Early Severe Cortical Involvement and Novel FUCA1 Mutations in a Pediatric Fucosidosis Case

• Published in: Molecular genetics & genomic medicine Vol. 13; no. 2; pp. e70070 - n/a
• Main Authors: Peña, Mar Jiménez, López‐Martín, Sara, Fernández‐Mayoralas, Daniel Martín, Fernández‐Perrone, Ana Laura, Jiménez de Domingo, Ana, Tirado, Pilar, Calleja‐Pérez, Beatriz, Álvarez, Sara, Albert, Jacobo, Fernández‐Jaén, Alberto
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2025; John Wiley and Sons Inc; Wiley
• Subjects: alpha-L-Fucosidase - genetics; Atrophy; Brain; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - pathology; Child, Preschool; Clinical Report; Corpus callosum; cortical thickness; Disease; Enzymes; FUCA1 gene; Fucosidosis; Fucosidosis - diagnostic imaging; Fucosidosis - genetics; Fucosidosis - pathology; Genetic counseling; Genetic screening; Humans; Hypoplasia; Magnetic Resonance Imaging; Male; Medical imaging; Mutation; Neurodegeneration; Neuroimaging; Patients; Pediatrics; Sequences; Spasticity; Spectrum analysis; Substantia alba; Therapeutic applications; Ultrasonic imaging; Whole genome sequencing; fucosidosis; FUCA1 gene; cortical thickness; neuroimaging
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.70070

ABSTRACT Background Biallelic pathogenic variants in the FUCA1 gene are associated with fucosidosis. This report describes a 4‐year‐old boy presenting with psychomotor regression, spasticity, and dystonic postures. Methods and Results Trio‐based whole exome sequencing revealed two previously unreported loss‐of‐function variants in the FUCA1 gene. Brain magnetic resonance imaging (MRI) findings included corpus callosum hypoplasia, white matter hypomyelination, and alterations in the globus pallidi, alongside markedly reduced cortical thickness. Conclusions These findings suggest that cortical atrophy may occur in the early stages of fucosidosis. Early diagnosis is imperative for genetic counseling, timely investigations, and initiating early therapeutic interventions to potentially mitigate more extensive brain involvement. We report a 4‐year‐old boy with fucosidosis with novel pathogenic FUCA1 variants and neuroanatomical correlates. Results observed contribute to a better understanding of the genetics and pathophysiology of this rare lysosomal storage disorder.