Multiple Sulfatase Deficiency (MSD) is an inborn error of metabolism caused by pathogenic variants in the SUMF1 gene encoding the formylglycine-generating enzyme (FGE) that activates all known sulfatases. FGE deficiency results in widespread tissue accumulation of multiple sulphated substrates.

Through a systematic analysis of published cases, we retrieved 80 MSD cases and reviewed the disease clinical, biochemical, and genetic findings. Leukodystrophy, neurosensorial hearing loss, and ichthyosis were the most frequent findings at diagnosis. Of 51 reported pathogenic variants, 20 were likely gene disruptive and the remaining were missense variants. No correlations between class of variants and clinical severity or degree of enzyme deficiency were detected. However, cases harboring variants located at N-terminal always had severe neonatal presentations. Moreover, cases with neonatal onset showed the lowest overall survival rate compared to late-infantile and juvenile onsets. Using GnomAD, carrier frequency for pathogenic SUMF1 variants was estimated to be ~1/700 and the disease prevalence was approximately 1/2,000,000.

In summary, MSD is an ultra-rare multisystem disorder with mainly neurologic, hearing and skin involvements. Although the collected data were retrospective and heterogenous, the quantitative data inform the disease natural history and are important for both counseling and design of future interventional studies.

多种硫酸酯酶缺乏症（MSD）是由SUMF1基因的致病变异引起的新陈代谢的先天错误，该基因编码激活所有已知硫酸酯酶的甲酰甘氨酸生成酶（FGE）。FGE缺乏导致多种硫酸化底物的广泛组织积累。

通过对已发表病例的系统分析，我们检索了80例MSD病例，并回顾了该疾病的临床，生化和遗传发现。白细胞营养不良，神经感觉性听力减退和鱼鳞病是诊断时最常见的发现。在报告的51种致病变体中，有20种可能具有基因破坏性，其余为错义变体。没有检测到变体类别与临床严重性或酶缺乏程度之间的相关性。但是，在N末端带有变异的病例总是有严重的新生儿表现。此外，与晚期婴儿和青少年发作相比，新生儿发作的病例显示最低的总生存率。使用GnomAD，病原体SUMF1的载波频率 变异估计为〜1/700，疾病患病率约为1 / 2,000,000。

总之，MSD是一种罕见的多系统疾病，主要涉及神经，听力和皮肤。尽管收集的数据具有回顾性和异质性，但定量数据可告知疾病的自然史，对于咨询和设计未来的干预研究均非常重要。