Sialidoses (Types I and II)

Franceschetti, S.; Canafoglia, Laura; Panzica, Ferruccio

doi:10.1007/978-1-84882-128-6_183

Cited by 3 publications

(5 citation statements)

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“…NEU1 is a lysosomal sialidase (EC 3.2.1.18) that cleaves the terminal sialic acid in oligosaccharide chains. Decreased NEU1 activity results in the accumulation of sialoglycoconjugates in cells and tissues, leading to various symptoms such as visual impairment, myoclonus, ataxia, seizure, mental retardation and hepatosplenomegaly [1][2][3][4]. Sialidosis is classified into two clinical variants with different onset and severity: Type I is a relatively mild form with infantile onset, while type II is an early-onset form with more severe manifestations.…”

Section: Introductionmentioning

confidence: 99%

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cells obtained from a Patient with Sialidosis

Davaadorj¹,

Akatsuka²,

Yamaguchi³

et al. 2017

Cell Dev Biol

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Sialidosis type I patient-derived induced pluripotent stem cells (iPSCs) were generated from blood mononuclear cells. During embryoid body-like 3D culture, aggregates of patient-derived iPSCs were irregular in shape and had increased vacuoles filled with lipid droplets and cellular components such as damaged mitochondria. Retinal pigment epithelial cells induced from patient-derived iPSCs showed impaired autophagy flux with decreased formation of LC3 puncta. Sialidosis patient-derived iPSCs could provide a useful tool for investigating the mechanism of the autophagy/ lysosome-mediated degradation system.

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Section: Introductionmentioning

confidence: 99%

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cells obtained from a Patient with Sialidosis

Davaadorj¹,

Akatsuka²,

Yamaguchi³

et al. 2017

Cell Dev Biol

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“…Clinical phenotype correlates closely with the type of NEU1 mutations and the levels of residual enzyme activity. [4][5][6] Type 2 sialidosis is the severe form that has 3 subtypes: congenital with onset in utero, infantile with onset between birth and 12 months, and juvenile with onset after 2 years of age. Babies with congenital form of the disease develop hydrops fetalis, neonatal ascites, inguinal hernias, and hepatosplenomegaly.…”

mentioning

confidence: 99%

“…Life expectancy varies based on genotype and phenotypic severity; however, most patients become wheelchair-bound within few years due to severe myoclonus causing motor deterioration. [4][5][6] Neuropathologic features include vacuolations with neuronal intracytoplasmic lipofuscin-like pigment storage seen in the neocortex, basal ganglia, thalamus, brainstem, and spinal cord. No abnormalities are seen on brain MRI in early stages of the disease whereas atrophy of the cerebral cortex, pons, and cerebellum may be seen during progression.…”

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confidence: 99%

“…No abnormalities are seen on brain MRI in early stages of the disease whereas atrophy of the cerebral cortex, pons, and cerebellum may be seen during progression. 5 Diagnosis is usually suggested by increased urinary excretion of sialic acid. Confirmation is by demonstrating enzyme deficiency in cultured fibroblasts or genetic testing.…”

mentioning

confidence: 99%

“…Confirmation is by demonstrating enzyme deficiency in cultured fibroblasts or genetic testing. 4,5 Current pharmacologic management involves treating the myoclonic epilepsy. Antiepileptics that have been used include valproic acid, levetiracetam, phenobarbital, zonisamide, and benzodiazepines.…”

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confidence: 99%

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Child Neurology: Type 1 sialidosis due to a novel mutation in NEU1 gene

et al. 2018

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A 39-year-old man of Ecuadorian descent presented with a history of seizures, visual impairment, and ataxia. He had a normal birth and early developmental history. His first seizure was a generalized tonic-clonic seizure (GTCS) at 16 years old. Around the same time, he also started experiencing 1-2 myoclonic jerks per day. The myoclonic jerks progressively worsened over a period of 20 years to 15-20 episodes per day. GTCS continued to occur 1-2 times a year until the age of 24 years. EEG revealed multiple brief myoclonic seizures and generalized slow spike/polyspike wave complexes consistent with primary generalized epilepsy. Despite valproic acid, zonisamide, and clonazepam, his seizure control remained poor. When he was 30 years old, he began to have blurring of his vision; ophthalmologic evaluation at that time revealed bilateral cherry-red spots. Optical coherence tomography showed hyperreflectivity in the superficial layers of the retina at the posterior pole consistent with abnormal storage in the ganglion cells. An electroretinogram showed normal rod and cone responses. Flash visual evoked responses demonstrated a delay in the P100 response consistent with dysfunction of the visual pathways. His medical and family history was otherwise noncontributory. Gross physical examination was within normal limits. Neurologic examination demonstrated severe myoclonus of the face interrupting his speech, frequent myoclonus of the arms, truncal and appendicular ataxia, and broad-based ataxic gait. MRI of the brain with and without gadolinium was normal. Chromosome single nucleotide polymorphism microarray revealed long contiguous regions of allele homozygosity (>10 MB) in multiple chromosomes. A query of the regions of homozygosity that was subsequently narrowed down using his clinical presentation identified NEU1 as a candidate gene. Sequencing of NEU1 revealed a homozygous missense mutation c.629C>T (p.Pro210Leu). Enzymatic testing in fibroblasts showed sialidase activity to be deficient (0 nmol/h/mg; ref: 23-74). β-Galactosidase activity was within normal limits.

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Clinical Development of Cell Therapies to Halt Lysosomal Storage Diseases: Results and Lessons Learned

Graceffa

2022

CGT

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: Although cross-correction was discovered more than 50 years ago, and held the promise of drastically improving disease management, still no cure exists for lysosomal storage diseases (LSDs). Cell therapies hold the potential to halt disease progression: either a subset of autologous cells can be ex vivo/ in vivo transfected with the functional gene or allogenic wild type stem cells can be transplanted. However, majority of cell-based attempts have been ineffective, due to the difficulties in reversing neuronal symptomatology, in finding appropriate gene transfection approaches, in inducing immune tolerance, reducing the risk of graft versus host disease (GVHD) when allogenic cells are used and that of immune response when engineered viruses are administered, coupled with a limited secretion and uptake of some enzymes. In the last decade, due to advances in our understanding of lysosomal biology and mechanisms of cross-correction, coupled with progresses in gene therapy, ongoing pre-clinical and clinical investigations have remarkably increased. Even gene editing approaches are currently under clinical experimentation. This review proposes to critically discuss and compare trends and advances in cell-based and gene therapy for LSDs. Systemic gene delivery and transplantation of allogenic stem cells will be initially discussed, whereas proposed brain targeting methods will be then critically outlined.

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Sialidoses (Types I and II)

Cited by 3 publications

References 12 publications

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cells obtained from a Patient with Sialidosis

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cells obtained from a Patient with Sialidosis

Child Neurology: Type 1 sialidosis due to a novel mutation in NEU1 gene

Clinical Development of Cell Therapies to Halt Lysosomal Storage Diseases: Results and Lessons Learned

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