• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Chanarin-Dorfman Syndrome


Last updated: July 05, 2018
Years published: 1988, 1989, 1992, 1993, 1997, 2005, 2018


NORD gratefully acknowledges Maha El Barch, MD Candidate, McGill University School of Medicine, and Elena M. Pennisi, MD, PhD, Neurology Unit, Medicine Department, San Filippo Neri Hospital, Rome, Italy, for assistance in the preparation of this report.

Disease Overview


Chanarin-Dorfman syndrome (CDS) is an extremely rare genetic disorder characterized by dry, scaly skin at birth as well as progressive fatty liver disease and various degrees of muscular involvement. Vision problems, hearing loss, short stature and mild intellectual disability are also associated with this condition. The skin abnormalities are present at birth but the disease is often diagnosed a few years later in childhood when more symptoms become apparent. The current treatment options are limited, mostly for the skin symptoms. An early initiation of low fat diet with MCT (medium chain triglycerides) might improve the liver condition. Motor rehabilitation is necessary in patients with muscle disease (myopathy).


Chanarin-Dorfman syndrome was first described in 1974 in Jerusalem. Over 128 CDS patients have been reported worldwide, especially in the Mediterranean and Middle East area. CDS is a type of neutral lipid storage disease, but is also a considered a hereditary skin disease in the ‘ichthyotic’ group. It is named according to the first researchers who described patients: M.L Dorfman in 1974 and I. Chanarin in 1975.

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  • Chanarin-Dorfman disease
  • neutral lipid storage disease type I
  • CGI58 deficiency
  • disorder of cornification 12 (neutral lipid storage type)
  • DOC 12 (neutral lipid storage type)
  • Dorfman Chanarin syndrome
  • ichthyosiform erythroderma with leukocyte vacuolation
  • ichthyotic neutral lipid storage disease
  • triglyceride storage disease impaired long-chain fatty acid oxidation
  • CDS
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Signs & Symptoms

Chanarin-Dorfman syndrome can affect many systems. All patients have skin findings that are usually present at birth: redness, fine scaling, dark pigmentation and severe itching which leads to scratching and skin-picking (excoriation). The skin appearance is referred to “ichthyosiform nonbullous erythroderma”. Patients also have liver disease with lipid storage which can lead to liver failure. About 60% of patients also have muscle problems. They have slowly progressive weakness of the proximal arms and legs. When the muscles are affected they release their enzymes in the blood, which can be detected by the presence of a CK elevation. Exercise intolerance has never been reported, but many patients reported early fatigability.

Less commonly, other systems can be involved. Around 40% of patients have eye problems consisting mainly in cataracts or eyelids pointing outwards (ectropion). Approximately 25% of patients have progressive hearing loss. Around 25% have cognitive impairment. Short stature and growth retardation have also been reported. Some patients have intestinal problems such as fatty diarrhea (steatorrhea) and enlarged spleen. Some have orthopedic problems and kidney dysfunction.

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Chanarin-Dorfman syndrome is caused by changes (mutations) in the ABHD5 gene located on chromosome 3. This gene produces a protein involved in fat metabolism called CGI-58. This protein is called a co-factor because it helps the activity of the main enzyme, which is adipose triacylglycerol lipase (ATGL). The function of this enzyme is to break down a type of fat called triacylglycerol (TAG). This process is disturbed when either the enzyme or the helper protein doesn’t work properly. When the fat (triacylglycerol) cannot be broken down, it accumulates in various parts of the body as lipid droplets and causes different symptoms. This is what happens in a group of disorders called ‘neutral lipid storage disease’. It comprises two entities:

When the mutation occurs in the gene for the main enzyme (ATGL), the disease is called ‘neutral lipid storage disease with myopathy’.

When the mutation occurs in the gene for the helper protein (CGI-58), the disease is called ‘neutral lipid storage disease with itchthyosis’, or Chanarin-Dorfman syndrome.

It is important to distinguish between the two because the clinical presentations are very different. In the first one, patients usually present in early adulthood with muscle abnormalities caused by the accumulation of fat. In Chanarin-Dorfman syndrome, patients primarily have skin abnormalities that are apparent at birth. For this reason, Chanarin-Dorfman syndrome is also part of a group of diseases called ‘itchthyoses’, which are characterized by skin abnormalities. Another difference is the absence of heart problems (cardiomyopathy) in Chanarin-Dorfman syndrome, whereas they are present in first one.

The genetic mutation in Chanarin-Dorfman syndrome leads to abnormal accumulation of fat (lipid droplets) in many cells, especially in the skin, liver and white blood cells. The effect on the skin is an abnormal permeability, which leads to a characteristic rash and intense itching. In the liver, the lipid droplet accumulation leads to fatty change called “steatosis” that can eventually progress to cirrhosis and liver failure.

Chanarin-Dorfman syndrome is inherited in an autosomal recessive pattern, which means the individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the abnormal gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

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Affected populations

There have been over 128 patients reported worldwide, especially in the Mediterranean and Middle East region. Many of the reported patients have been children born to couples who are related by blood (consanguineous). This condition affects males and females equally.

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Newborns usually have characteristic skin changes (ichthyosiform changes), but the combination of skin appearance, liver abnormalities and other system involvement is what raises the suspicion for Chanarin-Dorfman syndrome. The suspected diagnosis is made with a peripheral blood smear test, where fat deposits (lipid droplets) are seen in white blood cells (called Jordan’s anomaly). Molecular genetic testing for mutations in the ABHD5 gene is available to confirm the diagnosis.

Clinical Testing and Work-Up

Most findings can be detected by a blood test: the initial diagnosis requires a peripheral blood smear, liver involvement can be detected with abnormal liver enzymes, and muscle involvement can be detected with elevated muscle enzymes and neurological clinical examination. Ultrasound of the abdomen is virtually always done to evaluate liver changes. Electromyography (EMG) can be done to evaluate the muscle changes. Biopsies of the skin, liver and muscle can be done to examine the changes under the microscope. Other systems can be examined and evaluated depending on the symptoms.

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Standard Therapies

There is no effective treatment for Chanarin-Dorfman syndrome. However, it is recommended to have a low fat diet (specifically low long-chain fatty acid and minimal saturated fat), enriched with medium-chain triglycerides, ursodiol (a bile acid) and vitamin E. This would decrease the liver size and normalize the liver enzymes. This diet has no effect on skin symptoms. To alleviate itching and other skin symptoms, it is recommended to apply moisturizers on the skin. Vitamin A derivatives like acitretin are useful for skin and muscle manifestations, but are often considered contraindicated if the liver enzymes are impaired, which is commonly the case. However, improvement in skin symptoms without deleterious effect on liver function has been reported with the use of acitretin. There is no consensus about the use of retinoid in Chanarin-Dorfman syndrome with abnormal liver function. One case of liver transplant followed by the usual dietary modifications has been reported with stabilisation of the skin and intellectual disability deterioration after 1 year, but there are insufficient studies to conclude the effectiveness and the long-term effects of liver transplantation.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Durdu M, Missaglia S, Moro L and Tavian D. Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents. BMC Medical Genetics 2018;19:88. https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0610-0

Demir B, Sen A, Bilik L,Deveci U, Ozercan H, Cicek D, Dogan Y. Charin-Dorfman syndrome. Clin Exp Dermatol. 2017;42:699-701.

Gluchowski NL, Becuwe M, Walther TC, Farese RV. Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol. 2017;14(6):343-355.

Pennisi EM, Arca M, Bertini E, et al. Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients. Orphanet J Rare Dis. 2017;12(1):90. https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0646-9

Gupta N, Gothwal S, Satpathy AK, et al. Chanarin Dorfman syndrome: a case report with novel nonsense mutation. Gene 2016;575(2 Pt 1):359-62.

Yoneda K. Inherited ichthyosis: Syndromic forms. J Dermatol. 2016;43(3):252-63.

Huigen MC, Van der graaf M, Morava E, et al. Cerebral lipid accumulation in Chanarin-Dorfman Syndrome. Mol Genet Metab. 2015;114(1):51-4.

Mogahed E, El-Hennawy A, El-Sayed R, El-Karaksy H. Chanarin-Dorfman syndrome: A case report and review of the literature. Arab J of Gastro. 2015 Sep-Dec;16(2015)142-144.

Nur BG, Gencpinar P, Yuzbasıoglu A, Emre SD, Mihci E. Chanarin-Dorfman syndrome: Genotype-Phenotype Correlation. Eur J Med Genet. 2015;58(4):238-42.

Srinivasaraghavan R, Krishnamurthy S, Chandar R, et al. Acitretin-responsive ichthyosis in Chanarin-Dorfman syndrome with a novel mutation in the ABHD5/CGI-58 gene. Pediatr Dermatol. 2014;31(5):612-4.

Aggarwal S, Maras JS, Alam S, Khanna R, Gupta SK, Ahuja A. Novel nonsense mutation of ABHD5 in Dorfman-Chanarin syndrome with unusual findings: a challenge for genotype-phenotype correlation. Eur J Med Genet. 2012;55(3):173-7.

Israeli S, Pessach Y, Sarig O, Goldberg I, Sprecher E. Beneficial effect of acitretin in Chanarin-Dorfman syndrome. Clin Exp Dermatol. 2012;37(1):31-3.

Laforêt P, Ørngreen M, Preisler N, Andersen G, Vissing J. Blocked muscle fat oxidation during exercise in neutral lipid storage disease. Arch Neurol. 2012;69(4):530-3.

Singh S, Sharma S, Agarwal S, Nangia A, Chander R, Varghese B. Neutral lipid storage disease with unusual presentation: report of three cases. Pediatr Dermatol. 2012;29(3):341-4.

Reilich P, Horvath R, Krause S, et al. The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene. J Neurol. 2011;258(11):1987-97.

Samuelov L, Fuchs-telem D, Sarig O, Sprecher E. An exceptional mutational event leading to Chanarin-Dorfman syndrome in a large consanguineous family. Br J Dermatol. 2011;164(6):1390-2.

Akman HO, Davidzon G, Tanji K, et al. Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene. Neuromuscul Disord. 2010;20(6):397-402.

Mitra S, Samanta M, Sarkar M, Chatterjee S. Dorfman-Chanarin syndrome: a rare neutral lipid storage disease. Indian J Pathol Microbiol. 2010;53(4):799-801.

Redaelli C, Coleman RA, Moro L, et al. Clinical and genetic characterization of Chanarin-Dorfman syndrome patients: first report of large deletions in the ABHD5 gene. Orphanet J Rare Dis. 2010;5:33.

Takeda K, Tanaka K, Kumamoto T, et al. Living donor liver transplantation for Dorfman-Chanarin syndrome with 1 year follow-up: case report. Transplant Proc. 2010;42(9):3858-61.

Ujihara M, Nakajima K, Yamamoto M, et al. Epidermal triglyceride levels are correlated with severity of ichthyosis in Dorfman-Chanarin syndrome. J Dermatol Sci. 2010;57(2):102-7.

Selimoglu MA, Esrefoglu M, Gul M, Gungor S, Yildirim C, Seyhan M. Chanarin-Dorfman syndrome: clinical features of a rare lipid metabolism disorder. Pediatr Dermatol. 2009;26(1):40-3.

Aksu G, Kalkan ucar S, Bulut Y, et al. Renal involvement as a rare complication of Dorfman-Chanarin syndrome: a case report. Pediatr Dermatol. 2008;25(3):326-31.


Choate K. Overview and classification of the itchthyoses. UpToDate
[https://www.uptodate.com/contents/overview-and-classification-of-the-inherited-ichthyoses?search=Chanarin%20Dorfman&source=search_result&selectedTitle=1~4&usage_type=default&display_rank=1 ] Last updated December 2016. Accessed July 3, 2018.

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