Chanarin‐Dorfman Syndrome: A comprehensive review

Abstract

Chanarin-Dorfman syndrome (CDS) is an extremely rare, multisystemic, autosomal recessive, neutral lipid storage disease (NLSD). It was first observed by Jordan in 1953, who identified lipid vacuoles in the cytoplasm of leukocytes from the peripheral blood smear of 2 brothers who suffered from progressive muscular dystrophy. 1 Two decades later, Dorfman in 1974 and Chanarin in 1975 reported for the first time a neutral lipid storage disease characterized by lipid accumulation in the peripheral blood leukocytes, bone marrow granulocyte precursors, liver cells and many other cells in the body. 2,3 To date, approximately 120 cases of CDS have been reported around the world. The syndrome is caused by the mutation of the abhydrolase domain containing 5 (ABHD5) gene, also called the comparative gene identification-58 (CGI-58) gene, located on the 3p21 chromosome. The product of this gene is a member of the large α/β-hydrolase family of proteins with 349 amino acids and a molecular mass of approximately 39 kD that enables the activation of adipose triglyceride lipase (ATGL) which plays and important role in intracellular lipolysis. Mutation of the ABHD5 gene results in the total or partial inactivation of the ATGL enzyme that enables the release of fatty acids (FAs) from the intracellular triacylglycerol (TG) stores of adipose and nonadiposetissues. This leads to insufficient FA mobilization within the cell, which in turn causes the accumulation of intracytoplasmic lipid droplets that contain TG. 4,5 These lipid droplets have been observed in hepatocytes, intestinal mucosa, blood, bone marrow, skin fibroblasts, myocytes, central nervous system cells and many other types of cells. CDS is associated with a multitude of clinical symptoms, the most prominent of which are non-bullous congenital ichthyosiform erythroderma and liver steatosis, whereas others include splenomegaly, myopathy, sensorineural hearing loss, nystagmus, ataxia, cataract, mental retardation and growth retardation. These clinical symptoms tend to vary according to the patients' ethnic origin and the different mutations they have. The diagnosis is based on the presence of ichthyosis and identification of lipid droplets in granulocytes (Jordan's anomaly) in peripheral blood smear. 6,7

Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases—Review Article

“…ABHD5 is a co-activator of the hydrolase activity of ATGL. Lipid droplets can be observed in several tissues, which indeed reflects the multiorganic character of Dorfman-Chanarin syndrome, which includes, i.e., hepatomegaly and muscle weakness ( 99 , 100 ).…”

“…In humans, mutations in the ABHD5 gene cause rare, multisystemic Dorfman-Chanarin syndrome (neutral lipid storage disease-NLSD) ( 99 , 100 ). One of the characteristic (and diagnostic) features of this disease is the presence of ichthyosis and lipid droplets in granulocytes.…”

Genetics: A new clinical tool for the hepatologist

“…Moving from genetic cholestatic to FLD, the clinical features and the genotype–phenotype correlations of mutations of the abhydrolase domain containing 5 ( ABHD5 ) gene, encoding for an essential cofactor of triglyceride hydrolases in hepatocytes and responsible for Chanarin–Dorfman syndrome have also been reviewed in the journal 15 …”

Case Report: Chanarin-Dorfman Syndrome: A Novel Homozygous Mutation in ABHD5 Gene in a Chinese Case and Genotype-Phenotype Correlation Analysis

“…Other manifestations include liver steatosis, myopathy, sensoryneural hearing loss, and cataract ( Yamaguchi and Osumi, 2009 ). To date, approximately 120 cases of CDS have been reported around the world, but mainly in Mediterranean and Middle Eastern countries, especially in Turkey ( Incecik et al, 2018 ; Eskiocak et al, 2019 ; Louhichi et al, 2019 ; Niculescu et al, 2019 ; Al-Hage et al, 2020 ; Dabas et al, 2020 ; Cakmak and Bagci, 2021 ; Jiang et al, 2021 ; Tavian et al, 2021 ). So far, only three patients of CDS have been reported from China ( Takeichi et al, 2016 ; Jiang et al, 2021 ).…”