ORIGINAL ARTICLES ? Gastrointestinal abnormalities in children with autisticdisorder Karoly Horvath, MD, PhD, John C. Papadimitriou, MD, PhD, Anna Rabsztyn, Cinthia Drachenberg, MD, and J. Tyson Tildon, PhD Objectives: Our aim was to evaluate the structure and function of the upper gastrointestinal tract in a group of patients -with autism -who had gas- trointestinal symptoms. Study design: Thirty-six children (age: 5.7 ± 2 years, mean ± SD) -with autistic disorder underwent upper gastrointestinal endoscopy with biopsies, intestinal and pancreatic enzyme analyses, and bacterial and fungal cul- tures. The most frequent gastrointestinal complaints were chronic diarrhea, gaseousness, and abdominal discomfort and distension. Results: Histologic examination in these 36 children revealed grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15, and chronic duo- denitis in 14. The number of Paneth's cells in the duodenal crypts was sig- nificantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was report- ed in 21 children (58.3%), although there was no abnormality found in pan- creatic function. Seventy-five percent of the autistic children (27/36) had an increased pancreatico-biliary fluid output after intravenous secretin admin- istration. Nineteen of the 21 patients with diarrhea had significantly higher fluid output than those without diarrhea. Conclusions: Unrecognized gastrointestinal disorders, especially reflux esophagitis and disaccharide malabsorption, may contribute to the behav- ioral problems of the non-verbal autistic patients. The observed increase in pancreatico-biliary secretion after secretin infusion suggests an upregula- tion of secretin receptors in the pancreas and liver. Further studies are re- quired to determine the possible association between the brain and gastroin- testinal dysfunctions in children with autistic disorder. (J Pediatr 1999; 135:559-63) . ; \ From the Departments of Pediatrics and Pathology, University of Maryland School of Medicine, Baltimore. Supported by an intramural grant by the University of Maryland School of Medicine. Submitted for publication Dec 31, 1998; revision received May 20, 1999; accepted July 21, 1999. Reprint requests: Karoly Horvath, MD, PhD, Department of Pediatrics, 22 S Greene St, N5W70, Box 140, Baltimore, MD 21201-1595. Copyright © 1999 by Mosby, Inc. 0022-3476/99/S8.00 +0 9/21/101636 Autistic disorder belongs to the group of pervasive developmental disorders as defined by both the American (Diag- nostic and Statistical Manual of Mental Disorder*}, Fourth Edition) and interna- tional (International Classification of Dis- eases, Ninth Revision) diagnostic systems. Autistic disorder implies severity of dis- turbance in multiple areas of develop- ment reflected in a marked lack of de- velopment of social interaction and communication; restricted, repetitive, and stereotyped patterns; and typical prelinguistic communicative behaviors. In addition to the abnormalities in com- munication and language skills, these children frequently have aggressive and self-injurious behaviors. Sudden unexplained irritability or aggressive behavior, nighttime awakening, and pushing on the abdomen are usually considered part of the behavioral prob- lems associated -with autism. See editorial, p. 533. Many parents report gastrointestinal symptoms in their autistic child; how- ever, until recently, gastrointestinal symptoms of these children received little attention. In 1996, D'Eufemia et al reported increased intestinal per- meability in 9 of 21 (43%) patients with autistic disorder. The report of Wakefield et al represents the first ef- fort to evaluate the gastrointestinal tract in children with autism. In a re- cent case report we described 3 chil- 559