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

Objectives: Sialidosis type 1 is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NEU1 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 NEU1 gene. A systematic literature review on sialidosis type 1 was carried out, by the PubMed database was searched using keywords included sialidosis and/or NEU1 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 NEU1 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.