title: Epidermal triglyceride levels are correlated with severity of ichthyosis in Dorfman-Chanarin syndrome.
abstract: BACKGROUND
  Dorfman-Chanarin syndrome (DCS), also referred to as neutral lipid storage disease with ichthyosis, is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma, characterized by the presence of intracellular lipid droplets in multiorgans. DCS patients often have mutations in CGI-58, which is an activator of adipose triglyceride lipase (ATGL), leading to accumulation of triglycerides (TG).
  
  
  OBJECTIVE
  To study whether a patient with DCS demonstrates TG accumulation in the epidermis and to analyze whether TG levels are correlated with skin disease activity.
  
  
  METHODS
  Skin specimen from a 62-year-old man with DCS was stained with oil red O, and analyzed on electromicrographs. Sequencing analysis of CGI-58 was performed using the patient's blood cells. The scales from the lesion were subject to lipid analysis by high-performance thin-layer chromatography (HPTLC).
  
  
  RESULTS
  The patient demonstrated ichthyoform erythroderma with a distinct seasonal fluctuation: his skin lesions were aggravated in summer but resolved during winter. Epidermis of the lesion showed intracellular lipid droplets. Sequencing analysis revealed a novel missense mutation in the exon 3 of CGI-58 gene. Lipid analysis of the scales from his lesions, compared with those from normal human control, revealed increased levels of triglycerides (TG) but, in turn, decreased levels of free fatty acids, suggesting dysfunction of adipose TG lipase. Notably, the TG levels in the scales from the patient were positively correlated with the severity of ichthyosis.
  
  
  CONCLUSIONS
  These results suggest that TG accumulation by epidermal keratinocytes directly contributes to ichthyosiform phenotype of DCS.
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Oko-cho, Nankoku, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ujihara
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Mayuko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Mika
authors.initials: M
authors.lastname: Teraishi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Uchida
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005091:Exons; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007532:Isoleucine; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000032:analysis; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D012621:Seasons; D012720:Severity of Illness Index; D012867:Skin / Q000737:chemistry; D013912:Threonine; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D008055:Lipids; D014280:Triglycerides; D007532:Isoleucine; D013912:Threonine; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C439972:ABHD5 protein, human