Trichohepatoenteric syndrome L67.0

Trichohepatoenteric syndrome is an autosomal recessive disorder that affects the hair (tricho-), liver (hepato-), and intestine (enteric), as well as other tissues and organs in the body.

Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by a mutation in the TTC37- gene (SKIV2L gene) on chromosome 6p21 (Hartley JL et al 2010).

Trichohepatoenteric syndrome is also called syndromal diarrhea because chronic, difficult-to-treat diarrhea is one of its main features. Within the first few weeks of life, affected infants develop watery diarrhea that occurs several times a day. Trichohepatoenteric syndrome is characterized by broad phenotypic features. These include: intrauterine growth retardation, Affected individuals' hair is described as woolly, brittle, patchy, and easily plucked out(trichorrhexis nodosa - Landers MC et al 2003), facial dysmorphism (overall facial features are described as "coarse"), intractable diarrhea in infancy requiring complete parenteral nutrition, and signs of immunodeficiency.... Less commonly, trichohepatoenteric syndrome is associated with cardiac abnormalities.

Trichohepatoenteric syndrome is often life-threatening in childhood, especially in children who develop liver disease or severe infections (Hartley JL et al 2010).

Hartley et al (2010) studied 12 affected children from 11 families with THES, 8 of whom were consanguineous. All children had the characteristic facial features and trichorrhexis nodosa of the hair microscopically. There was a high incidence of preterm birth and intrauterine growth retardation. Diarrhea occurred between 2 weeks and 7 months, and all children required parenteral nutrition in infancy; in 2 patients, parenteral nutrition could be discontinued because of improvement in diarrhea. Histologic examination of serially obtained jejunal biopsy specimens revealed that villous atrophy may improve with age and that the inflammatory infiltrate is not uniform. Serum immunoglobulin levels were low in 11 of the 12 children, requiring supplementation during the neonatal period. Cardiac abnormalities were present in 5 children, including aortic regurgitation in 2, peripheral pulmonary stenosis in 1, ventricular septal defect in 1, and tetralogy of Fallot in 1. Developmental delays were present in all 7 children old enough to be studied. Previously unrecognized platelet abnormalities were noted in 6 of the children, with large platelets in 5 and thrombocytosis in 4. Transmission electron microscopy revealed reduced platelet alpha-granules, unusual stimulated release of alpha-granule contents, abnormal lipid inclusions, an abnormal platelet canalicular system, and a reduced number of microtubules.

Hartley et al (2010) performed a genome-wide linkage analysis in 8 children with trichohepatoenteric syndrome from consanguineous families and identified 3 extensive regions of homozygosity shared by all 8 children. Further genotyping in all available family members using microsatellite markers excluded 2 of the regions and confirmed linkage to chromosome 5q14.3-q21.2.

1. Barabino AV et al. (2004) Syndromic diarrhea' may have better outcome than previously reported. J. Pediat. 144: 553-554.
2. Hartley JL et al (2010) Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy). Gastroenterology 138: 2388-2398.
3. Landers MC et al (2003) Intractable diarrhea of infancy with facial dysmorphism, trichorrhexis nodosa, and cirrhosis. Pediat Derm 20: 432-435.
4. Stankler L et al (1982) Unexplained diarrhea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome. Arch Dis Child 57: 212-216.
5. Verloes A et al (1997) Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies. Am J Med Genet 68: 391-395.