Syndromic (phenotypic) diarrhea in early infancy

Olivier Goulet¹ , Christine Vinson² , Bertrand Roquelaure³ , Nicole Brousse⁴ , Christine Bodemer⁵ and Jean-Pierre Cézard²

¹Pediatric Gastroenterology-Hepatology and Nutrition, Reference Center for Rare Digestive Disease, Hôpital Necker-Enfants Malades/AP-HP, University of Paris 5 – René Descartes, France

²Pediatric Gastroenterology and Nutrition, Reference Center for Rare Digestive Disease, Hôpital Robert Debré/AP-HP, University of Paris 7, France

³Pediatric Gastroenterology and Nutrition, Hôpital de la Timone, University of Marseille, France

⁴Department of Pathology, Hôpital Necker-Enfants Malades/AP-HP, University of Paris 5 – René Descartes, France

⁵Pediatric Dermatology, Reference Center for Rare Dermatologic Disease, Hôpital Necker-Enfants Malades/AP-HP, University of Paris 5 – René Descartes, France

author email corresponding author email

Orphanet Journal of Rare Diseases 2008, 3:6doi:10.1186/1750-1172-3-6


Published:	28 February 2008

Abstract

Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases) and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature.

Disease name and synonyms

Syndromic diarrhea – Phenotypic diarrhea – Tricho-hepato-enteric syndrome – Intractable diarrhea of infancy with facial dysmorphism – Trichorrhexis nodosa and cirrhosis – Neonatal hemochromatosis phenotype with intractable diarrhea and hair abnormalities – Intractable infant diarrhea associated with phenotypic abnormalities and immune deficiency.