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Galactosialidosis
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
That the primary defect was not in sialidase was shown by complementation of the cells of patients with sialidosis by hybridization with cells of patients with the combined defect [11, 13]. Further, in the combined defect cells, both enzyme defects could be restored by a glycoprotein corrective factor produced in culture by normal fibroblasts or those of β-galactosidase deficiency indicating the presence of a third protein acting as a corrective factor. The turnover of β-galactosidase in normal fibroblasts was 10 days, while in the cells deficient in both enzymes it was less than one day [14] and, in experiments with purified enzyme, it was clear that the rapid turnover was caused by proteolytic degradation of the enzyme [15, 16]. The disorder was named galactosialidosis in 1981 [17]. The molecular defect was found by d'Azzo and colleagues [16] to be in the PPCA, which aggregates with both enzymes to form multimers that resist lysosomal degradation. The gene has been mapped to chromosome 20q13.1 [18, 19], and the human cDNA has been cloned [20]. Mutations have been discovered [21, 22]. The number of patients reported has been small, the majority in the juvenile or adult variants.
Heterozygous structural variation mimicking homozygous missense mutations in NEU1 associated with presenting clinical signs in eyes alone
Published in Ophthalmic Genetics, 2020
At present, cherry-red spots have been described in eleven diseases where mutations in nine genes have been reported to be responsible for nine autosomal recessive diseases (Table 1), including sialidosis caused by NEU1 mutations. Sialidosis due to NEU1 mutations is characterized by myoclonus (100%), ataxia (87.8%), seizure (73.7%), and cherry-red spots of the maculae (51.2%) (10). This disease can be subdivided based on the severity of the clinical manifestations and the age of onset. The prevalence of sialidosis is approximately 1:2,200,000 in live births (11). Sialidosis type I, also known as cherry-red spot-myoclonus syndrome, is a late-onset and milder type with progressive myoclonic epilepsy, visual impairment and ataxia in adolescence. Sialidosis type II has an earlier onset and with a more severe phenotype that can include hepatomegaly, coarse facial features, intellectual disability, and dysostosis multiplex. Among patients with cherry-red spots due to NEU1 mutations, 89% of patients were classified as sialidosis type I while 11% were classified as sialidosis type II. However, isolated ocular signs as the presenting manifestation are rare, although a cherry-red spot is common in patients with sialidosis (4,12,13).
New discoveries in progressive myoclonus epilepsies: a clinical outlook
Published in Expert Review of Neurotherapeutics, 2018
Shweta Bhat, Subramaniam Ganesh
Type I sialidosis is often suspected when there is typical myoclonus along with ophthalmological problems and the characteristic cherry-red spot formation. Laboratory testing for sialyl oligosacchariduria is also an indicative diagnostic test. However, due to its less severe form and normomorphic features, the normal intelligence, and longer survival, type I sialidosis is often challenging to suspect. In contrast, type II sialidosis is severe, occurring with distinguishable phenotypic characteristics, such as dysmorphism, severe cortical myoclonus along with other symptoms, such as acites, hepato/splenomegaly is quite straightforward to be diagnosed. Very recently, spectral domain optical coherence tomography (SD-OCT) was used in macular scan for the presence of cherry red spot and ganglion cell damage in a suspected patient of sialidosis with PME. SD-OCT has been proposed to be a tool for differential diagnosis and follow up of neurological metabolic disorders [109]. Ultimately, biochemical testing for neuraminidase activity, accompanied by a genetic test for the pathogenic mutation in the NEU1 gene, is the confirmatory diagnostics [102,105,110].