Dorfman-Chanarin syndrome: a case with prevalent hepatic involvement

Mela, Donatella; Artom, Alberto; Goretti, Riccardo; Varagona, G.; Riolfo, Marusca; Ardoino, Silvia Marina; Sanguineti, G; Vitali, A.; Ricciardi, Sandro

doi:10.1016/s0168-8278(96)80251-0

Cited by 19 publications

(20 citation statements)

References 9 publications

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“…This condition was originally described as neutral lipid storage disease and was more recently named Chanarin-Dorfman syndrome (CDS). Extensive clinical examination of CDS patients revealed several lipid-associated pathologies, including ichthyosis, hepatic steatosis, cardiomyopathy, ataxia, and mental retardation (15)(16)(17)(18). Several elegant studies done using fibroblasts derived from CDS patients demonstrated that the excess TG accumulation in these cells did not result from augmented fatty acid uptake or TG synthesis rates (19,20).…”

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confidence: 99%

CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells

Brown

Chung

Das

et al. 2007

Journal of Lipid Research

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Comparative Gene Identification-58 (CGI-58) is a member of the a/b-hydrolase family of proteins. Mutations in the human CGI-58 gene are associated with ChanarinDorfman syndrome, a rare autosomal recessive genetic disease in which excessive triglyceride (TG) accumulation occurs in multiple tissues. In this study, we investigated the role of CGI-58 in cellular lipid metabolism in several cell models and discovered a role for CGI-58 in promoting the packaging of cytoplasmic TG into secreted lipoprotein particles in hepatoma cells. Using both gain-of-function and loss-of-function approaches, we demonstrate that CGI-58 facilitates the depletion of cellular TG stores without altering cellular cholesterol or phospholipid accumulation. This depletion of cellular TG is attributable solely to augmented hydrolysis, whereas TG synthesis was not affected by CGI-58. Furthermore, CGI-58-mediated TG hydrolysis can be completely inhibited by the known lipase inhibitors diethylumbelliferyl phosphate and diethyl-p-nitrophenyl phosphate, but not by p-chloro-mercuribenzoate. Intriguingly, CGI-58-driven TG hydrolysis was coupled to increases in both fatty acid oxidation and secretion of TG. Collectively, this study reveals a role for CGI-58 in coupling lipolytic degradation of cytoplasmic TG to oxidation and packaging into TG-rich lipoproteins for secretion in hepatoma cells. The ability to store excess energy in the form of triglyceride (TG) is a critical defense mechanism to help organisms survive extended periods of fuel deprivation. Therefore, elegant systems have evolved to facilitate the storage of excess energy into adipose tissue in the form of TG-rich lipid droplets (LDs) or "adiposomes" (1). Although adipocytes have the unique ability to store large amounts of cytoplasmic TG, almost all tissues can synthesize and store TG in smaller cytoplasmic LDs under normal and pathologic conditions (2-4). The metabolic fate of TG in cytoplasmic LDs differs among cell types (3,(5)(6)(7)(8). Hepatocytes in the liver and enterocytes in the intestine are lipoprotein-producing cells, having the unique ability to efficiently package lipid cargo into apolipoprotein B (apoB)-containing lipoproteins that ultimately deliver these lipids to all peripheral tissues. This assembly of apoB-containing lipoproteins is widely accepted as a twostep process (7,8). The first step involves the cotranslational transfer of a small amount of phospholipids (PLs) and TGs to apoB by the actions of microsomal triglyceride transfer protein (MTP). This step results in a small dense precursor particle (?25 nm) residing within the endoplasmic reticulum (ER) lumen. The more elusive second step involves the bulk addition of TG to these precursor particles to form large (30-80 nm) secretion-competent VLDLs. This second step expansion occurs through an obscure process involving 1) the lipolysis of cytoplasmic LD-associated TG, 2) the movement of liberated acylglycerols toward the ER, and 3) the reesterification of acylglycerols to form a large lumenal TG-rich dro...

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confidence: 99%

CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells

Brown

Chung

Das

et al. 2007

Journal of Lipid Research

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“…This inherited lipid storage disease was first recognized by Dorfman in 1974 and subsequently by Chanarin in 1975 [2], coined the name in 1975. To our knowledge, since first description, 45 cases were reported to date in the world literature, most of whom have been observed in consanguineous families from the Middle East origin.…”

Section: Discussionmentioning

confidence: 99%

“…The wide spread tissue deposition of neutral lipids result in a broad spectrum of systemic manifestations. The most important feature of DCS is; congenital nonbullous ichthyosiform erythroderma and lipid vacuoles in the leucocytes (Jordan's anomaly) in the peripheral blood smear [2]. Most of cases present with skin manifestations of moderate to severe nonbullous congenital ichthyosiform erythroderma.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, 45 cases of DCS have been reported in the worldwide [4][5][6][7][8]. The majority of patients were of Middle-Eastern origin [2,9] and five of the cases were Turkish origin [6,8,10]. Herein, we report a Turkish man with the complete syndrome in addition to organ calcifications who described family history of ichthyosis.…”

Section: Introductionmentioning

confidence: 92%

“…It is characterized by ichthyosiform nonbullous erythroderma, lipid vacuoles in peripheral leukocytes and variable involvement of organs such as liver, muscle, central nervous system, eyes and ears [1][2][3]. Clinical manifestations of this syndrome related with the affected organs are; ichthyosis, myopathy, liver steatosis, sensorineural hearing loss, growth retardation, mental retardation, cataract and a variety of neurological symptoms.…”

Section: Introductionmentioning

confidence: 99%

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A case with full clinical manifestations of Dorfman-Chanarin syndrome

et al. 2007

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AbstractDorfman-Chanarin syndrome (DCS), is a rare, autosomal recessive disorder associated with lipid metabolism. It is characterized by ichthyosiform nonbullous erythroderma, lipid vacuoles in peripheral leukocytes and variable involvement of organs. We report a Turkish man with the complete syndrome, who described family history of ichthyosis. To best of our knowledge this is the sixth case from Turkish origin to date. In addition to congenital ichthyosis he had also strabismus, horizantal nystagmus, bilateral neurosensory hearing loss, hepatomegaly and splenomegaly. Liver biopsy revealed hidrophic degeneration in hepatocytes, steatosis, enlargement and inflammation in portal areas and portal central fibrosis, consistent with cirrhosis. Write stained peripheral blood smear examination revealed lipid vacuoles in all of the neutrophils consistent with Jordan’s anomaly. We think that, it is essential to evaluate the peripheral blood smear of the patients with ichthyosis and also patients with DCS should be informed and warned about the results of consanquinous marriage.

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