Chanarin-Dorfman syndrome

Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability.

The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome. Some people may have ichthyosis only, while others may have problems affecting many areas of the body.

Chanarin-Dorfman syndrome is a rare condition; its incidence is unknown.

Mutations in the ABHD5 gene cause Chanarin-Dorfman syndrome. The ABHD5 gene provides instructions for making a protein that turns on (activates) the ATGL enzyme, which breaks down triglycerides. Triglycerides are the main source of stored energy in cells. These fats must be broken down into simpler molecules called fatty acids before they can be used for energy.

ABHD5 gene mutations impair the protein's ability to activate the ATGL enzyme. An inactive enzyme makes the breakdown of triglycerides impossible, causing them to accumulate in tissues throughout the body. The buildup of triglycerides results in the signs and symptoms of Chanarin-Dorfman syndrome.

Genetic Testing Information

• Genetic Testing Registry: Triglyceride storage disease with ichthyosis

Genetic and Rare Diseases Information Center

• Neutral lipid storage disease with ichthyosis

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• CHANARIN-DORFMAN SYNDROME; CDS

Scientific Articles on PubMed

• PubMed

• Bruno C, Bertini E, Di Rocco M, Cassandrini D, Ruffa G, De Toni T, Seri M, Spada M, Li Volti G, D'Amico A, Trucco F, Arca M, Casali C, Angelini C, Dimauro S, Minetti C. Clinical and genetic characterization of Chanarin-Dorfman syndrome. Biochem Biophys Res Commun. 2008 May 16;369(4):1125-8. doi: 10.1016/j.bbrc.2008.03.010. Epub 2008 Mar 11. Citation on PubMed
• Bruno C, Dimauro S. Lipid storage myopathies. Curr Opin Neurol. 2008 Oct;21(5):601-6. doi: 10.1097/WCO.0b013e32830dd5a6. Citation on PubMed
• Elias PM, Williams ML, Holleran WM, Jiang YJ, Schmuth M. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J Lipid Res. 2008 Apr;49(4):697-714. doi: 10.1194/jlr.R800002-JLR200. Epub 2008 Feb 2. Citation on PubMed or Free article on PubMed Central
• Lass A, Zimmermann R, Haemmerle G, Riederer M, Schoiswohl G, Schweiger M, Kienesberger P, Strauss JG, Gorkiewicz G, Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 2006 May;3(5):309-19. doi: 10.1016/j.cmet.2006.03.005. Citation on PubMed
• Lefevre C, Jobard F, Caux F, Bouadjar B, Karaduman A, Heilig R, Lakhdar H, Wollenberg A, Verret JL, Weissenbach J, Ozguc M, Lathrop M, Prud'homme JF, Fischer J. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am J Hum Genet. 2001 Nov;69(5):1002-12. doi: 10.1086/324121. Epub 2001 Oct 2. Citation on PubMed or Free article on PubMed Central
• Pujol RM, Gilaberte M, Toll A, Florensa L, Lloreta J, Gonzalez-Ensenat MA, Fischer J, Azon A. Erythrokeratoderma variabilis-like ichthyosis in Chanarin-Dorfman syndrome. Br J Dermatol. 2005 Oct;153(4):838-41. doi: 10.1111/j.1365-2133.2005.06828.x. Citation on PubMed