You are on page 1of 14

Childhood Malabsorption

Michelle M. Pietzak and Dan W. Thomas
Pediatrics in Review 2003;24;195
DOI: 10.1542/pir.24-6-195

The online version of this article, along with updated information and services, is
located on the World Wide Web at:

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2003 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601.

Downloaded from at Pakistan:AAP Sponsored on November 20, 2013

short stature. Crohn disease cystic fibrosis immunoglobulin protein-losing enteropathy fecal alpha-1-antitrypsin excretion test Epidemiology and Pathophysiology Nutrient absorption is an efficient process that is regionalized in the gut and depends on pancreatic and hepatobiliary secretory function. University of Southern at Pakistan:AAP Sponsored on November 20. and occasional diarrhea in a teen who has Crohn disease (CD). Nevertheless. detailed dietary intake. 2. Nutrition Support Team. Conversely. Describe the procedure for distinguishing pancreatic or other intraluminal causes of malabsorption from intestinal mucosal absorptive defects. Introduction Abbreviations CD: CF: Ig: PLE: FA1AT: The dilemma of determining whether a child has malabsorption is common in clinical practice.aappublications. Pietzak. many children who have malabsorptive disorders have loose stools only occasionally or no diarrhea. Childrens Hospital Los Angeles.Article gastroenterology Childhood Malabsorption Michelle M. failure to thrive.6 June 2003 195 Downloaded from http://pedsinreview. Explain why congenital mucosal malabsorptive defects almost always present in early infancy with massive diarrhea and dehydration. MD† Objectives After completing the article. there is a frequent misconception that children who have malabsorption experience chronic diarrhea. Many of these otherwise healthy children drink excessive amounts of sweetened beverages and are labeled as having toddler’s diarrhea. weight loss. 3. Overall gastrointestinal function depends on development but is relatively efficient at birth. chronic diarrhea.24 No. rickets. CA. Other clinical details are useful in the evaluation for malabsorption. evolving anemia. or a loss of developmental milestones and organomegaly in a child who has a lipid storage disorder. † Associate Professor of Pediatrics and Head. Name the extraintestinal signs or symptoms that many children who have underlying chronic digestive disorders might have without specific digestive complaints. Neonates and young infants have a reduced ability to digest fat because *Assistant Professor of Clinical Pediatrics and Medical Director. and subnormal growth. There may be other signs of severe malnutrition. the clinician initially should attempt to determine whether failure to thrive is related to a deficient diet. such as edema. The physical examination also may reveal other phenotypic findings consistent with congenital disorders associated with suboptimal growth and nutrition (eg. A thorough history. Los Angeles.” Gastrointestinal dysfunction is linked inexorably as a possible cause of failure to thrive. or abnormal energy utilization. Important signs include malodorous stools. systolic hypertension. such as a goiter. Pediatrics in Review Vol. Follow-up assessment may reveal dietary discrepancies or clinical findings. assessment of the family environment. For example.* Dan W. and complete physical examination usually suggest one of these three causes. decreased muscle mass. or a “potbelly. However. children who have watery stools may not have significant gastrointestinal dysfunction. Russell Silver syndrome). Gastroenterology. Thomas. Keck School of Medicine. The child’s height. malabsorption. readers should be able to: 1. Delineate the specific signs with which generalized malabsorption frequently is associated. and tremor suggestive of a thyroid disorder. and head circumference (for infants) should be plotted serially on a growth chart. MD. These children often drink excessive amounts of juices in child care facilities or at a baby-sitter’s. 2013 . excessive bleeding or bruising. weight. 4.

The fate of each of the major nutrients. and venous and lymphatic transport phases.or medium-chain fatty acids are digested and absorbed by a similar process. The osmotic properties of malabsorbed carbohydrate lead to excessive accumulation of intraluminal fluid and diar- rhea. is characterized separately in terms of these digestive phases. a screening test for PLE. and water. is useful in distinguishing intraluminal from mucosal maladies. vitamin B12 and bile acids are absorbed selectively in the terminal ileum. Dietary fats are emulsified intraluminally within small digestive packets called micelles. Numerous causes of PLE generally are attributable to intestinal damage or impediment of mesenteric lymphatic or venous flow. short bowel syndrome. As mentioned. A noninvasive test quantifies the amount of hydrogen that is produced by gut fermentation in exhaled air (hydrogen breath test). 196 Pediatrics in Review Vol. and gases. Although the exact mechanisms for PLE are not known.24 No. Carbohydrate malabsorption may be due to excessive intake. which facilitate mixing with pancreatic enzymes. such as CD. The mucosal phase of digestion typically is defective in cases of carbohydrate malabsorption. Protein Nature seems to preserve and retain the ability to digest protein despite most adversities. Conditions that result in generalized malabsorption of other nutrients rarely cause profound azotorrhea. In addition. it generally occurs because of excessive weeping of serum protein into the bowel beyond what subsequently can be digested and reabsorbed downstream in the gut. Hence. fats. Children who have intraluminal malabsorptive defects. including carbohydrates. The digestive and absorptive process usually is categorized into intraluminal. The significant malabsorption that occurs in patients who have CF can result in azotorrhea. However. organic acids (eg. such as the fecal alpha1-antitrypsin excretion test (FA1AT). but are transported directly to the liver via mesenteric venous blood flow. This is especially true for children who have disorders of the terminal small bowel. or congenital intestinal transport or enzyme deficiencies. Carbohydrates Watery. This difference in the absorptive process allows enhancement of energy absorption of dietary fat by supplementation with mediumchain triglycerides. which is capable of causing colitis and diarrhea. loose stools usually occur because of malabsorbed carbohydrate or other osmotically active substances. mucosal. Short. ileocolonic bacteria ferment malabsorbed dietary sugars and carbohydrates into simple sugars. any cause of mucosal damage. do not have PLE because their digestive defect does not involve mucosal damage. Examples of disorders that result in a defective intraluminal phase of digestion are pancreatic insufficiency due to cystic fibrosis (CF) and hepatobiliary dysfunction associated with biliary atresia.gastroenterology childhood malabsorption of developmental delay in pancreatic and hepatobiliary function. proteins. but rather is due to a combination of deficient dietary intake and excessive intestinal protein loss termed protein-losing enteropathy (PLE). An elevated FA1AT result suggests a disorder such as celiac disease or CD rather than CF or liver disease. Hence. the colon is an important adjunctive digestive organ in children who have small bowel digestive dysfunction or short bowel syndrome. minerals. Malabsorbed bile acids are deleterious to the colonic mucosa because of their detergent action. Examples include the competitive absorption of zinc and copper and the cotransporter for sodium and glucose. Chylomicrons are transported via lymphatics to the venous circulation and eventually to the liver for metabolism and repackaging. vitamins. However. Development of coordinated intestinal peristalsis is important in facilitating digestion. 2013 .6 June 2003 Downloaded from http://pedsinreview. This occurs normally in breastfed infants. Cotransport of Nutrients Codependency of nutrient absorption is common. Consequently. as in CF. and hydrogen are common gaseous by-products. but even more so in children who have short bowel syndrome. Methane. Fats Pancreatic and hepatobiliary secretions mix with nutrients in the duodenum and proximal jejunum to result in the digestion of dietary fat. The hypoproteinemia that occurs in some children who are undernourished and have generalized malabsorption usually is not because of at Pakistan:AAP Sponsored on November 20. Most nutrient digestion and absorption occurs in the proximal small intestine. healthy infants may have visible fat in their stools.aappublications. There is bulk flow of water through the porous junctions of the proximal small intestinal epithelial cells. the colon can serve as a “stopgap” digestive organ. carbon dioxide. These fermentative by-products can be used to detect carbohydrate malabsorption. Peristaltic abnormalities are common in preterm infants and very ill children. Intraluminal dietary fat digestion produces long-chain fatty acids that are absorbed and repackaged into chylomicrons by epithelial cells. electrolytes. malabsorption of carbohydrates results in excessive fermentation by bacteria in the distal ileum and colon. short-chain fatty acids).

24 No. Stasis allows bacterial overgrowth that can deplete the body of vitamin B12 and other minerals and nutrients as well as causing steatorrhea. It has been conjectured that certain CF DNA mutations.gastroenterology childhood malabsorption Pharmacologic amounts of zinc can impede copper absorption from the gut in patients who have excessive tissue accumulation of copper due to Wilson disease. The primary pathophysiologic abnormality in CF is defective chloride channel function that results in generalized dysregulation of salt and water flux across epithelial glandular cells. Rare motility disorders are a cause of this syndrome. Although most patients who have lung disease and pancreatic insufficiency have the Delta F508 mutation. The electrolyte content of stool disease. Disease results from inspissated plugging by proteinaceous secretions in affected organs. but most patients have a history of congenital gut anomalies or prior gastrointestinal surgery. The hallmark of secretory diarrhea is voluminous. congestion. the phases of digestion remain generally intact. Oral fluids that contain excessive salt or sugar are ineffective and are likely to cause osmotic diarrhea and free water loss. Glucose. Elucidation of the intestinal sodium-glucose cotransporter was instrumental in advancing knowledge of the physiology of salt and water absorption. Affected patients frequently have macrocytic anemia. Approximately 1 in 25 Caucasians carries at least one CF DNA mutation. severe gastrointestinal mucosal injury. For example. Hypokalemia occurs frequently in association with secretory neoplasms. Long-term complications include at Pakistan:AAP Sponsored on November 20. This remains to be substantiated. bloating. secretory tumors (eg. and diabetes. vitamin K and folate are produced and made available for absorption from nutrients in the diet by intestinal bacterial metabolism. There is multiorgan involvement.aappublications. The stools are bulky or sometimes loose. Intestinal bacteria generally are commensal. CF is caused by mutations in the CFTR gene. The most common mutation is Delta F508. Secretory Diarrhea This condition not only results in fluid and electrolyte losses. CF is rare but does occur in noncaucasians. those who have celiac disease have an elevated fecal alpha 1-antitrypsin excretion test. The most common presentation of CF is an infant who has persistent cough. These organisms help ferment undigested nutrients and maintain distal bowel integrity. Cholera is the prototype infection capable of producing a toxin that causes severe secretory diarrhea. these individuals are asymptomatic.000 to 4. Some Pediatrics in Review Vol. but in malabsorption if prolonged and severe. or Zollinger-Ellison syndrome). may predispose to chronic liver or pancreatic Children who have cystic fibrosis do not have protein-losing enteropathy. and failure to thrive. The sodium-glucose cotransporter is well preserved during gastrointestinal infections. and diarrhea. carcinoid syndrome. but the gut is overcome by the massive efflux of fluid and salt. The reported incidence of CF in Caucasians in the United States ranges from 1 in 2. Secretory diarrhea is encountered more often in children who have short bowel syndrome. and the “good” bacteria in the distal small intestine and colon are beneficial. Bacterial Overgrowth Syndrome Disorders of intestinal peristalsis and other causes of gut stasis often result in malabsorption.6 June 2003 197 Downloaded from http://pedsinreview. Many mutations are undetected by genetic screening. with characteristic disease of lung and pancreas and variable disease in the gastrointestinal tract. even when heterozygotic. watery stools despite bowel rest. hepatobiliary system. obstipation (distal intestinal obstruction syndrome). or as a result of a toxin produced from a gastrointestinal pathogen. but hundreds of other mutations have been identified. salt. 2013 . effluent approaches that of serum. which is located on chromosome 7 at position 7q31.000 live births. further research is needed to determine associations between specific CFTR mutations and phenotypic disease expression. Causes of Malabsorptive Syndromes Pancreatic Disorders CF is one of the most common serious malabsorptive disorders. and the reproductive tract. and water absorption can be maintained by feeding a child who has acute viral gastroenteritis a balanced glucose and electrolyte solution that contains optimal molar ratios of salt and glucose. In these clinical situations. This spurred development of present day oral rehydration solutions for acute diarrheal dehydration. neuroblastoma.

glycogen storage disease. decreased or absent deep tendon reflexes. its incidence in CF is about 20%. Chronic Cholestasis As discussed previously.000 live births. These procedures are difficult to perform and usually are unnecessary. We recently cared for a 3-year-old AfricanAmerican and a teenage Caucasian who had rectal prolapse as their primary clinical problem and subsequently were found to have CF. this testing may miss some cases. The test performed most easily for pancreatic insufficiency in a young infant is the semiquantitative test for trypsin in the stool. This test is not useful for older children and adults. 2013 . Sweat test results may be false-positive in adrenal insufficiency. There may be a family history or other syndromic features. The phenotypic features include short stature. Aside from signs of malabsorption. unexplained chronic liver disease or chronic pancreatitis. peculiar whorls of tissue in their scalps. and skeletal and rib abnormalities. including pancytopenia and cyclic neutropenia. and the most frequent cause. Infants who have meconium ileus present soon after birth with signs of bowel obstruction that can be alleviated by acetylcysteine rectal irrigations or operative purging of the bowel at an experienced center. and hypothyroidism. and other very rare conditions. Alagille syndrome is one of the more common syndromic cholestatic disorders.24 No. but as mentioned. Other presumptive diagnostic tests include assessing for the presence of inspissated proteinaceous material in tissue biopsies. and diabetes may occur. malnutrition. nephrogenic diabetes insipidus.6 June 2003 Downloaded from http://pedsinreview. Meconium ileus is a consequence of the tenacious meconium that accumulates in the terminal ileum and proximal colon in utero. absent nasal cartilage. chronic malnutrition. The pancreatic insufficiency is due to fatty replacement. and hemolytic anemia. There also are rare conditions that are either syndromic or related to specific inherited bile duct epithelial transport defects. infections and infestations causing proctocolitis. Vitamin E deficiency is of special concern because several interrelated digestive steps are necessary for absorption of this vitamin. Patients often have abnormal vitamin K malabsorption and reduced hepatic synthesis of coagulation factors.aappublications.gastroenterology childhood malabsorption affected neonates have cholestasis or meconium ileus. less frequent causes of pancreatic insufficiency. Similarly. meconium ileus. 198 Pediatrics in Review Vol. Signs of vitamin E deficiency include ataxia. children who have recurrent lung problems may not have any other signs of this disorder and are diagnosed later in life. recurrent infections. We have cared for school-age children who have CF and present initially with acute pancreatitis. ectodermal at Pakistan:AAP Sponsored on November 20. sinusitis. inherited cholestasis. any hepatobiliary disorder that results in chronic cholestasis can cause steatorrhea. severe functional constipation. and various forms of bone marrow dysfunction. Consequently. Patients characteristically have gastrointestinal anomalies (imperforate anus). phenotypic facial features. children who have any chronic lung condition. anorexia nervosa. skeletal abnormalities. intussusception. and tests for pancreatic insufficiency. also included are rectal polyp. Chronic cholestasis is evident to the practitioner because of the child’s enlarged liver and jaundice. Although CF is part of the differential diagnosis of rectal prolapse. The bowel can be twisted and become atretic in utero. CF DNA mutation tests can be obtained. unexplained digital clubbing. children who have chronic cholestasis often experience growth failure. Very young infants who have CF can have generalized edema without other symptoms. The Johanson-Blizzard syndrome occurs less frequently than Shwachman syndrome but is another recognized cause of childhood pancreatic insufficiency and malabsorption. transnasal conductance measurements. Two syndromic conditions are among the other. bone marrow. Most children who have persistent cholestasis from early infancy have biliary atresia. hypoparathyroidism. Affected children also have congential heart disease (usually peripheral pulmonic stenosis). nasal polyps. ocular palsy. CF usually is diagnosed by performing a sweat chloride test. False-negative results can occur with malnutrition and generalized edema and in very young infants who have CF. The pancreatic. deafness. and fatsoluble vitamin deficiencies. short stature. hyperthyroidism. The exact cause of this autosomal recessive disorder is not yet known. and skeletal abnormalities are due to hypoplasia and other embryologic mesenchymal abnormalities. rectal prolapse. Shwachman syndrome is estimated to occur in 1 in 10. or unexplained failure to thrive and infants who have hypoproteinemia and edema should be screened for CF. Pancreatic enzyme levels also can be measured by direct endoscopic sampling of ductal secretions from the ampulla of Vater. Many children who have CF do not present in early infancy and have clinical signs related to primary organ involvement later in life. severe malnutrition. Children who have chronic cholestasis or any form of chronic malabsorption should be screened for fat-soluble vitamin deficiencies.

Normal intestinal mucosal biopsy. and some are constipated. Gastrointestinal Mucosal Surface Injury: Celiac Disease Clinicians have been aware of the existence of celiac disease for centuries. Immunohistochemical stains of biopsies can be performed to enhance diagnostic accuracy (Fig.” wasted extremities. but this no longer is recommended unless the diagnosis is uncertain. Behavioral changes and emotional lability are common. The current gold standard for diagnosis of celiac disease is a small intestinal biopsy to confirm the presence of mucosal damage while the patient is on a glutencontaining diet (Figs. some children have musculoskeletal abnormalities. delayed puberty. We also have encountered a few patients who had initial autoimmune liver disease and later were found to have celiac disease. rheumatoid arthritis. and central nervous system calcifications.24 No. irritability. The classic case is the infant who has a “potbelly. asymptomatic forms. with the enteritis appearing to be most severe proximally. and delayed-onset disease. or celiac sprue. family history. depression. The overall incidence worldwide is uncertain. schizophrenia. 3). More than 99% of affected people are positive for human leukocyte antigen-DQ2 or -DQ8. bulky stools. and a similar estimated incidence in the United States.6 June 2003 199 Downloaded from http://pedsinreview. although oats in the United States usually are milled with other grains that contaminate the mixture with gluten and may cause problems. Celiac disease. In the past. a link has been shown between celiac disease and epilepsy. The disorder appears in genetically susceptible individuals who sustain an autoimmune reaction to the toxic gliadin protein fraction of gluten. It is not uncommon for affected patients to have a complex anemia from iron. with a frequency of 1 in 100 to 500. 1 and 2). Infertility and a history of spontaneous abortions are encountered in undiagnosed women. The disease results from progressive inflammatory damage to small bowel mucosa. sometimes called gluten-sensitive enteropathy. Research at our center suggests an incidence of celiac disease of 1 in 12 patients who have type 1 diabetes. The clinical presentation of celiac disease can vary. Patients who have celiac disease have laboratory evidence of generalized malabsorption and anemia. Curiously. and barley. folate. and the results of antibody screening tests. and dental defects. There is a strong association between celiac disease and other autoimmune disorders. and other vasculitic disorders. rye. Because extraintestinal disease and malabsorption occur. Celiac disease also is more common in autoimmune thyroid disorders. sprue. 2013 . Patients also may have recurrent aphthoid oral lesions. Rice and corn are not offending agents. Sinatra. It is very common in Northern European and Scandinavian countries. There is a strong trend for inheritance with certain identified susceptibility risk factors. In Pediatrics in Review Vol. short stature. nontropical sprue. with extraintestinal manifestations predominating. Pure oats probably should not be considered an offending agent. Patients should undergo intestinal biopsy based on symptoms. Gluten protein is derived from a group of cereal grains that include wheat. Extraintestinal problems are common. Symptoms range from severe diarrhea and malnutrition to a paucity of clinical complaints. but is believed to be far greater than previous estimates of 1 in 4. Photo courtesy of Dr Frank R. and marked crypt hyperplasia. and laboratory evidence of malabsorption. There are more subtle at Pakistan:AAP Sponsored on November 20. or vitamin B12 deficiencies. is becoming the prototypic model for autoimmune disease. Severe celiac disease with total villous atrophy of the duodenal mucosa. lymphocytic infiltrate.aappublications. based on recent prospective studies. biopsies were recommended when the patient was both on and off gluten to document a histologic response.gastroenterology childhood malabsorption Figure 1. These youngsters do not necessarily have diarrhea. serial Figure 2.000.

A positive antigliadin IgG antibody test only in conjunction with a normal serum IgA level is not considered to be of significance unless seen in a child younger than 2 years of age or if the antigliadin antibody level is three to four times above normal. Malabsorption can range from lactose intolerance in some patients because of generalized small bowel mucosa injury to severe generalized nutrient malabsorption due to full-thickness bowel injury with dysmotility and bleeding. Affected patients may have serum IgA deficiency. and antitissue transglutaminase IgA antibodies.aappublications. This technique helps to detect cases of celiac disease when typical histologic features of villous atrophy are absent. but usually this is a clinical problem in debilitated or immunodeficient children.gastroenterology childhood malabsorption of a lifelong gluten-free diet. and stool test for occult blood (positive). Patients experience intermittent symptoms of at Pakistan:AAP Sponsored on November 20. Patients who have CD also may experience malabsorption due to rapid intestinal transit. antiendomysial IgA. These include infertility. severe cases. delayed puberty. In a retrospective study of patients at our center. The profound digestive effects of this illness ultimately can result in growth failure. PLE is common in CD. there is malabsorption of fat-soluble vitamins and hypoproteinemia. and bulky stools. diarrhea. Infectious Diarrhea: Giardiasis Chronic giardiasis often masquerades as other digestive disorders. 2013 . but they are still at increased risk for gastrointestinal cancers and extraintestinal medical problems. psychological and neurologic problems. Suggestive positive screening results include the presence of more than one positive antibody test without IgA deficiency. especially in the presence of clinical symptoms or a family history. Other useful screening tests include a complete blood count (high white blood cell count or anemia). the clinical presentation of CD is varied and sometimes very subtle. multiple different clinical pictures are possible. The anemia associated with CD can be multifactorial. Fecal alpha-1-antitrypsin excretion is abnormal because of PLE. and vitamin B12 deficiencies.24 No. A positive IgG antigliadin antibody test and IgA deficiency also are suggestive. and vitamin and trace element deficiencies. Stain for CD3-positive intraepithelial lymphocytes in a diabetic child who had chronic intermittent diarrhea and positive celiac antibody screening tests. Some patients feel that partial compliance is adequate to control their symptoms. screening blood tests consist of antigliadin immunoglobulin G (IgG) and IgA. and osteoporosis. Newer screening blood tests include perinuclear anticytoplasmic antibody (usually positive in ulcerative colitis) and antisaccharomyces cerevisiae antibody (frequently positive in CD). The latter is common in CD because of the predilection for the terminal ileum. Giardia trophozoites can infest healthy children chronically. erythrocyte sedimentation rate (high). Treatment of celiac disease hinges on implementation Just as for celiac disease. Crohn Disease Figure 3.and micronutrient deficiencies in children who have subtle signs of CD. Youngsters who have selective IgA deficiency are particularly susceptible to persistent giardiasis. we usually obtain a serum IgA level. The latter finding is nonspecific and suggests increased gut permeability and possible underlying bowel disorder. For this reason. they also may have subnormal growth and other signs of 200 Pediatrics in Review Vol.6 June 2003 Downloaded from http://pedsinreview. more than 90% of patients had evidence of PLE. Presently. encompassing iron. Intestinal strictures can cause bacterial overgrowth syndrome. folate. we found the FA1AT to be the most common initial abnormal laboratory test. Because CD may affect any part of the digestive system or body. A high index of suspicion as well as the availability of blood screening tests for inflammatory bowel disease should prevent longstanding macro.

The response to treatment is variable and inconsistent. and have other serious medical illnesses are susceptible to secondary lactose malabsorption. although severe outbreaks have been reported in young healthy children.6 June 2003 201 Downloaded from http://pedsinreview. Diagnosis is made by selective examination of the stool for Cryptosporidium or identification of the organism in the effluent or mucosal biopsies from the proximal small bowel. children who have preexisting digestive disorders. The diagnosis is made by finding the organism on proximal intestinal biopsy (Fig.24 No. Clinicians should have a high index of suspicion for giardiasis in children who have persistent diarrhea if the child attends child care. The diarrhea often is classified as osmotic because of malabsorption of dietary sugars and carbohydrates. or a commercial solution. and watery diarrhea. The diarrhea is usually watery and nonbloody. specialized diets or lactose-free formulas are necessary. In these cases. lives near or visits lakes or streams. or has lived in or visited underdeveloped regions. most previously healthy children who have acute diarrheal illnesses with or without dehydration are not likely to have sustained gastrointestinal dysfunction. Realimentation is a slow. infants who are breastfed do relatively well with continuation of breastfeeding in addition to supplemental oral rehydration solution ad libiPediatrics in Review Vol. Children who have profound intestinal damage. patients who have acquired and congenital immune deficiencies are susceptible to a prolonged and debilitating diarrheal illness that is characterized by malabsorption of fluid. As with giardiasis. The latter is a reliable and widely available clinical test. This stems from mucosal damage that results in loss of the lactase enzyme on the intestinal brush border. can have deficiencies of most brush border enzymes. Secondary acquired milk and soy formula allergies make management difficult. Fluid and electrolyte losses can be profound and sustained in immunodeficient patients. The most frequent form of acute diarrheal disease in early childhood is rotavirus gastroenteritis. but a negative stool result does not exclude significant malabsorption. methodical process in these cases. Interestingly. Normal breastfed babies may have positive stool Clinitest® results. a readily available alternative rehydration solution.gastroenterology childhood malabsorption Figure 4. and trace elements. The normal stool pH is 6 or greater and should not have reducing substances present.aappublications. initial fever. rehydration can proceed with either the World Health Organization rehydration solution. live in underdeveloped countries. Affected children have acute diarrhea that is not sustained. There may be a secretory component of the diarrhea during the early phase of the infection. Lactose malabsorption can occur in children who experience severe gastroenteritis that involves significant and persistent diarrhea lasting longer than the usual 5 to 7 days. Long-term dietary restrictions are unnecessary for healthy children who did not have special dietary requirements antedating their diarrheal disease. Beverages that have a high sugar content should be avoided in children who have moderate-to-severe rotavirus diarrhea. Photo courtesy of Dr Frank R. vitamins. Cryptosporidium Infection with Cryptosporidium usually is an acute transitory problem. If necessary. have had repetitive bouts of diarrhea and digestive problems. as occurs in shock or necrotizing enterocolitis. Postinfectious Diarrhea Much effort has been undertaken to develop specialized formulas and rehydration solutions for children who have acute diarrheal dehydration. However. often employing predigested formulas administered via tube drip feedings or hyperalimentation. Giardia trophozoites in mucus overlying duodenal mucosa. 2013 . This is uncommon in previously healthy children on standard diets. Sinatra. Giardiasis is not a cause of bloody diarrhea. Young infants are particularly prone to developing intractable diarrhea if symptoms persist for longer than 2 to 3 weeks. The clinician can document lactose malabsorption by testing the stool for pH and for reducing substances by employing a modified Clinitest®. electrolytes. Most infants have some vomiting. malnutrition similar to those seen with celiac disease or CD. Their usual diet gen- erally can be reinstituted without problems shortly after the vomiting phase of the illness has subsided. Worsening malabsorption and malnutrition can become lethal. at Pakistan:AAP Sponsored on November 20. not just lactase. The brush border of proximal small intestinal enterocytes is injured in this infection. drinks well water. 4) or by antigen testing of stool.

6 June 2003 Downloaded from http://pedsinreview.24 No. 2013 .gastroenterology childhood malabsorption Figure 5. The hallmark of these disorders is the inability to remain normally hydrated on standard infant formulas or human at Pakistan:AAP Sponsored on November 20. Children who have sucrase-isomaltase deficiency develop symptoms when fed increasing amounts of sucrose and experience diarrhea.and macronutrient deficiencies result from voluminous diarrhea.aappublications. Dehydration and acidosis are severe. Intestinal mucosal biopsy enzyme biochemical analysis often is required for diagnosis. Congenital Intestinal Enterocyte Brush Border Enzyme Deficiencies Children who have congenital brush border digestive enzyme deficiencies or transport defects present with watery diarrhea and dehydration soon after birth. many patients have abnormal brush border ultrastructure on electron microscopy. The recent availability of specialized formulas. although the diarrhea usually is not severe. Postinfectious or congenital carbohydrate malabsorp- 202 Pediatrics in Review Vol. congenital lactase deficiency. The most frequent of these disorders are glucose-galactose transporter deficiency. ally have histologically normal-appearing small intestinal mucosa. Constitutional lactase deficiency typically surfaces in school-age children or with increasing age. Electron microscopy of child who has microvillous inclusion disease. However. In the latter. 5). These diseases are extremely rare because there has been natural selection for afflicted children not to survive. Children who have inherited absorptive defects usu- Figure 6. Note the defective brush border microvilli structure (A) and abortive microvillous membranes in cytoplasmic vacuoles in enterocytes (B). Affected children have significant amounts of acid and reducing substances in their stools. dum if the child is dehydrated. and abdominal discomfort. electron microscopy of intestinal mucosal biopsies demonstrates abortive microvillus structures in the enterocyte cytoplasm without a mature brush border (Fig. Secondary micro. Symptoms are similar to those of sucrase-isomaltase deficiency. and microvillus inclusion disease. bloating. hyperalimentation. The lactose in human milk does not seem to have a negative effect on realimentation. Subepithelial lymphatic bleb and villous clubbing in a child who has congenital intestinal lymphangiectasia. sucrase-isomaltase deficiency. and even small bowel transplantation has permitted longterm survival in some cases.

Affected patients have chronically elevated right-sided heart pressures. or from the thoracic duct into the systemic venous circulation can result in secondary intestinal lymphatic engorgement with fat malabsorption and PLE.24 No. Diagnosis is based on finding fat malabsorption.and medium-chain fatty acids can be absorbed and transported directly through the mesenteric venous blood to the liver. 2013 . ● ● ● ● Detailed history and physical examination Serially plotted points on growth chart Complete blood count. This problem can be severe and result in debilitating and life-threatening fluid. edema. bilirubin) Examination of stool and test for occult blood tion can be diagnosed indirectly by performing hydrogen breath tests employing the suspected malabsorbed carbohydrate. chemistry panel (albumin. Table 2. iron studies —Fat-soluble vitamin levels (vitamin E. low fat-soluble vitamin levels. As mentioned previously. Children who have CD.aappublications. and other neoplasms that obstruct lymphatic flow are susceptible to secondary intestinal lymphangiectasia. Patients have either generalized or asymmetric edema. First evident in young infants. short. Cases can be generalized or phenotypically expressed as selectively defective lymphatic circulation from the extremities or internal organs. prothrombin time) Stool Analysis ● ● ● ● ● FA1AT Stool trypsin Stain for dietary fat 3-day quantitative fecal fat pH and Clinitest for sugars Other ● ● Sweat test Hydrogen breath test for carbohydrate malabsorption Pediatrics in Review Vol. Management of children who have primary intestinal lymphangiectasia involves shifting the diet toward medium-chain dietary fat supplements and fat-soluble vitamin supplements and reducing dietary sodium to minimize edema. Screening Tests Blood Tests ● ● ● ● Inflammatory bowel disease panel Immunoglobulin A level and celiac panel Cystic fibrosis DNA mutation testing Vitamin levels —Vitamin B12. Secondary Intestinal Lymphangiectasia Secondary or acquired perturbation of intestinal lymphatic flow is a consequence of many disorders. The intestine commonly is at Pakistan:AAP Sponsored on November 20. the disorder often improves with time. Children also respond to diuretic therapy to mobilize peripheral edema. Supplemental dietary protein is useful in counteracting the affects of PLE.gastroenterology childhood malabsorption Initial Evaluation of Suspected Malabsorption Table 1. erythrocyte sedimentation rate. 25-OH D. The latter is common in congenital heart disease. children are born with defective lymphatics throughout the body. 6). especially after Fontan surgery for hypoplastic left heart syndrome. This disorder often is noticed initially in infants or in young children. Segmental involvement of the intestine is seen in some cases. It is believed that affected patients lack a cofactor necessary for the intestinal absorption of zinc. lymphatic tumors. Any impedance of lymphatic flow from the intestine. liver enzymes. We have found lymphatic scans to be very useful. A. Hydrogen breath analysis with the potential offending carbohydrate should be used cautiously in cases of profound malabsorption. Medical treatment includes dietary supplements of min- Abnormal Intestinal Lymphatic Drainage Primary Intestinal Lymphangiectasia Perturbation of lymphatic flow results in malabsorption of fat-soluble vitamins and long-chain dietary fats. but it may appear later in childhood. Fortunately. from abdominal lymphatics into the thoracic channels. A modified test using a reduced amount of the suspected offending sugar and preparedness for intravenous fluid administration is prudent. Genetic testing is available for some of these inherited defects. Acrodermatitis Enteropathica The exact pathogenesis of this disorder is uncertain. and abnormal lymphatic imaging studies. Human milk seems to ameliorate or prevent the problem. radiation enteritis. mycobacterial infections of the intestine. total protein. and mineral (Ca ⫹⫹) deficiencies as well as malnutrition. it results in profound zinc deficiency with severe rash. There is also profound PLE due to the engorged submucosal lymphatics in the small intestine (Fig. It sometimes is necessary to consider other surgical options or heart transplantation if medical treatment is not adequate. and mucocutaneous breakdown. PO4 electrolytes. folate.6 June 2003 203 Downloaded from http://pedsinreview. the presence of lymphopenia. Rarely. Ca. electrolyte.

Urman M. Gastrointestinal manifestations of cystic fibrosis. Further diagnostic radiographs. Holmes RD. can be considered. Pa: Lippincott Williams & Wilkins. An FA1AT is useful in screening for the many disorders that cause PLE. Cryptosporidium. Definitive endoscopic and histologic confirmation of such disorders as chronic ulcerative colitis.6 June 2003 Downloaded from http://pedsinreview.43:375–390 Lerner A. Lebenthal E. Pediatr Ann. Hyams JS. Routine laboratory screening tests are listed in Table 1. Pediatr Clin North Am. Rosenthal A. 1997. Am J Gastroenterol. A quantitative fecal fat assessment is one of the best methods of detecting generalized malabsorption. Celiac disease: going against the grains. Gastroenterol. scans. 1997. and a prothrom- bin time are useful both for screening for fat-soluble vitamin malabsorption and guiding therapy (Table 2). it is common to see undigested food in the stools of healthy infants and young children. 1996. 2001. 89:758 –761 204 Pediatrics in Review Vol. 1996. It presently is not standard care to establish these diagnoses based simply on the results of blood screening tests. Measurement of fat-soluble vitamin levels. 1996. eds.26:235–241 Sokol RJ. Chronic nonspecific diarrhea of childhood: pathophysiology and management. Castle VP. Philadelphia. Fasano A. Laboratory Diagnosis and Management Paramount in the initial management of a child who is believed to have malabsorption is a detailed history and physical examination. 23:673–705 Thomas DW.gastroenterology childhood malabsorption Other Definitive Diagnostic Testing Table 3. Tracking serial measurements on a growth chart is crucial. Short bowel syndrome in children and adults. In: DeAngelis CD. Sullivan B. Fornaroli F. Am Gastroenterol.96: 758 –765 Kneepkens CMF. Drago S. During the stool examination. Pediatr Clin North Am. the latter regarding possible cases of CD and small intestinal mucosal disorders such as celiac disease and intestinal lymphangiectasia. Lebenthal E. Catassi C. celiac panel. CD. Sinatra FR. Lerner A.113:1767–1778 Veligati LN. Protein-losing enteropathy. J Pediatr.130:474 – 478 Dubinsky MC. E. Clinical utility of serodiagnostic testing in suspected pediatric inflammatory bowel disease.43:125–155 Pietzak MM. and sweat test. infection (giardiasis. Gastrointestinal Endoscopy ⴙ Biopsy ● ● ● Special stains for celiac disease. Hoekstra JH. 2013 . Lagnas AN. Reversal of protein-losing enteropathy with heparin therapy in three patients with univentricular hearts and Fontan palliation. Gastroenterol Clin North Am. Other screening tests. Generalized malabsorption can be documented by obtaining a stool sample and staining for the presence of dietary fat in older children and adolescents or performing a 3-day quantitative stool fat test at any age. protein. Oski’s Principles and Practice of Pediatrics. Targan at Pakistan:AAP Sponsored on November 20. Ofman JJ. Treem WR. Burke G. Pediatr Clin North Am. and endoscopy. Chronic diarrhea and malabsorption. 3rd ed. are definitive (Table 3). Feigin RD.24 No. Management of malabsorption depends largely on the underlying disease Suggested Reading Branski D. Seidman EG. mycobacteria) Enzymology Electron microscopy/ultrastructure Endoscopic Retrograde Cholangiopancreatography/ Duodenal Intubation ● Pancreatic enzyme analysis Liver Biopsy Imaging Procedures ● ● ● ● Liver scan Radiolabeled Tc albumin lymphatic scan Computed tomography scanning of liver and pancreas Upper gastrointestinal radiographic series to rule out bowel stenosis or segmental dilation (bacterial overgrowth syndrome) erals. Fat soluble vitamins and their importance in patients with cholestatic liver diseases. and medium-chain triglycerides or hyperalimentation. 1999:1687–1689 Vanderhoof JA.aappublications. Branski D. such as an inflammatory bowel disease panel. including vitamins A. Delta 10 ppm versus delta 20 ppm: a reappraisal of diagnostic criteria for breath hydrogen testing in children. The mechanism for these medical therapies is unknown.16: 335–344 Riedel BD. Warshaw JB. and celiac disease is warranted. depending on the results of the aforementioned initial clinical evaluation and laboratory tests. 1994.43:307–331 Donnelly JP. 2001. 1994. Nutr Clin Pract. and 25-OH D. Some success has been achieved with either corticosteroids or low-dose heparin therapy. Pancreatic disease in children. 1997.

B. Vitamin B12. E. Long-chain triglycerides. Glucose. E. Intestinal lymphoma.pedsinreview. Medium-chain triglycerides. antigliadin IgG three times normal. and portal vein is: A. D. E. This result is most consistent with a diagnosis of: A. antitransglutaminase IgA weakly positive. Normal IgA. submucosal venules. Medium-chain triglycerides. Long-chain triglycerides. and chemistry panel. Absent IgA. A 30-month-old girl has failure to thrive that began toward the end of her first postnatal year. C. and thoracic duct is: A. physical examination. 6. other antibodies negative. E. Celiac disease.aappublications. Long-chain triglycerides. E. 8.24 No. A stool fecal alpha-1-antitrypsin excretion test you have ordered in the next phase of your evaluation is normal. erythrocyte sedimentation rate. D. The substance most likely to be absorbed and transported sequentially through the mucosa of the terminal ileum. D. Normal IgA. other antibodies negative. Vitamin B12.6 June 2003 205 Downloaded from http://pedsinreview. 2013 .gastroenterology childhood malabsorption PIR Quiz Quiz also available online at www. antigliadin IgA weakly negative. C. Glucose. Bile acids. Water. Bile acids. 10. C. Water. D. complete blood count. Absent IgA. B. other antibodies Medium-chain triglycerides. C. B. B. Bile acids. all antibodies negative. at Pakistan:AAP Sponsored on November 20. You are examining a 22-month-old boy who has steatorrhea and whose failure to thrive remains unexplained after history. 9. Primary intestinal lymphangiectasia. Normal IgA. Inflammatory bowel disease. C. (Continued) Pediatrics in Review Vol. and portal vein is: A. submucosal lacteals. other antibodies negative. 7. antigliadin IgG weakly positive. Cystic fibrosis. submucosal venules. The combination of celiac panel results that best predicts histologic changes compatible with celiac disease is: A. The substance most likely to be absorbed and transported sequentially through the mucosa of the proximal small intestine. The substance most likely to be absorbed and transported sequentially through the mucosa of the proximal small intestine. D.

Beginning an elemental medium-chain triglyceride-containing formula.gastroenterology childhood malabsorption 11. Eliminating fruit at Pakistan:AAP Sponsored on November 20. A previously healthy 2-month-old girl developed acute vomiting and diarrhea. C. occasionally containing undigested food particles. each day for the past 3 weeks. soy protein.6 June 2003 Downloaded from http://pedsinreview. Placing him on clear liquids for a few days. B. Rotavirus infection. You have seen him twice during that time. Her current intractable diarrhea is most likely a consequence of: A.24 No. D. Zinc deficiency. He has been otherwise asymptomatic and has lost no weight. E. B. Removing wheat. resulting in severe dehydration. cow milk. findings on the physical examination are unremarkable. her diarrhea continues and studies document intolerance of lactose. sucrose. Three weeks later.aappublications. and barley. Adding a daily multivitamin tablet. C. An enzyme-linked immunosorbent assay for Giardia was negative. The most appropriate next step is to alter the diet by: A. His physical examination results are normal. E. Shwachman syndrome. His appetite is normal. 2013 . D. rye. His stool is free of blood. 206 Pediatrics in Review Vol. Primary intestinal lymphangiectasia. Aside from malnutrition. Microvillus inclusion disease. and fat. 12. A previously well 14-month-old boy has had several watery stools.

aappublications. Thomas Pediatrics in Review 2003.aappublications. 2013 References This article cites 10 Subspecialty Collections This article.xhtml Reprints Information about ordering reprints can be found online: http://pedsinreview.aappublications. appears in the following collection(s): Nutrition Eating Disorders http://pedsinreview. can be found at: at Pakistan:AAP Sponsored on November rs_sub Permissions & Licensing Information about reproducing this article in parts (figures.195 DOI: Downloaded from http://pedsinreview. Pietzak and Dan W.Childhood Malabsorption Michelle M.24-6-195 Updated Information & Services including high resolution figures. tables) or in its entirety can be found online at: 0 of which you can access for free at: http://pedsinreview.aappublications. along with others on similar topics.1542/pir.