title: Polyarticular Arthritis and Spinal Muscular Atrophy in Acid Ceramidase Deficiency.
abstract: Survival of motor neuron 1-------negative spinal muscular atrophy (SMA) is heterogeneous and remains a diagnostic challenge. The clinical spectrum continues to expand and ∼33 genes have been identified to date. The present report describes a 9-year-old girl with novel clinical phenotype of a patient with polyarticular arthritis followed by symptoms of SMA due to acid ceramidase deficiency. Whole exome sequencing identified compound heterozygous pathogenic mutation in the N-acylsphingosine amidohydrolase 1 gene. Functional assay with leukocyte acid ceramidase activity showed a decreased level in the proband confirming pathogenicity of the mutations. Mutations of N-acylsphingosine amidohydrolase 1 are known to separately cause Farber disease (arthritis, subcutaneous nodules, and dysphonia) or SMA with progressive myoclonic epilepsy. The present combined phenotype is novel, bringing together SMA with progressive myoclonic epilepsy and Farber disease and establishing a phenotypic spectrum. Acid ceramidase deficiency is an important consideration in patients presenting with polyarticular arthritis and motor neuron disease.
authors.affiliation: Departments of Neurology and.|Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: Hooi Ling
authors.initials: HL
authors.lastname: Teoh
authors.affiliation: Clinical Research, Plexcera Therapeutics LLC, New York, New York.
authors.forename: Alexander
authors.initials: A
authors.lastname: Solyom
authors.affiliation: Department of Genetic and Genomic Sciences, Icahn School of Medicine at Mt. Sinai, New York, New York.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia.|Medical Genetics, Sydney Children's Hospital, Sydney Australia.
authors.forename: David
authors.initials: D
authors.lastname: Mowat
authors.affiliation: Medical Genetics, Sydney Children's Hospital, Sydney Australia.|St Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia; and.|Kinghorn Centre for Clinical Genomics, Darlinghurst, New South Wales, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Roscioli
authors.affiliation: Departments of Neurology and.|Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Farrar
authors.affiliation: Departments of Neurology and hugo.sampaio@health.nsw.gov.au.|Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sampaio
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics*; D001171:Arthritis, Juvenile / Q000235:genetics*; D002648:Child; D055577:Farber Lipogranulomatosis / Q000150:complications / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012131:Respiratory Insufficiency / Q000209:etiology
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase