一个土耳其家庭中的1型唾液酸贮积症：病例报告及文献复习

Sialidosis type 1 in a Turkish family: a case report and review of literatures.

作者信息

Kılıç Mustafa, İcil Suzan, Sezer Abdullah, Kaya-Güneş Öznur, Comoğlu Selim S

机构信息

Department of Pediatrics, Metabolism Unit, Ankara Etlik City Hospital, Ankara, Türkiye.

Department of Genetics, Ankara Etlik City Hospital, Ankara, Türkiye.

出版信息

J Pediatr Endocrinol Metab. 2024 Dec 30;38(2):176-186. doi: 10.1515/jpem-2024-0468. Print 2025 Feb 25.

DOI:10.1515/jpem-2024-0468

PMID:39733340

Abstract

OBJECTIVES

Sialidosis type 1 is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the gene, which encodes the sialic acid-degrading enzyme α-neuraminidase. Sialidosis type 1 is a milder form with a late-onset phenotype, characterized by progressive myoclonic epilepsy and ataxia with cherry-red spots. Sialidosis type 2 is an early-onset and more severe form presenting with dysmorphic features, hepatosplenomegaly and cognitive delay. Clinical diagnosis is usually supported by increased urinary bound sialic acid excretion and confirmed by genetic analysis or demonstration of α-neuraminidase enzyme deficiency in cultured fibroblasts. The aim of this study was to present a case of type 1 sialidosis, review the literature, and investigate genotype-phenotype correlations, symptom frequencies, and race-specific mutations in patients diagnosed with type 1 sialidosis.

CASE PRESENTATION

We report herein a family of four Turkish siblings affected with sialidosis type 1 associated with a homozygous variant, c.403G>A p. (Asp135Asn), in the gene. A systematic literature review on sialidosis type 1 was carried out, by the PubMed database was searched using keywords included sialidosis and/or gene. We selected case reports or series that included genetically confirmed type 1 sialidosis from 1996 to 2023. So far, nearly genetically confirmed 80 patients from unrelated 65 families, more than 40 disease causing mutations, have been identified in patients with sialidosis type 1. Among the reported mutations, missense variants are the most common, and few nonsense, frameshift, exonic duplications or small deletions have been reported. c.239C>T p. (Pro80Leu) variant in Chinese and Japanese patients, c.649G>A p. (Val217Met) variant in Japanese patients, c.880C>T p. (Arg294Cys) variant in Indian patients, c.629C>T p. (Pro210Leu) variant in Ecuadorian patients, c.982G>A p. (Gly328Ser) variant in Italian patients, and c.403G>A p (Asp135Asn) and c.625del p. (Glu209Serfs*94) variants in Turkish patients were found higher.

CONCLUSIONS

Race-specific variants were found with higher percentages in certain populations.

摘要

目的

1型唾液酸沉积症是一种罕见的常染色体隐性溶酶体贮积症，由编码唾液酸降解酶α-神经氨酸酶的基因中的致病变异引起。1型唾液酸沉积症是一种较轻的类型，具有晚发型表型，其特征为进行性肌阵挛癫痫和伴有樱桃红斑的共济失调。2型唾液酸沉积症是早发型且更严重的类型，表现为畸形特征、肝脾肿大和认知延迟。临床诊断通常通过尿结合唾液酸排泄增加来支持，并通过基因分析或培养成纤维细胞中α-神经氨酸酶缺乏的证明来确诊。本研究的目的是报告一例1型唾液酸沉积症病例，回顾文献，并研究确诊为1型唾液酸沉积症患者的基因型-表型相关性、症状频率和种族特异性突变。

病例报告

我们在此报告一个土耳其家庭的四名兄弟姐妹患1型唾液酸沉积症，与该基因中的纯合变异c.403G>A p.（Asp135Asn）相关。对1型唾液酸沉积症进行了系统的文献综述，通过PubMed数据库使用包括唾液酸沉积症和/或该基因的关键词进行检索。我们选择了1996年至2023年期间包括基因确诊的1型唾液酸沉积症的病例报告或系列研究。到目前为止，在1型唾液酸沉积症患者中已鉴定出近80例来自65个无关家庭的基因确诊患者、40多种致病突变。在报告的突变中，错义变异最为常见，很少有报道无义、移码、外显子重复或小缺失。在中国和日本患者中发现c.239C>T p.（Pro80Leu）变异，在日本患者中发现c.649G>A p.（Val217Met）变异，在印度患者中发现c.880C>T p.（Arg294Cys）变异，在厄瓜多尔患者中发现c.629C>T p.（Pro210Leu）变异，在意大利患者中发现c.982G>A p.（Gly328Ser）变异，在土耳其患者中发现c.403G>A p（Asp135Asn）和c.625del p.（Glu209Serfs*94）变异的比例较高。