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Intractable infant diarrhea associated with phenotypic abnormalities and immunodeficiency
D Girault1, O Goulet, F Le Deist
1Hematology and Immunology Unit, Inserm U 132, Paris, France.
Insights
This study describes a rare syndrome in infants characterized by severe diarrhea, distinctive physical features, and combined immunodeficiency. Early identification and management are crucial for these infants with intractable diarrhea.
Area of Science:
- Pediatric Gastroenterology
- Clinical Immunology
- Medical Genetics
Background:
- Infancy-onset intractable diarrhea presents a diagnostic challenge.
- Understanding rare genetic syndromes is key to improving patient outcomes.
Observation:
- Eight infants presented with severe diarrhea within the first six months of life.
- Common features included small for gestational age, facial dysmorphism, hypertelorism, and unique hair abnormalities (trichorrhexis nodosa).
- Patients exhibited defective antibody responses and impaired antigen-specific skin tests despite normal immunoglobulin levels.
Findings:
- Histopathology revealed villous atrophy with crypt necrosis in the jejunum and nonspecific colitis.
- Three patients had monoclonal hyper-immunoglobulinemia A.
- Poor prognosis was observed, with high mortality rates due to sepsis or cirrhosis, and significant long-term feeding challenges.
Implications:
- The described features may represent a distinct syndrome associated with intractable diarrhea of infancy.
- Further research is needed to elucidate the underlying cause and establish specific diagnostic criteria.
- This highlights the importance of recognizing complex presentations involving growth, phenotype, gastrointestinal, and immune dysfunction.
Abstract:
We report on eight children with severe diarrhea beginning in the first 6 months of life (< 1 month in six cases), who had a number of features in common. All were small for gestational age and had an abnormal phenotype, including facial dysmorphism, hypertelorism, and woolly, easily removable hair with trichorhexis nodosa. Two were products of consanguineous marriages. Severe secretory diarrhea persisted despite bowel rest (n = 7). Jejunal biopsy specimens showed total or subtotal villous atrophy with crypt necrosis, and inconstant T-cell activation in some cases (n = 3). Colon biopsy specimens showed moderate nonspecific colitis. All the patients had defective antibody responses despite normal serum immunoglobulin levels, and defective antigen-specific skin tests despite positive proliferative responses in vitro. Three had monoclonal hyper-immunoglobulinemia A. The course was marked by diffuse erythroderma in two cases and mental retardation in three. Treatment included bowel rest, intravenous administration of immune globulins, administration of corticosteroids (n = 6) and cyclosporine (n = 2), and bone marrow transplantation (n = 1). Five patients died between the ages of 2 and 5 years (of sepsis or cirrhosis), two are being fed enterally, and one continues to receive total parenteral nutrition. The cause of the combined low birth weight, dysmorphism, severe diarrhea, trichorrhexis, and immunodeficiency is unclear. These features may constitute a specific syndrome within the group of intractable diarrheas of infancy.