Atypical presentation of infantile‐onset farber disease with novel ASAH1 mutations. Issue 11 (13th July 2016)

• Record Type: Journal Article
• Authors: Kim, Soo Yeon; Choi, Sun Ah; Lee, Sangmoon; Lee, Jin Sook; Hong, Che Ry; Lim, Byung Chan; Kang, Hyoung Jin; Kim, Ki Joong; Park, Sung‐Hye; Choi, Murim; Chae, Jong‐Hee
• Is Part Of: American journal of medical genetics. Volume 170:Issue 11(2016)
• Page Start: 3023
• Page End: 3027
• Publication Date: 2016-07-13
• Subjects: farber disease -- farber lipogranulomatosis -- ASAH1 -- whole‐exome sequencing; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37846
• Languages: English
• ISSNs: 1552-4825

Abstract

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.