|Disease group||Keratinization Disorder|
|DISEASE NAME||Chanarin-Dorfman syndrome|
|Synonymous||Neutral lipid storage disease with ichthyosis, Triglyceride storage disease with impaired long-chain fatty acid oxidation, Ichthyotic neutral lipid storage disease, Dorfman-Chanarin syndrome, Chanarin-Dorfman disease, Ichthyosiform erythroderma with leukocyte vacuolation|
|Gene (s)||ABHD5 (CGI58, NCIE2) (604780)|
Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder of lipid metabolism characterized by multisystemic intracellular accumulation of triglycerides although plasma concentrations are normal. Clinical signs are variable and include ichthyosis, hepatomegaly, myopathy, cataracts and neurosensory deafness. It is a very rare disease mainly reported in consanguineous families from the Middle-East. It is caused by mutations in the ABHD5 gene.
The clinical presentation is variable due to multisystemic involvement. CDS infants typically present with generalized ichthyosiform erythroderma at birth, with small, whitish scales. Collodion babies have been reported. Later, the face can be taut. Scales can be larger and thicker. Hyperkeratosis of palms and soles is frequent. Patients resemble mild to moderately severe non-bullous congenital ichthyosiform erythroderma.Hepatomegaly is often noticed on physical examination. The myopathy may be subtle. Muscle creatine phosphokinase (CPK) can be elevated. Neurological impairment is also variable. Developmental delay and mild mental retardation are the most frequent findings. Cataracts are the most frequent ocular signs. Mild ectropion is frequent. However, systemic manifestations of NLSD may be clinically absent in infants, young children and even older patients.
Intracellular triglyceride metabolism is abnormal, with triglyceride accumulation in leukocytes, macrophages and fibroblasts. CDS is due to mutations in the ABHD5 gene (also named CGI-58) on 3p25.3-p24.3. ABHD5 encodes the abhydrolase domain-containing protein 5, a protein with homology to the esterase/lipase/thioesterase subfamily. Its precise function in intracellular glyceride metabolism is unknown. The recycling of triglyceride-derived mono-or diacylglycerols into specific phospholipids is abnormal, altering the synthesis and degradation of cellular phospholipids.
The diagnosis of CDS is based on the presence of lipid-containing vacuoles in circulating granulocytes, eosinophiles and monocytes on peripheral blood smear. Using oil red-O, histological skin examination shows lipid droplets in the basal and granular cell layers, in sweat glands and in ducts. Liver and muscle biopsy can show fatty changes.
The phenotype is markedly variable, and the treatment should be adapted to each patient's manifestations. Systemic retinoids can be useful for severe skin manifestations. The usefulness of fat-restricted diets is uncertain. The prognosis of CDS depends mainly upon the severity of hepatic involvement.