The Clinical and Molecular Spectrum of GM1 Gangliosidosis.

Autor: Arash-Kaps L; Villa Metabolica, Department of Pediatric and University Medical Center Mainz, Germany., Komlosi K; Adolescent Medicine, and Institute of Human Genetics, University Medical Center Mainz, Germany., Seegräber M; Villa Metabolica, Department of Pediatric and University Medical Center Mainz, Germany., Diederich S; Adolescent Medicine, and Institute of Human Genetics, University Medical Center Mainz, Germany., Paschke E; University Children's Hospital Graz, Austria., Amraoui Y; Villa Metabolica, Department of Pediatric and University Medical Center Mainz, Germany., Beblo S; Department of Women and Child Health, Hospital for Children and Adolescents, Centre for Paediatric Research Leipzig (CPL), University Hospitals, University of Leipzig, Leipzig., Dieckmann A; Center for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena., Smitka M; Neuropediatric Department, Carl Gustav Carus University Children's Hospital Dresden, Germany., Hennermann JB; Villa Metabolica, Department of Pediatric and University Medical Center Mainz, Germany.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2019 Dec; Vol. 215, pp. 152-157.e3.
DOI: 10.1016/j.jpeds.2019.08.016
Abstrakt: Objective: To evaluate the clinical presentation of patients with GM1 gangliosidosis and to determine whether specific clinical or biochemical signs could lead to a prompt diagnosis.
Study Design: We retrospectively analyzed clinical, biochemical, and genetic data of 22 patients with GM1 gangliosidosis from 5 metabolic centers in Germany and Austria.
Results: Eight patients were classified as infantile, 11 as late-infantile, and 3 as juvenile form. Delay of diagnosis was 6 ± 2.6 months in the infantile, 2.6 ± 3.79 years in the late-infantile, and 14 ± 3.48 years in the juvenile form. Coarse facial features, cherry red spots, and visceromegaly occurred only in patients with the infantile form. Patients with the late-infantile and juvenile forms presented with variable neurologic symptoms. Seventeen patients presented with dystonia and 14 with dysphagia. Laboratory analysis revealed an increased ASAT concentration (13/20), chitotriosidase activity (12/15), and pathologic urinary oligosaccharides (10/19). Genotype analyses revealed 23 causative or likely causative mutations in 19 patients, 7 of them being novel variants. In the majority, a clear genotype-phenotype correlation was found.
Conclusions: Diagnosis of GM1 gangliosidosis often is delayed, especially in patients with milder forms of the disease. GM1 gangliosidosis should be considered in patients with progressive neurodegeneration and spastic-dystonic movement disorders, even in the absence of visceral symptoms or cherry red spots. ASAT serum concentrations and chitotriosidase activity may be of value in screening for GM1 gangliosidosis.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: