About dorfman chanarin syndrome

What is dorfman chanarin syndrome?

Chanarin Dorfman syndrome is a rare hereditary disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy), and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids).

What are the symptoms for dorfman chanarin syndrome?

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.

What are the causes for dorfman chanarin syndrome?

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.

What are the treatments for dorfman chanarin syndrome?

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 to 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 retinoids in Chanarin-Dorfman syndrome with abnormal liver function. One case of liver transplant followed by the usual dietary modifications has been reported with stabilization 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.

What are the risk factors for dorfman chanarin syndrome?

The exceedingly rare genetic ailment Chanarin-Dorfman syndrome (CDS) is characterized by dry, scaly skin at birth, increasing fatty liver disease, and varying degrees of muscle involvement. This syndrome is also accompanied by hearing loss, small stature, vision issues, and slight intellectual handicap.

  • The disease is frequently discovered a few years later in childhood when more symptoms start to appear, even though the skin abnormalities are present at birth. There are few therapeutic options available right now, primarily for skin issues.
  • Because Chanarin-Dorfman syndrome is inherited via an autosomal recessive pattern it would be risky, each parent contributes a defective gene to the affected person.
  • A person will be a carrier of the disease if they have one normal gene and one faulty gene for it, although they often won't exhibit any symptoms.
  • With each pregnancy, there is a 25% chance that two carriers may convey the defective gene to their unborn kid and result in a child that is affected.
  • With every pregnancy, there is a 50% chance that the unborn kid will also be a carrier, like the parents. A child has a 25% chance of inheriting normal genes from both parents. Both men and women are at the same level of danger.


Symptoms
Redness,Fine scaling,Pigmentation and itching leading to scratching,Skin-picking (excoriation),Slowly progressive weakness of the proximal arms and legs
Conditions
Ectropion,Steatorrhea,Ichthyosiform nonbullous erythroderma
Drugs
Triglycerides,Ursodiol (a bile acid),Vitamin E supplements

Is there a cure/medications for dorfman chanarin syndrome?

The exceedingly rare genetic ailment Chanarin-Dorfman syndrome (CDS) is characterized by dry, scaly skin at birth, increasing fatty liver disease, and varying degrees of muscle involvement. This syndrome is also accompanied by hearing loss, small stature, vision issues, and slight intellectual handicap.

  • Chanarin-Dorfman syndrome (CDS) recessively inherited condition also known as Neutral Lipid Storage Disease with Ichthyosis (NLSDI). Both men and women are equally impacted.
  • The clinical description that follows is based on the outcomes of roughly 50 instances with ABHD5 mutations that have been validated. The Middle East and Japan have seen the majority of reported cases.
  • Chanarin-Dorfman has no proven cure. However, a low-fat diet that is loaded with medium-chain triglycerides, ursodiol (a bile acid), and vitamin E are advised, with a focus on low long-chain fatty acids and minimal saturated fat. This would reduce the size of the liver and restore normal levels of liver enzymes. Skin complaints are unaffected by this diet.
  • Applying moisturizers to the skin is advised to reduce itching and other skin issues. Acitretin, a vitamin A derivative, is helpful for skin and muscle symptoms but is frequently prohibited if the liver enzymes are compromised, which is frequently the case.
  • However, the administration of acitretin has been observed to relieve skin complaints without having a negative impact on liver function.


Symptoms
Redness,Fine scaling,Pigmentation and itching leading to scratching,Skin-picking (excoriation),Slowly progressive weakness of the proximal arms and legs
Conditions
Ectropion,Steatorrhea,Ichthyosiform nonbullous erythroderma
Drugs
Triglycerides,Ursodiol (a bile acid),Vitamin E supplements

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