title: Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations.
abstract: Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole-exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole-exome sequencing for diagnosis of ultra-rare diseases. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sangmoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Che Ry
authors.initials: CR
authors.lastname: Hong
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byung Chan
authors.initials: BC
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea.
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea. chaeped1@snu.ac.kr.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics*; D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D059472:Exome; D055577:Farber Lipogranulomatosis / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase
keywords: ASAH1; farber disease; farber lipogranulomatosis; whole-exome sequencing