Trichohepatoenteric syndrome

Trichohepatoenteric syndrome is named after the three main body systems that it affects: hair (tricho), liver (hepato), and intestines (enteric). The hair of people who have trichohepatoenteric syndrome may be wooly, patchy, or brittle. The hair may easily fall out due to each strand of hair having many thickened points surrounded by weak points (trichorrhexis nodosa).^[3] Trichohepatoenteric syndrome is also characterized by liver disease such as cirrhosis (chronic liver damage) or hepatomegaly (swollen liver). The intestinal problems associated with the condition are most characteristic of the disease. These problems include chronic diarrhea beginning in the first 6 months of life.^[2]

Other symptoms associated with trichohepatoenteric syndrome include characteristic facial features such as widely spaced eyes, a broad nose, and a wide forehead.^[3] People with trichohepatoenteric syndrome may also have a weakened immune system that makes it more difficult to fight infection. Some people may have skin abnormalities such as lightly-colored spots (café-au-lait macules), dry skin (xerosis), or skin that has a rubbery texture.^[2] Less commonly, some people with trichohepatoenteric syndrome have been born with heart abnormalities. About half of people affected by trichohepatoenteric syndrome have intellectual disability. 

Trichohepatoenteric syndrome is caused by mutations (changes) in one of two genes: TTC37or SKIV2L. These genes are known to provide instructions to the body to help get rid of excess mRNA. mRNA allows the body to turn the molecular genetic code (DNA) into proteins that have specific functions in the body. It is not known exactly how mutations in TTC37 or SKIV2L cause the symptoms of trichohepatoenteric syndrome.^[3] 

Trichohepatoenteric syndrome is inherited in an autosomal recessive manner.^[3] This means that mutations in both copies of either gene are required for a person to have symptoms of trichohepatoenteric syndrome. People who only have one copy of a gene that is changed are known as carriers. Carriers do not have symptoms of trichohepatoenteric syndrome. Each child of two carriers has a:

• 25% chance of having trichohepatoenteric syndrome
• 50% chance of being a carrier like both parents
• 25% chance of being unaffected and not being a carrier

Trichohepatoenteric syndrome is diagnosed after an examination by a doctor shows symptoms suggestive of the condition. The exam might include a physical examination as well as a biopsy of the small intestine to search for other causes of the chronic diarrhea. A small intestine biopsy of people who have trichohepatoenteric syndrome may show some degeneration (atrophy) of the villi of the small intestine.^[2]

After a clinical examination is found to be suggestive of trichohepatoenteric syndrome, a doctor may order genetic testing to confirm the diagnosis. Genetic testing would look for mutations in both copies of TTC37 or SKIV2L. 

Trichohepatoenteric syndrome is treated symptomatically, meaning it is focused on treating the symptoms of the disease. Treating the chronic diarrhea is often the biggest concern, as chronic diarrhea can prevent people with trichohepatoenteric syndrome from getting enough nutrients. In most cases, treatment requires nutrition through an intravenous line, or IV. This is also called parenteral nutrition.^[1] If the liver disease associated with trichohepatoenteric syndrome permanently damages the liver, a partial or complete liver transplant may be required.^[2]

It may also be necessary to treat the weakened immune system associated with trichohepatoenteric syndrome. People with the condition may need treatment such as immunoglobulin infusions to boost the immune system.^[4]

Unfortunately, liver disease or a weakened immune system resulting in severe infections cause about 50% of people affected by trichohepatoenteric syndrome to pass away during childhood.^[2] However, individuals that survive childhood may no longer require IV nutrition. Most people with trichohepatoenteric syndrome will be smaller than other people their age. The mild intellectual disability associated with trichohepatoenteric syndrome may require a person to have special classes in school.

In some rare cases, people with trichohepatoenteric syndrome are found to have only mild diarrhea.^[4] This may mean that our current understanding of trichohepatoenteric syndrome is only based on a small group of people who have the condition. It is possible that there are more people who have the condition but only have mild symptoms.