P78 – 2554: Farber disease in a child with a novel homozygous c.92G>T mutation

Abstract

Objective Farber disease is an extremely rare autosomal recessive lysosomal storage disease marked by a deficiency in enzyme acid ceramidase that causes an accumulation of fatty material lipids leading to abnormalities in the joints, liver, throat, tissues and central nervous system. To date, less than 25 distinct mutations have been identified in farber patients, but no homozygous c.92G>T mutation have yet been reported. Methods A five-month-old male presented at our institution with a hoarse cry, irritability and weak head control. His physical examination revealed coarse facial appearance, joint stiffness, axial hypotonia and hepatomegaly. Ophtalmoscopic examination revealed macular cherry-red spots. Serebral magnetic resonance imaging (MRI) was consistent with communicating hydrocephalus at six months of age. Serebral and servical spinal MRI revealed noduler soft tissue extension that involved cervicomeduller junction at the atlantoaxial level at eight months of age. There were multiple subcutaneous nodules measuring 0.5 to 1 cm in diameter over the interphalangeal joints of the hand appeared at the age of 16 months. There were no evidence of urine mucopolysaccharide or oligosaccharide screen. Urinary sialic acid were normal. Through the analysis of lysosomal enzymes activities revealed normal. The plasma chitotriosidase was raised 3654umol/lhr, (normal of 4–120). The diagnosis of Farber lipogranulomatosis was suggested and gene sequencing of the ASAH1 gene confirmed the diagnosis of Farber disease Results A homozygous c.92G> T mutation was found in our patient. Conclusion Farber lipogranulomatosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the ASAH1 gene. To the best of our knowledge, this is the first report of a novel homozygous c.92G> T mutation in ASAH1 gene which is associated with Farber disease