General description

Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive neutral lipid storage disorder caused by mutations in the ABHD5 gene (also known as CGI-58), located on chromosome 3p21 . The ABHD5 gene encodes a protein that serves as a cofactor for adipose triglyceride lipase (ATGL), which is essential for the breakdown of triglycerides into fatty acids for cellular energy metabolism .

Mutations in the ABHD5 gene impair the protein's ability to activate the ATGL enzyme, resulting in defective lipolysis activity in multiple tissue cells . This dysfunction leads to the systemic accumulation of triglycerides in cytoplasmic lipid droplets throughout various organs and tissues, including the skin, liver, muscles, intestine, bone marrow, and central nervous system .

Clinical manifestations

The clinical phenotype of Chanarin-Dorfman syndrome is highly heterogeneous and involves multiple organ systems . The most consistent feature is congenital ichthyosis, typically presenting as non-bullous congenital ichthyosiform erythroderma with fine white scaling .

Hepatic involvement is observed in more than 80% of patients, ranging from hepatomegaly and liver steatosis to cirrhosis and liver failure . Myopathy typically manifests in adulthood, usually beginning in the 30s, with progressive muscle weakness and abnormal electromyography findings .

Ocular manifestations include cataracts and keratopathy, while sensorineural hearing loss affects approximately 30% of patients . Additional systemic features may include short stature, growth retardation, intellectual disabilities, and in some cases, cardiomyopathy.

MR spectroscopy

Single-voxel 1H-MR spectroscopy demonstrates characteristic lipid peaksat 1.3ppm and 0.9ppm in white matter regions, indicating abnormal triglyceride storage .

References

1. Huigen, Marleen CDG, et al. "Cerebral lipid accumulation in Chanarin–Dorfman syndrome." Molecular genetics and metabolism 114.1 (2015): 51-54.