Multiple Sulfatase Deficiency (MSD, MIM#272200) is an ultra‐rare lysosomal storage disorder arising from mutations in the SUMF1 gene, which encodes the formylglycine‐generating enzyme (FGE). FGE is necessary for the activation of sulfatases, a family of enzymes that are involved in the degradation of sulfated substrates such as glycosaminoglycans and sulfolipids. SUMF1 mutations lead to functionally impaired FGE and individuals with MSD demonstrate clinical signs of single sulfatase deficiencies, including metachromatic leukodystrophy (MLD) and several mucopolysaccharidosis (MPS) subtypes. Comprehensive information related to the natural history of MSD is missing. We completed a systematic literature review and a meta‐analysis on data from published cases reporting on MSD. As available from these reports, we extracted clinical, genetic, biochemical, and brain imaging information. We identified 75 publications with data on 143 MSD patients with a total of 53 unique SUMF1 mutations. The mean survival was 13 years (95% CI 9.8‐16.2 years). Seventy‐five clinical signs and 11 key clusters of signs were identified. The most frequently affected organs systems were the nervous, skeletal, and integumentary systems. The most frequent MRI features were abnormal myelination and cerebral atrophy. Individuals with later onset MSD signs and survived longer than those with signs at birth. Less severe mutations, low disease burden and achievement of independent walking positively correlated with longer survival. Despite the limitations of our approach, we were able to define clinical characteristics and disease outcomes in MSD. This work will provide the foundation of natural disease history data needed for future clinical trial design.

中文翻译：

---

对已发表病例的系统评价和荟萃分析揭示了多种硫酸酯酶缺乏症的自然病史。

多硫酸酯酶缺乏症 (MSD, MIM#272200) 是一种极罕见的溶酶体贮积症，由编码甲酰甘氨酸生成酶 (FGE)的SUMF1基因突变引起。FGE 是激活硫酸酯酶所必需的，硫酸酯酶是参与硫酸化底物（如糖胺聚糖和硫脂）降解的酶家族。SUMF1突变导致 FGE 功能受损，MSD 患者表现出单一硫酸酯酶缺陷的临床症状，包括异染性脑白质营养不良 (MLD) 和几种粘多糖贮积症 (MPS) 亚型。缺少与 MSD 自然病程相关的综合信息。我们完成了对已发表的 MSD 病例报告数据的系统文献回顾和荟萃分析。根据这些报告，我们提取了临床、遗传、生化和脑成像信息。我们确定了 75 篇出版物，其中包含 143 名 MSD 患者的数据，共有 53 个独特的SUMF1突变。平均生存期为 13 年（95% CI 9.8-16.2 年）。确定了 75 个临床体征和 11 个关键体征群。最常受影响的器官系统是神经、骨骼和外皮系统。最常见的 MRI 特征是髓鞘形成异常和脑萎缩。较晚出现 MSD 体征的个体比出生时出现体征的个体存活时间更长。不太严重的突变、低疾病负担和独立行走的成就与更长的生存期呈正相关。尽管我们的方法存在局限性，但我们能够定义 MSD 的临床特征和疾病结果。这项工作将为未来临床试验设计所需的自然病史数据提供基础。