因突变。该患者自童年起就存在智力障碍、色素性视网膜炎导致的视力下降以及行为异常，但没有 MPS 的其他全身特征。在本研究中，我们报告了一名来自印度的 MPS IIID 患者，该患者在基因中存在 c.1078G>T（p.G360C）的新型致病性变异，并且在肌肉活检中存在 MCB，其特征是存在几种新的发现，包括色素性视网膜炎的发生，这扩展了 MPS IIID 的临床谱。
