Liver cirrhosis in an infant with Chanarin–Dorfman syndrome caused by a novel splice-site mutation in ABHD5 M Cakir (muratcak@hotmail.com) 1 , C Bruno 2 , A Cansu 3 , U Cobanoglu 4 , E Erduran 5 1.Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University, Trabzon, Turkey 2.Muscular and Neurodegenerative Disease Unit, Giannina Gaslini Institute, University of Genova, Genova, Italy 3.Department of Radiology, Karadeniz Technical University, Trabzon, Turkey 4.Department of Pathology, Karadeniz Technical University, Trabzon, Turkey 5.Department of Pediatric Hematology, Karadeniz Technical University, Trabzon, Turkey Keywords Chanarin-Dorfman syndrome, Fatty liver disease, Infancy, Liver cirrhosis Correspondence M Cakir, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karadeniz Technical University, Trabzon, Turkey. Tel: +90 5326 810318 | Fax: +90 4623 7758 90 | Email: muratcak@hotmail.com Received 17 January 2010; revised 16 March 2010; accepted 5 May 2010. DOI:10.1111/j.1651-2227.2010.01869.x ABSTRACT We described a Turkish girl with Chanarin–Dorfman syndrome who developed liver cirrho- sis in the early infancy. She had all the clinical features of Chanarin–Dorfman syndrome such as ichthyosis, Jordan’s anomaly, fatty liver disease and mild ectropion. The diagnosis was confirmed with a novel ABHD5 mutation. Liver steatosis or steatohepatitis with or with- out hepatomegaly is the predominant finding of Chanarin–Dorfman syndrome. Cirrhosis has been reported in patients with long-duration disease. Conclusion: Local factors or dysfunction of local proteins such as mutations or polymorphisms in hepatic microsomal lipase and arylacetamide deacetylase may contribute the severity of liver involvement, and steatosis may progress to cirrhosis in the early infancy in Chanarin–Dorfman syndrome. INTRODUCTION Paediatric non-alcoholic fatty liver disease (NAFLD) is increasingly being diagnosed with the current worldwide epidemic of paediatric overweight ⁄ obesity (1,2). Apart from obesity; some genetic diseases may present with NAFLD. Some of these are Alstro ¨ m syndrome, Cantu syndrome, Mulibrey nanism and Chanarin–Dorfman syndrome (CDS) (2). CDS is rare non-lysosomal and autosomal recessive dis- order associated with congenital ichthyosis and accumula- tion of triacylglycerol in the cytoplasmic lipid droplets in various types of cells. The diagnosis is based on the clinical and histochemical features (3). Herein, we describe a child with cirrhosis with CDS bear- ing a novel ABHD5 mutation. CASE REPORT A 2 years 2 months (2 2 ⁄ 12 -year)-old girl was referred for ele- vated liver enzymes for 2 months. She was born at term from consanguineous marriage. She had scaly skin at birth, but no evidence of any definite collodion membrane. She followed by dermatology unit for ichthyosis since birth and biopsy revealed lamellar ichthyosis and was prescribed topi- cal moistures. Her father and grandfather had minor com- plaints about skin. On physical examination, her weight and height were 25th and 50th percentiles, respectively. Mild erythema and desquamation on entire body surface were detected. Hyper- keratosis was marked on palms, soles, at elbows, knees and ankles. There was mild lateral ectropion of the lower eyelids (Fig. S1a,b,c). Liver was palpated 2 cm below the costal margin. Neurological examination was normal. Laboratory investigation showed normal blood count, electrolytes, protein, cholesterol and other lipid levels. Serum AST, ALT, GGT, bilirubine and CPK levels were 65 U ⁄ L, 87 U ⁄ L, 16 U ⁄ L, 0.2 mg ⁄ dL and 322 U ⁄ L, respec- tively. Coagulation parameters, alpha-fetoprotein, carnitine, bile acid and immunoglobulin levels were within normal limits. Viral serology was negative. Organic acid and tandem mass spectrometry were normal. Abdominal ultrasound revealed steatosis. FibroScan Ò (Echosens, Paris, France) score was 21 kPa. Electromyography was normal. Hyperintense non-specific lesions were seen in the subcorti- cal white matter in T2-weighed images. Other cranial structures were normal. Peripheral smear examination revealed cytoplasmic vacu- oles within the granulocytes, eosinophiles and monocytes (Fig. S2). Liver biopsy was performed and revealed grade 3 microvesicular and macrovesicular steatosis, and steatohep- atitis associated with nodule formation (Fig. S3a,b). A diagnosis of CDS was made based on dermatologi- cal, peripheral smear and liver biopsy findings. After obtaining informed consent from the parents, DNA was purified from the peripheral blood leucocytes of the patient and parents. Mutation analysis of the CGI-58 gene was studied as defined elsewhere (3). We found a novel homozygous splice-site mutation (IVS + 1G>A) (Fig. S4). A low fat diet supplemented with medium-chain fatty acids (MFA) was recommended. Ursodeoxycholic acid (UDCA) (20 mg ⁄ kg) and vitamin E (100 U ⁄ day) Liver cirrhosis in an infant with Chanarin–Dorfman syndrome Cakir et al. 1592 ª2010 The Author(s)/Journal Compilation ª2010 Foundation Acta Pædiatrica/Acta Pædiatrica 2010 99, pp. 1592–1594