Laila Arash-Kaps1, Katalin Komlosi2, Marlene Seegräber1, Stefan Diederich2, Eduard Paschke3, Yasmina Amraoui1, Skadi Beblo4, Andrea Dieckmann5, Martin Smitka6, Julia B Hennermann1. 1. Villa Metabolica, Department of Pediatric and University Medical Center Mainz, Germany. 2. Adolescent Medicine, and Institute of Human Genetics, University Medical Center Mainz, Germany. 3. University Children's Hospital Graz, Austria. 4. Department of Women and Child Health, Hospital for Children and Adolescents, Centre for Paediatric Research Leipzig (CPL), University Hospitals, University of Leipzig, Leipzig. 5. Center for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena. 6. Neuropediatric Department, Carl Gustav Carus University Children's Hospital Dresden, Germany.
Abstract
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.
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.
Authors: Lazzaro di Biase; Alessandro Di Santo; Maria Letizia Caminiti; Pasquale Maria Pecoraro; Vincenzo Di Lazzaro Journal: Life (Basel) Date: 2022-01-29
Authors: Richard W D Welford; Herve Farine; Michel Steiner; Marco Garzotti; Kostantin Dobrenis; Claudia Sievers; Daniel S Strasser; Yasmina Amraoui; Peter M A Groenen; Roberto Giugliani; Eugen Mengel Journal: Mol Genet Metab Rep Date: 2022-02-01