title: Alsin related disorders: literature review and case study with novel mutations.
abstract: Mutations in the ALS2 gene cause three distinct disorders: infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and autosomal recessive juvenile amyotrophic lateral sclerosis. We present a review of the literature and the case of a 16-year-old boy who is, to the best of our knowledge, the first Portuguese case with infantile ascending hereditary spastic paraplegia. Clinical investigations included sequencing analysis of the ALS2 gene, which revealed a heterozygous mutation in exon 5 (c.1425_1428del p.G477Afs*19) and a heterozygous and previously unreported variant in exon 3 (c.145G>A p.G49R). We also examined 42 reported cases on the clinical characteristics and neurophysiological and imaging studies of patients with known ALS2 gene mutations sourced from PubMed. This showed that an overlap of phenotypic manifestations can exist in patients with infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and juvenile amyotrophic lateral sclerosis.
authors.affiliation: Department of Pediatrics, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal ; Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Flor-de-Lima
authors.affiliation: Unit of Pediatric Neurology, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Sampaio
authors.affiliation: Centogene AG, Schillingallee 68, 18057 Rostock, Germany.
authors.forename: Nahid
authors.initials: N
authors.lastname: Nahavandi
authors.affiliation: Department of Genetics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Fernandes
authors.affiliation: Unit of Pediatric Neurology, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal ; Department of Genetics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Leão