Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations

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• 作者：Soo Yeon Kim ; Sun Ah Choi ; Sangmoon Lee ; Jin Sook Lee ; Che Ry Hong ; Byung Chan Lim ; Hyoung Jin Kang ; Ki Joong Kim ; Sung-Hye Park ; Murim Choi and Jong-Hee Chae
• 刊名：American Journal of Medical Genetics Part A
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：170
• 期：11
• 页码：3023-3027
• 全文大小：1032K
• ISSN：1552-4833

文摘

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.