About ichthyosis, chanarin dorman syndrome

What is ichthyosis, chanarin dorman 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 ichthyosis, chanarin dorman 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 ichthyosis, chanarin dorman 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 ichthyosis, chanarin dorman 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 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.



What are the risk factors for ichthyosis, chanarin dorman syndrome?

Ichthyosis Chanarin Dorman syndrome (CDS) is a rare autosomal disease that is also known as Ichthyotic Neutral Lipid Storage Disease with Ichthyosis (NSLDi). The mutations in the gene ABHD5 that is located on the short arm of chromosome 3.

  • The gene encodes for a stimulating factor called the alpha-beta hydrolase domain, which is crucial for the enzyme Adipose TriGlyceride Lipase (ATGL).
  • The primary role of ATGL is to release triglycerides from lipid reserves.
  • Due to the deficiency, lipids accumulate in different parts of the body, including the liver, eyes, skin, spleen, ears, and central nervous system. The affected individuals present ichthyosis, hearing loss, hepatomegaly, cataract, splenomegaly, and mental retardation.


Risk factors

  • Familial history of the disease is a risk factor as CDS is a genetic disorder that follows the recessive pattern of inheritance.
  • Though parents are not affected by clinical manifestations, the presence of the defective gene is associated with the risk of transferring the gene to their children.
  • When both parents are carriers of the mutations, there is a 25% chance that children born to them are affected.
  • Genetic counseling is the only way to address the risk.
  • Environmental risk factors, such as alcohol abuse, obesity, and lack of physical activity, worsen the symptoms in an affected person.


Symptoms
Hyperkeratosis,Mental retardation,Muscle atrophy,Partial deafness,Liver complications,Visual impairment due to cataract
Conditions
Ichthyosis,Liver complications,Neurological deficits,Retinal dysfunction, Deafness
Drugs
Keratolytic agents like anthralin, balnetar, and salicylic acid,Oral retinoids such as acitretin, retinol, tretinoin, adapalene, tazarotene, alitretinoin, and bexarotene,Vitamin E and Urso-deoxycholic acid supplementation



Is there a cure/medications for ichthyosis, chanarin dorman syndrome?

Ichthyosis Chanarin Dorman syndrome (CDS) is a rare disorder caused by abnormally high levels of lipids in granulocytes. The accumulation primarily affects the skin, liver, heart, musculoskeletal and nervous system.

  • Normally, the body stores lipids in the cytosol of almost all types of cells.
  • Upon starvation or long fasting, enzyme constellations release the lipids in the form of triglycerides using a system of enzymes.
  • One such enzyme is Adipose Triglyceride Lipase, which is stimulated by ABHD5.
  • In patients with CDS, the lipase is deficient.


Treatment

  • Currently, there is no complete cure. However, the available treatment is only symptomatic.
  • Medium Chain Triglycerides supplementation and minimal saturated fatty acids help hepatomegaly and normalize hepatic enzymes.
  • Vitamin E and Urso-deoxycholic acid supplementation also help.
  • Topical application of emollients such as Petrolatum, dimethicone, and propylene glycol improves skin manifestations.
  • Keratolytic agents like anthralin, balnetar, and salicylic acid help with scales on the skin.
  • Oral retinoids such as acitretin, retinol, tretinoin, adapalene, tazarotene, alitretinoin, and bexarotene.
  • Factors like sunlight, irritants, friction, and heat must be avoided. These factors promote skin manifestations.
  • Avoiding activities such as alcohol consumption, and smoking, which promote the production of fatty acids within the internal organs is the best way to curb the worsening of the condition.


Symptoms
Hyperkeratosis,Mental retardation,Muscle atrophy,Partial deafness,Liver complications,Visual impairment due to cataract
Conditions
Ichthyosis,Liver complications,Neurological deficits,Retinal dysfunction, Deafness
Drugs
Keratolytic agents like anthralin, balnetar, and salicylic acid,Oral retinoids such as acitretin, retinol, tretinoin, adapalene, tazarotene, alitretinoin, and bexarotene,Vitamin E and Urso-deoxycholic acid supplementation



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