Chanarin-Dorfman syndrome is a condition in which fats (lipids) build up in the body. Affected individuals have trouble breaking down certain fats called triglycerides; these fats then accumulate in organs and tissues, including the skin, liver, muscles, intestine, and bone marrow.

People with Chanarin-Dorfman syndrome have dry, scaly skin (ichthyosis), which is usually present at birth. They may also have lower eyelids that turn out so that the inner surface is exposed (ectropion). Additional features of Chanarin-Dorfman syndrome may include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), hearing loss, short stature, progressive muscle weakness (myopathy), and intellectual disabilities. Some people with Chanarin-Dorfman syndrome develop liver failure.

The signs and symptoms of Chanarin-Dorfman syndrome can vary greatly among individuals, which can delay the diagnosis of the condition.

Several variants (also called mutations) in the ABHD5 gene have been found to cause Chanarin-Dorfman syndrome. The ABHD5 gene provides instructions for making a protein that turns on (activates) an enzyme called adipose triglyceride lipase (ATGL). This enzyme breaks down triglycerides, which are a major source of stored energy in cells. The ATGL enzyme helps break triglycerides down into simpler molecules called fatty acids, which the body can then use for energy.

ABHD5 gene variants impair the protein's ability to activate the ATGL enzyme. If there is not enough activated ATGL enzyme to break down triglycerides, these fats can accumulate in tissues throughout the body. Over time, the buildup of triglycerides can damage cells and tissues, leading to the signs and symptoms of Chanarin-Dorfman syndrome.

Normal Function

The ABHD5 gene provides instructions for making a protein that turns on (activates) an enzyme called adipose triglyceride lipase (ATGL). The ATGL enzyme plays a role in breaking down fats called triglycerides, which are a major source of stored energy in cells. Cells primarily store triglycerides in structures called lipid droplets (also called adiposomes). The ABHD5 protein and the ATGL enzyme are found on the surface of lipid droplets. Once activated, the ATGL enzyme breaks down triglycerides in these structures to provide energy for the body.

Health Conditions Related to Genetic Changes

Chanarin-Dorfman syndrome

Several variants (also called mutations) in the ABHD5 gene have been found to cause Chanarin-Dorfman syndrome, a condition in which triglycerides build up in the body. These variants impair the ABHD5 protein's ability to activate the ATGL enzyme. If there is not enough activated ATGL enzyme to break down triglycerides, these fats can accumulate in various organs and tissues throughout the body. Over time, the buildup of triglycerides can damage cells and tissues, leading to the signs and symptoms of Chanarin-Dorfman syndrome.

Other Names for This Gene

• CGI58
• comparative gene identification 58
• IECN2
• NCIE2

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Chanarin-Dorfman syndrome is a rare condition. Approximately 150 people with this condition have been reported in the literature.