Type I sialidosis, a normosomatic lysosomal disease, in the differential diagnosis of late-onset ataxia and myoclonus: An overview.

Autor: Caciotti A; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy., Melani F; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy., Tonin R; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy., Cellai L; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy., Catarzi S; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy; Department of NEUROFARBA, University of Florence, Florence, Italy., Procopio E; Metabolic and Muscular Unit, Meyer Children's Hospital, Florence, Italy., Chilleri C; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy., Mavridou I; Division of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece., Michelakakis H; Division of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece., Fioravanti A; Structural Biology, Research Center-VIB (Flanders Interuniversity Institute for Biotechnology), University of Brussels, Belgium., d'Azzo A; Dep. of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA., Guerrini R; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy; Department of NEUROFARBA, University of Florence, Florence, Italy., Morrone A; Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, Florence, Italy; Department of NEUROFARBA, University of Florence, Florence, Italy. Electronic address: amelia.morrone@meyer.it.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2020 Feb; Vol. 129 (2), pp. 47-58. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1016/j.ymgme.2019.09.005
Abstrakt: Lysosomal storage diseases (LSDs) are rare to extremely rare monogenic disorders. Their incidence, however, has probably been underestimated owing to their complex clinical manifestations. Sialidosis is a prototypical LSD inherited as an autosomal recessive trait and caused by mutations in the NEU1 gene that result in a deficiency of alpha-N-acetyl neuraminidase 1 (NEU1). Two basic forms of this disease, type I and type II, are known. The dysmorphic type II form features LSD symptoms including congenital hydrops, dysmorphogenetic traits, hepato-splenomegaly and severe intellectual disability. The diagnosis is more challenging in the normosomatic type I forms, whose clinical findings at onset include ocular defects, ataxia and generalized myoclonus. Here we report the clinical, biochemical and molecular analysis of five patients with sialidosis type I. Two patients presented novel NEU1 mutations. One of these patients was compound heterozygous for two novel NEU1 missense mutations: c.530A>T (p.Asp177Val) and c.1010A>G (p.His337Arg), whereas a second patient was compound heterozygous for a known mutation and a novel c.839G>A (p.Arg280Gln) mutation. We discuss the impact of these new mutations on the structural properties of NEU1. We also review available clinical reports of patients with sialidosis type I, with the aim of identifying the most frequent initial clinical manifestations and achieving more focused diagnoses.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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