Chanarin-Dorfman syndrome: a case report with novel mutation in ABHD5 gene

α/β-hydrolase domain-containing protein 5 (ABHD5) is a lipid droplet-associated protein that promotes the hydrolysis of triacylglycerols (TAGs) by activating adipose triglyceride lipase (ATGL). ATGL is a lipase that c atalyzes the initial and rate-limiting step in lipolysis by removing the first fatty acid from TAGs. ABHD5 gene mutations in humans lead to Chanarin–Dorfman syndrome (CDS), a rare condition in which TAGs accumulate in various tissues, including skin and liver. To date, about 40 different mutations of ABHD5 are associated with this syndrome and 15 of them result in truncated proteins. CDS is an autosomal recessive inherited neutral lipid metabolism disorder, characterized by non bullous congenital ichthyosiform erythroderma (NCIE) and variable involvement of the liver, muscles and central nervous system. Systemic involvement may manifest as hepatosplenomegaly, liver steatosis, muscle weakness, ataxia and sometimes subcapsular cataracts, nystagmus, neurosensory hearing loss and mental retardation. Here we present a 29-month-old Indian girl with NCIE, hepatosplenomegaly and diffuse hepatic steatosis that were diagnosed as CDS based on observation of lipid vacuoles (Jordan’s bodies) in granulocytes. Mutation analysis showed a novel homozygous nonsense mutation (c.297C>A) of ABHD5 gene, causing the production of a short truncated protein (p.C99X). This mutated protein loses the putative interacting domain required for ATGL activation, probably leading to an early onset of CDS in Indian patient. After the molecular confirmation of CDS diagnosis, she started a special diet, poor in fatty acids. An early initiation of a low fat diet might improve the liver condition and prevent severe systemic damages.