An Adolescent with Chanarin-Dorfman Syndrome Presenting with Ichthyosis and Hepatic Steatosis

“

TL;DR

Chanarin-Dorfman syndrome (CDS) is a rare genetic disorder causing ichthyosis and fatty liver disease. This case describes a 10-year-old boy with CDS whose liver enzymes improved on a high-MCT diet and vitamin E, but worsened with acitretin for ichthyosis. Clinicians should suspect CDS in lean patients with nonalcoholic steatohepatitis and ichthyosis, especially those of Middle Eastern ancestry.

Full summary

3,141 CHARS

**Background:** Chanarin-Dorfman syndrome (CDS), also known as neutral lipid storage disease, is a rare autosomal recessive disorder with fewer than 100 reported cases. It is most common in individuals of Mediterranean and Middle Eastern origin. CDS results from mutations in the ABHD5 gene on chromosome 3, leading to dysfunction of adipose triglyceride lipase and impaired triglyceride metabolism. The condition is characterized by ichthyosis, liver involvement, and developmental delay. This case report describes a 10-year-old Kurdish male with CDS who presented with ichthyosis and elevated transaminases.

**Methods:** The patient was referred to the pediatric liver clinic at age 10 for evaluation of new-onset transaminase elevation (ALT 171 U/L, normal <55 U/L; AST 103 U/L, normal <60 U/L). He was born to consanguineous Iraqi Kurdish parents. Workup included viral serologies, celiac disease testing, thyroid function, metabolic studies (serum amino acids, urinary organic acids, transferrin isoelectric focusing, carnitine and acyl-carnitine profile), complete blood count with peripheral smear, abdominal ultrasound, liver biopsy, FibroScan, and genetic testing using a congenital ichthyosis gene panel (XomeDxSlice, Genedx).

**Key Results:** The patient had a lean body habitus (BMI 20.12 kg/m², 88th percentile). Physical exam revealed diffuse ichthyosis, erythroderma, cerumen impaction, a systolic murmur, and hepatomegaly (5.5 cm below costal margin). Neuropsychiatric assessment was normal except for anxiety and depression. Laboratory findings included elevated creatine kinase (1048 U/L, normal <198 U/L) and Jordan's anomaly (vacuolated granulocytes on peripheral smear). Abdominal ultrasound showed hepatic steatosis. Liver biopsy demonstrated mild (25%) macrovesicular steatosis, chronic lymphocytic inflammation, and focal zone 3 perisinusoidal and pericellular fibrosis (stage 1 of 4). FibroScan at age 10 showed stage 2 fibrosis with a median liver stiffness of 8.7 kPa. Genetic testing identified a homozygous mutation c.776G>A (p.G259D) in the ABHD5 gene, a known cause of CDS. At age 12, repeat FibroScan showed advanced fibrosis (median stiffness 16.5 kPa). The patient was started on vitamin E 400 IU twice daily and a diet with a high medium-chain triglyceride (MCT) to long-chain triglyceride (LCT) ratio. Acitretin (10 mg/day) was initiated for ichthyosis but led to worsening transaminases and bilirubin, requiring discontinuation. After dietary intervention and vitamin E, liver enzymes improved.

**Clinical Implications:** CDS should be considered in lean patients with nonalcoholic steatohepatitis (NASH) and ichthyosis, particularly those of Middle Eastern ancestry. Management requires a multidisciplinary approach. Dietary modification with a high MCT/LCT ratio and vitamin E may improve hepatic steatosis. Systemic retinoids like acitretin can cause drug-induced liver injury in CDS patients, necessitating close monitoring of liver biochemical profile. This case highlights the importance of genetic testing for ABHD5 mutations in patients with unexplained transaminase elevation and ichthyosis.