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12 pages, 1345 KB

Open AccessReview

Genetic Insights and Clinical Implications of NEU1 Mutations in Sialidosis

by Mei-Ling Peng, Siu-Fung Chau, Jia-Ying Chien, Peng-Yeong Woon, Yu-Chen Chen, Wai-Man Cheang, Hsien-Yang Tsai and Shun-Ping Huang

Genes 2025, 16(2), 151; https://doi.org/10.3390/genes16020151 - 25 Jan 2025

Cited by 11 | Viewed by 3431

Abstract

Sialidosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the NEU1 gene, resulting in deficient neuraminidase-1 activity and the subsequent accumulation of sialylated compounds in lysosomes. This review comprehensively analyzes the genetic and clinical heterogeneity associated with sialidosis, emphasizing the distinction between the milder type I form and the more severe type II form. Over 90 pathogenic NEU1 variants, predominantly missense mutations, have been identified, highlighting significant phenotypic diversity. Advancements in genomic sequencing technologies have facilitated the identification of known and novel mutations, with population-specific insights elucidating ethnic variability in symptomatology and genetic profiles. Recent case studies, including a novel compound heterozygous variant, further illustrate the complexity of the genotype–phenotype correlations. Emerging therapeutic approaches, such as enzyme replacement therapy and adeno-associated virus-mediated gene therapy, demonstrate promising potential for restoring neuraminidase-1 function and improving outcomes in preclinical models. This review emphasizes the critical role of genetic analysis in diagnosis and management while advocating for continued research into the molecular mechanisms underlying sialidosis to enable the development of targeted, personalized treatments. Full article

(This article belongs to the Special Issue Genes and Variants in Human Rare Genetic Diseases)

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14 pages, 300 KB

Open AccessReview

The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases

by Brianna M. Naumchik, Ashish Gupta, Heather Flanagan-Steet, Richard A. Steet, Sara S. Cathey, Paul J. Orchard and Troy C. Lund

Cells 2020, 9(6), 1411; https://doi.org/10.3390/cells9061411 - 5 Jun 2020

Cited by 23 | Viewed by 5659

Abstract

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders. Full article

(This article belongs to the Special Issue Lysosomal Storage Disorders)

16 pages, 1140 KB

Open AccessReview

Sialidosis: A Review of Morphology and Molecular Biology of a Rare Pediatric Disorder

by Aiza Khan and Consolato Sergi

Diagnostics 2018, 8(2), 29; https://doi.org/10.3390/diagnostics8020029 - 25 Apr 2018

Cited by 60 | Viewed by 12539

Abstract

Sialidosis (MIM 256550) is a rare, autosomal recessive inherited disorder, caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. This genetic alteration leads to abnormal intracellular accumulation as well as urinary excretion of sialyloligosaccharides. A definitive diagnosis is made after the identification of a mutation in the NEU1 gene. So far, 40 mutations of NEU1 have been reported. An association exists between the impact of the individual mutations and the severity of clinical presentation of sialidosis. According to the clinical symptoms, sialidosis has been divided into two subtypes with different ages of onset and severity, including sialidosis type I (normomorphic or mild form) and sialidosis type II (dysmorphic or severe form). Sialidosis II is further subdivided into (i) congenital; (ii) infantile; and (iii) juvenile. Despite being uncommon, sialidosis has enormous clinical relevance due to its debilitating character. A complete understanding of the underlying pathology remains a challenge, which in turn limits the development of effective therapeutic strategies. Furthermore, in the last few years, some atypical cases of sialidosis have been reported as well. We herein attempt to combine and discuss the underlying molecular biology, the clinical features, and the morphological patterns of sialidosis type I and II. Full article

(This article belongs to the Special Issue Diagnosis and Management of Pediatric Diseases)

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