Trichohepatoenteric syndrome

Other Names: Phenotypic diarrhea; SD/THE; Syndromatic diarrhea; Syndromic diarrhea; Syndromic diarrhea/Tricho-hepato-enteric syndrome; Tricho-hepato-enteric syndrome

Trichohepatoenteric syndrome is a condition that affects the hair (tricho-), liver (hepato-), and intestines (enteric), as well as other tissues and organs in the body. This condition is also known as syndromic diarrhea because chronic, difficult-to-treat diarrhea is one of its major features. Within the first few weeks of life, affected infants develop watery diarrhea that occurs multiple times per day. Even with nutritional support through intravenous feedings (parenteral nutrition), many of these children experience failure to thrive, which means they do not gain weight or grow at the expected rate. Most children with trichohepatoenteric syndrome are small at birth, and they remain shorter than their peers throughout life.

Epidemiology

Trichohepatoenteric syndrome is a rare condition with an estimated prevalence of about 1 in 1 million people. At least 44 cases have been reported in the medical literature.

Cause

Trichohepatoenteric syndrome can be caused by mutations in the TTC37 or SKIV2L gene. These genes provide instructions for making proteins whose functions have not been confirmed. Researchers speculate that they work together with other proteins within cells to help recognize and break down excess or abnormal messenger RNA (mRNA) molecules. mRNA is a chemical cousin of DNA that serves as the genetic blueprint for protein production. Studies suggest that getting rid of excess and abnormal mRNA is important for cell growth.

Mutations in the TTC37 or SKIV2L gene likely eliminate the function of their respective proteins, which is hypothesized to impair the breakdown of unneeded mRNA. However, it is unknown how these changes could lead to chronic diarrhea and the other features of trichohepatoenteric syndrome.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

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). 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. Other symptoms associated with trichohepatoenteric syndrome include characteristic facial features such as widely spaced eyes, a broad nose, and a wide forehead. 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. Less commonly, some people with trichohepatoenteric syndrome have been born with heart abnormalities. About half of people affected by trichohepatoenteric syndrome have intellectual disability.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Immunodeficiency(Decreased immune function)
• Intractable diarrhea
• Woolly hair(Kinked hair)

30%-79% of people have these symptoms

• Brittle hair
• Broad forehead(Increased width of the forehead)
• Cirrhosis(Scar tissue replaces healthy tissue in the liver)
• Dependency on intravenous nutrition
• Global developmental delay
• Hepatic fibrosis
• Hepatomegaly(Enlarged liver)
• Hypertelorism(Wide-set eyes)
• Hypopigmentation of hair(Loss of hair color)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Panhypogammaglobulinemia
• Prominent forehead(Pronounced forehead)
• Short stature(Decreased body height)
• Small for gestational age(Birth weight less than 10th percentile)
• Trichorrhexis nodosa
• Uncombable hair
• Villous atrophy
• Wide nasal bridge(Broad nasal bridge)

5%-29% of people have these symptoms

• Abnormality of iron homeostasis
• Cafe-au-lait spot
• Colitis
• Dry skin
• Gastritis(Stomach inflammation)
• Increased mean platelet volume(Large platelets)
• Lymphopenia(Decreased blood lymphocyte number)
• Recurrent infections(Frequent infections)
• Thrombocytosis(Increased number of platelets in blood)

Diagnosis

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. 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.

Treatment

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. If the liver disease associated with trichohepatoenteric syndrome permanently damages the liver, a partial or complete liver transplant may be required.

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.

Prognosis

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. 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.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.

NIH genetic and rare disease info

• NIH info on Trichohepatoenteric syndrome

Trichohepatoenteric syndrome is a rare disease.

Trichohepatoenteric syndrome Resources
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