Mal Absorbtion

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DOI: 10.1542/pir.24-6-1952003;24;195Pediatrics in Review

Michelle M. Pietzak and Dan W. ThomasChildhood Malabsorption

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Childhood MalabsorptionMichelle M. Pietzak, MD,*

Dan W. Thomas, MD† Objectives After completing the article, readers should be able to:1. Explain why congenital mucosal malabsorptive defects almost always present in early

infancy with massive diarrhea and dehydration.

2. Name the extraintestinal signs or symptoms that many children who have underlying

chronic digestive disorders might have without specific digestive complaints.

3. Describe the procedure for distinguishing pancreatic or other intraluminal causes of

malabsorption from intestinal mucosal absorptive defects.

4. Delineate the specific signs with which generalized malabsorption frequently is

associated.

IntroductionThe dilemma of determining whether a child has malabsorption is common in clinical

practice. Important signs include malodorous stools, chronic diarrhea, failure to thrive,

weight loss, and subnormal growth. There may be other signs of severe malnutrition, such

as edema, rickets, excessive bleeding or bruising, decreased muscle mass, or a “potbelly.”

Gastrointestinal dysfunction is linked inexorably as a possible cause of failure to thrive.

Nevertheless, the clinician initially should attempt to determine whether failure to thrive is

related to a deficient diet, malabsorption, or abnormal energy utilization. A thorough

history, detailed dietary intake, assessment of the family environment, and complete

physical examination usually suggest one of these three causes. The child’s height, weight,

and head circumference (for infants) should be plotted serially on a growth chart. The

physical examination also may reveal other phenotypic findings consistent with congenitaldisorders associated with suboptimal growth and nutrition (eg, Russell Silver syndrome).

Other clinical details are useful in the evaluation for malabsorption. For example, there

is a frequent misconception that children who have malabsorption experience chronic

diarrhea. However, many children who have malabsorptive disorders have loose stools only

occasionally or no diarrhea. Conversely, children who have watery stools may not have

significant gastrointestinal dysfunction. Many of these otherwise healthy children drink

excessive amounts of sweetened beverages and are labeled as having toddler’s diarrhea.

These children often drink excessive amounts of juices in child care facilities or at a

baby-sitter’s.

Follow-up assessment may reveal dietary discrepancies or clinical findings, such as a

goiter, systolic hypertension, and tremor suggestive of a thyroid disorder; evolving anemia,

short stature, and occasional diarrhea in a teen who has

Crohn disease (CD); or a loss of developmental milestones

and organomegaly in a child who has a lipid storage disorder.

Epidemiology and PathophysiologyNutrient absorption is an efficient process that is regional-

ized in the gut and depends on pancreatic and hepatobiliary

secretory function. Overall gastrointestinal function depends

on development but is relatively efficient at birth. Neonates

and young infants have a reduced ability to digest fat because

*Assistant Professor of Clinical Pediatrics and Medical Director, Nutrition Support Team.†Associate Professor of Pediatrics and Head, Gastroenterology, Keck School of Medicine, University of Southern California,

Childrens Hospital Los Angeles, Los Angeles, CA.

Abbreviations

CD: Crohn disease

CF: cystic fibrosis

Ig: immunoglobulin

PLE: protein-losing enteropathy

FA1AT: fecal alpha-1-antitrypsin excretion test

Article gastroenterology

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of developmental delay in pancreatic and hepatobiliary

function. Consequently, healthy infants may have visible

fat in their stools. Development of coordinated intestinal

peristalsis is important in facilitating digestion. Peristaltic

abnormalities are common in preterm infants and very ill

children.

The digestive and absorptive process usually is cate-

gorized into intraluminal, mucosal, and venous and lym-

phatic transport phases. The fate of each of the major

nutrients, including carbohydrates, fats, proteins, vita-

mins, minerals, electrolytes, and water, is characterized

separately in terms of these digestive phases. Most nutri-

ent digestion and absorption occurs in the proximal small

intestine. There is bulk flow of water through the porous

junctions of the proximal small intestinal epithelial cells.

However, vitamin B12 and bile acids are absorbed selec-

tively in the terminal ileum. Malabsorbed bile acids are

deleterious to the colonic mucosa because of their deter-

gent action, which is capable of causing colitis and diar-

rhea. This is especially true for children who have disor-

ders of the terminal small bowel, such as CD, but even

more so in children who have short bowel syndrome.

FatsPancreatic and hepatobiliary secretions mix with nutri-

ents in the duodenum and proximal jejunum to result in

the digestion of dietary fat. Dietary fats are emulsifiedintraluminally within small digestive packets called mi-

celles, which facilitate mixing with pancreatic enzymes.

Intraluminal dietary fat digestion produces long-chain

fatty acids that are absorbed and repackaged into chylo-

microns by epithelial cells. Chylomicrons are transported

via lymphatics to the venous circulation and eventually to

the liver for metabolism and repackaging. Short- or

medium-chain fatty acids are digested and absorbed by a

similar process, but are transported directly to the liver

via mesenteric venous blood flow. This difference in the

absorptive process allows enhancement of energy absorp-

tion of dietary fat by supplementation with medium-chain triglycerides. Examples of disorders that result in a

defective intraluminal phase of digestion are pancreatic

insuf ficiency due to cystic fibrosis (CF) and hepatobiliary

dysfunction associated with biliary atresia.

Carbohydrates Watery, loose stools usually occur because of malab-

sorbed carbohydrate or other osmotically active sub-

stances. The mucosal phase of digestion typically is de-

fective in cases of carbohydrate malabsorption. The

osmotic properties of malabsorbed carbohydrate lead to

excessive accumulation of intraluminal fluid and diar-

rhea. In addition, ileocolonic bacteria ferment malab-

sorbed dietary sugars and carbohydrates into simple sug-

ars, organic acids (eg, short-chain fatty acids), and gases.

Methane, carbon dioxide, and hydrogen are common

gaseous by-products. These fermentative by-products

can be used to detect carbohydrate malabsorption.

A noninvasive test quantifies the amount of hydrogen

that is produced by gut fermentation in exhaled air

(hydrogen breath test). Carbohydrate malabsorption

may be due to excessive intake, any cause of mucosal

damage, short bowel syndrome, or congenital intestinal

transport or enzyme deficiencies.

As mentioned, malabsorption of carbohydrates results

in excessive fermentation by bacteria in the distal ileum

and colon. Hence, the colon can serve as a “stopgap”

digestive organ. This occurs normally in breastfed in-

fants. However, the colon is an important adjunctive

digestive organ in children who have small bowel diges-

tive dysfunction or short bowel syndrome.

ProteinNature 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. The significant malabsorption that

occurs in patients who have CF can result in azotorrhea.

The hypoproteinemia that occurs in some children whoare undernourished and have generalized malabsorption

usually is not because of azotorrhea, but rather is due to

a combination of deficient dietary intake and excessive

intestinal protein loss termed protein-losing enteropathy

(PLE).

Numerous causes of PLE generally are attributable to

intestinal damage or impediment of mesenteric lym-

phatic or venous flow. Although the exact mechanisms

for PLE are not known, it generally occurs because of

excessive weeping of serum protein into the bowel be-

yond what subsequently can be digested and reabsorbed

downstream in the gut. Children who have intraluminalmalabsorptive defects, as in CF, do not have PLE because

their digestive defect does not involve mucosal damage.

Hence, a screening test for PLE, such as the fecal alpha-

1-antitrypsin excretion test (FA1AT), is useful in distin-

guishing intraluminal from mucosal maladies. An ele-

vated FA1AT result suggests a disorder such as celiac

disease or CD rather than CF or liver disease.

Cotransport of NutrientsCodependency of nutrient absorption is common. Ex-

amples include the competitive absorption of zinc and

copper and the cotransporter for sodium and glucose.

gastroenterology childhood malabsorption

196 Pediatrics in Review Vol.24 No.6 June 2003




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Pharmacologic amounts of zinc can impede copper ab-

sorption from the gut in patients who have excessive

tissue accumulation of copper due to Wilson disease.

Elucidation of the intestinal sodium-glucose cotrans-

porter was instrumental in advancing knowledge of the

physiology of salt and water absorption. This spurred

development of present day oral rehydration solutions

for acute diarrheal dehydration. The sodium-glucose

cotransporter is well preserved during gastrointestinal

infections. Glucose, salt, and water absorption can be

maintained by feeding a child who has acute viral gastro-

enteritis a balanced glucose and electrolyte solution that

contains optimal molar ratios of salt and glucose. Oral

fluids that contain excessive salt or sugar are ineffective

and are likely to cause osmotic diarrhea and free water

loss.

Bacterial Overgrowth SyndromeDisorders of intestinal peristalsis and other causes of gut

stasis often result in malabsorption. Stasis allows bacterial

overgrowth that can deplete the

body of vitamin B12 and other

minerals and nutrients as well as

causing steatorrhea. Affected pa-

tients frequently have macrocytic

anemia, bloating, and diarrhea.

Rare motility disorders are a causeof this syndrome, but most pa-

tients have a history of congenital

gut anomalies or prior gastroin-

testinal surgery. Intestinal bacte-

ria generally are commensal, and the “good” bacteria in

the distal small intestine and colon are beneficial. These

organisms help ferment undigested nutrients and main-

tain distal bowel integrity. For example, vitamin K and

folate are produced and made available for absorption

from nutrients in the diet by intestinal bacterial metabo-

lism.

Secretory DiarrheaThis condition not only results in fluid and electrolyte

losses, but in malabsorption if prolonged and severe.

Secretory diarrhea is encountered more often in children

who have short bowel syndrome, severe gastrointestinal

mucosal injury, secretory tumors (eg, carcinoid syn-

drome, neuroblastoma, or Zollinger-Ellison syndrome),

or as a result of a toxin produced from a gastrointestinal

pathogen. Cholera is the prototype infection capable of

producing a toxin that causes severe secretory diarrhea.

The hallmark of secretory diarrhea is voluminous, watery

stools despite bowel rest. The electrolyte content of stool

ef fluent approaches that of serum. Hypokalemia occurs

frequently in association with secretory neoplasms. In

these clinical situations, the phases of digestion remain

generally intact, but the gut is overcome by the massive

ef flux of fluid and salt.

Causes of Malabsorptive SyndromesPancreatic Disorders

CF is one of the most common serious malabsorptive

disorders. CF is caused by mutations in the CFTR gene,

which is located on chromosome 7 at position 7q31. The

most common mutation is Delta F508, but hundreds of

other mutations have been identified. Many mutations

are undetected by genetic screening. The reported inci-

dence of CF in Caucasians in the United States ranges

from 1 in 2,000 to 4,000 live births. Approximately 1 in

25 Caucasians carries at least one CF DNA mutation;

these individuals are asymptomatic. It has been conjec-

tured that certain CF DNA mutations, even when het-

erozygotic, may predispose to chronic liver or pancreatic

disease. This remains to be substantiated. CF is rare but

does occur in noncaucasians.

The primary pathophysiologic abnormality in CF is

defective chloride channel function that results in gener-

alized dysregulation of salt and water flux across epithe-

lial glandular cells. There is multiorgan involvement,

with characteristic disease of lung and pancreas and vari-

able disease in the gastrointestinal tract, hepatobiliary system, and the reproductive tract. Disease results from

inspissated plugging by proteinaceous secretions in af-

fected organs. Long-term complications include cirrho-

sis, obstipation (distal intestinal obstruction syndrome),

and diabetes. Although most patients who have lung

disease and pancreatic insuf ficiency have the Delta F508

mutation, further research is needed to determine asso-

ciations between specific CFTR mutations and pheno-

typic disease expression.

The most common presentation of CF is an infant

who has persistent cough, congestion, and failure to

thrive. The stools are bulky or sometimes loose. Some

Children who have cystic fibrosisdo not have protein-losing enteropathy; thosewho have celiac disease have an elevatedfecal alpha 1-antitrypsin excretion test.






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affected neonates have cholestasis or meconium ileus.

Meconium ileus is a consequence of the tenacious meco-

nium that accumulates in the terminal ileum and proxi-

mal colon in utero; its incidence in CF is about 20%. The

bowel can be twisted and become atretic in utero. 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.

Many children who have CF do not present in early

infancy and have clinical signs related to primary organ

involvement later in life. We have cared for school-age

children who have CF and present initially with acute

pancreatitis. Similarly, children who have recurrent lungproblems may not have any other signs of this disorder

and are diagnosed later in life. Very young infants who

have CF can have generalized edema without other

symptoms. We recently cared for a 3-year-old African-

American and a teenage Caucasian who had rectal pro-

lapse as their primary clinical problem and subsequently

were found to have CF. Although CF is part of the

differential diagnosis of rectal prolapse, also included are

rectal polyp, intussusception, infections and infestations

causing proctocolitis, severe malnutrition, and the most

frequent cause, severe functional constipation.

CF usually is diagnosed by performing a sweat chlo-ride test. Sweat test results may be false-positive in adre-

nal insuf ficiency, ectodermal dysplasia, nephrogenic dia-

betes insipidus, glycogen storage disease, anorexia

nervosa, hypoparathyroidism, inherited cholestasis, mal-

nutrition, hyperthyroidism, and other very rare condi-

tions. False-negative results can occur with malnutrition

and generalized edema and in very young infants who

have CF. CF DNA mutation tests can be obtained, but as

mentioned, this testing may miss some cases. Other

presumptive diagnostic tests include assessing for the

presence of inspissated proteinaceous material in tissue

biopsies, transnasal conductance measurements, andtests for pancreatic insuf ficiency. The test performed

most easily for pancreatic insuf ficiency in a young infant

is the semiquantitative test for trypsin in the stool. This

test is not useful for older children and adults. Pancreatic

enzyme levels also can be measured by direct endoscopic

sampling of ductal secretions from the ampulla of Vater.

These procedures are dif ficult to perform and usually are

unnecessary.

Aside from signs of malabsorption, children who have

any chronic lung condition, sinusitis, nasal polyps, rectal

prolapse, unexplained digital clubbing, meconium ileus,

unexplained chronic liver disease or chronic pancreatitis,

or unexplained failure to thrive and infants who have

hypoproteinemia and edema should be screened for CF.Two syndromic conditions are among the other, less

frequent causes of pancreatic insuf ficiency. Shwachman

syndrome is estimated to occur in 1 in 10,000 live births.

The exact cause of this autosomal recessive disorder is

not yet known. The phenotypic features include short

stature, skeletal abnormalities, recurrent infections, and

various forms of bone marrow dysfunction, including

pancytopenia and cyclic neutropenia. The pancreatic,

bone marrow, and skeletal abnormalities are due to

hypoplasia and other embryologic mesenchymal abnor-

malities. The Johanson-Blizzard syndrome occurs less

frequently than Shwachman syndrome but is anotherrecognized cause of childhood pancreatic insuf ficiency

and malabsorption. Patients characteristically have gas-

trointestinal anomalies (imperforate anus), peculiar

whorls of tissue in their scalps, absent nasal cartilage,

deafness, and hypothyroidism. The pancreatic insuf fi-

ciency is due to fatty replacement, and diabetes may

occur.

Chronic Cholestasis As discussed previously, any hepatobiliary disorder that

results in chronic cholestasis can cause steatorrhea. Con-sequently, children who have chronic cholestasis often

experience growth failure, chronic malnutrition, and fat-

soluble vitamin deficiencies. Vitamin E deficiency is of

special concern because several interrelated digestive

steps are necessary for absorption of this vitamin. Signs of

vitamin E deficiency include ataxia, decreased or absent

deep tendon reflexes, ocular palsy, and hemolytic ane-

mia. Patients often have abnormal vitamin K malabsorp-

tion and reduced hepatic synthesis of coagulation factors.

Children who have chronic cholestasis or any form of

chronic malabsorption should be screened for fat-soluble

vitamin deficiencies.Chronic cholestasis is evident to the practitioner be-

cause of the child’s enlarged liver and jaundice. Most

children who have persistent cholestasis from early in-

fancy have biliary atresia. There also are rare conditions

that are either syndromic or related to specific inherited

bile duct epithelial transport defects. There may be a

family history or other syndromic features. Alagille syn-

drome is one of the more common syndromic cholestatic

disorders. Affected children also have congential heart

disease (usually peripheral pulmonic stenosis), short stat-

ure, phenotypic facial features, and skeletal and rib ab-

normalities.






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Gastrointestinal Mucosal Surface Injury:Celiac Disease

Clinicians have been aware of the existence of celiac

disease for centuries. The overall incidence worldwide is

uncertain, but is believed to be far greater than previous

estimates of 1 in 4,000. It is very common in Northern

European and Scandinavian countries, with a frequency

of 1 in 100 to 500, and a similar estimated incidence in

the United States, based on recent prospective studies.

The disease results from progressive inflammatory dam-

age to small bowel mucosa, with the enteritis appearingto be most severe proximally. Symptoms range from

severe diarrhea and malnutrition to a paucity of clinical

complaints. Extraintestinal problems are common.

Celiac disease, sometimes called gluten-sensitive en-

teropathy, sprue, nontropical sprue, or celiac sprue, is

becoming the prototypic model for autoimmune disease.

The disorder appears in genetically susceptible individu-

als who sustain an autoimmune reaction to the toxic

gliadin protein fraction of gluten. There is a strong trend

for inheritance with certain identified susceptibility risk

factors. More than 99% of affected people are positive for

human leukocyte antigen-DQ2 or -DQ8.Gluten protein is derived from a group of cereal grains

that include wheat, rye, and barley. Pure oats probably

should not be considered an offending agent, although

oats in the United States usually are milled with other

grains that contaminate the mixture with gluten and may

cause problems. Rice and corn are not offending agents.

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 gluten-

containing diet (Figs. 1 and 2). Patients should undergo

intestinal biopsy based on symptoms, family history, and

the results of antibody screening tests. In the past, serial

biopsies were recommended when the patient was both

on and off gluten to document a histologic response, but

this no longer is recommended unless the diagnosis is

uncertain. Immunohistochemical stains of biopsies can

be performed to enhance diagnostic accuracy (Fig. 3).

The clinical presentation of celiac disease can vary,

with extraintestinal manifestations predominating. The

classic case is the infant who has a “potbelly,” wasted

extremities, bulky stools, irritability, and laboratory evi-

dence of malabsorption. These youngsters do not neces-sarily have diarrhea, and some are constipated. There are

more subtle presentations, asymptomatic forms, and

delayed-onset disease. Because extraintestinal disease

and malabsorption occur, some children have musculo-

skeletal abnormalities, short stature, delayed puberty,

and dental defects. Patients also may have recurrent

aphthoid oral lesions. Infertility and a history of sponta-

neous abortions are encountered in undiagnosed

women. Curiously, a link has been shown between celiac

disease and epilepsy, schizophrenia, depression, and cen-

tral nervous system calcifications. Behavioral changes and

emotional lability are common.There is a strong association between celiac disease

and other autoimmune disorders. Research at our center

suggests an incidence of celiac disease of 1 in 12 patients

who have type 1 diabetes. Celiac disease also is more

common in autoimmune thyroid disorders, rheumatoid

arthritis, and other vasculitic disorders. We also have

encountered a few patients who had initial autoimmune

liver disease and later were found to have celiac disease.

Patients who have celiac disease have laboratory evi-

dence of generalized malabsorption and anemia. It is not

uncommon for affected patients to have a complex ane-

mia from iron, folate, or vitamin B12 deficiencies. In

Figure 1. Normal intestinal mucosal biopsy. Photo courtesy of

Dr Frank R. Sinatra.

Figure 2. Severe celiac disease with total villous atrophy of

the duodenal mucosa, lymphocytic infiltrate, and marked crypthyperplasia.






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severe cases, there is malabsorption of fat-soluble vita-

mins and hypoproteinemia. Fecal alpha-1-antitrypsin ex-

cretion is abnormal because of PLE.

Presently, screening blood tests consist of antigliadin

immunoglobulin G (IgG) and IgA, antiendomysial IgA,

and antitissue transglutaminase IgA antibodies. Affected

patients may have serum IgA deficiency. For this reason,

we usually obtain a serum IgA level. Suggestive positive

screening results include the presence of more than onepositive antibody test without IgA deficiency. A positive

IgG antigliadin antibody test and IgA deficiency also are

suggestive, especially in the presence of clinical symp-

toms or a family history. 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. The latter finding is nonspecific and suggests

increased gut permeability and possible underlying

bowel disorder.

Treatment of celiac disease hinges on implementation

of a lifelong gluten-free diet. Some patients feel that

partial compliance is adequate to control their symp-

toms, but they are still at increased risk for gastrointesti-

nal cancers and extraintestinal medical problems. These

include infertility, psychological and neurologic prob-

lems, and osteoporosis.

Crohn DiseaseJust as for celiac disease, the clinical presentation of CD is

varied and sometimes very subtle. Because CD may affect

any part of the digestive system or body, multiple differ-

ent clinical pictures are possible. Malabsorption can

range from lactose intolerance in some patients because

of generalized small bowel mucosa injury to severe gen-

eralized nutrient malabsorption due to full-thickness

bowel injury with dysmotility and bleeding. Intestinal

strictures can cause bacterial overgrowth syndrome. The

anemia associated with CD can be multifactorial, encom-

passing iron, folate, and vitamin B12 deficiencies. The

latter is common in CD because of the predilection for

the terminal ileum. Patients who have CD also may

experience malabsorption due to rapid intestinal transit.

The profound digestive effects of this illness ultimately

can result in growth failure, delayed puberty, and vitamin

and trace element deficiencies.

PLE is common in CD. In a retrospective study of

patients at our center, we found the FA1AT to be themost common initial abnormal laboratory test; more

than 90% of patients had evidence of PLE. Other useful

screening tests include a complete blood count (high

white blood cell count or anemia), erythrocyte sedimen-

tation rate (high), and stool test for occult blood (posi-

tive).

A high index of suspicion as well as the availability of

blood screening tests for inflammatory bowel disease

should prevent longstanding macro- and micronutrient

deficiencies in children who have subtle signs of CD.

Newer screening blood tests include perinuclear anticy-

toplasmic antibody (usually positive in ulcerative colitis)and antisaccharomyces cerevisiae antibody (frequently

positive in CD).

Infectious Diarrhea: GiardiasisChronic giardiasis often masquerades as other digestive

disorders. Giardia trophozoites can infest healthy chil-

dren chronically, but usually this is a clinical problem in

debilitated or immunodeficient children. Youngsters

who have selective IgA deficiency are particularly suscep-

tible to persistent giardiasis. Patients experience intermit-

tent symptoms of bloating, diarrhea, and bulky stools;

they also may have subnormal growth and other signs of

Figure 3. Stain for CD3-positive intraepithelial lymphocytes

in a diabetic child who had chronic intermittent diarrhea and

positive celiac antibody screening tests. This technique helpsto detect cases of celiac disease when typical histologicfeatures of villous atrophy are absent.






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malnutrition similar to those seen with celiac disease or

CD. Giardiasis is not a cause of bloody diarrhea. The

diagnosis is made by finding the organism on proximal

intestinal biopsy (Fig. 4) or by antigen testing of stool.

The latter is a reliable and widely available clinical test.

Clinicians should have a high index of suspicion for

giardiasis in children who have persistent diarrhea if the

child attends child care, drinks well water, lives near or

visits lakes or streams, or has lived in or visited under-

developed regions.

CryptosporidiumInfection with Cryptosporidium usually is an acute tran-

sitory problem, although severe outbreaks have been

reported in young healthy children. Affected children

have acute diarrhea that is not sustained. As with giardi-

asis, patients who have acquired and congenital immune

deficiencies are susceptible to a prolonged and debilitat-

ing diarrheal illness that is characterized by malabsorp-

tion of fluid, electrolytes, vitamins, and trace elements.

The diarrhea is usually watery and nonbloody. Fluid and

electrolyte losses can be profound and sustained in im-

munodeficient patients. The response to treatment is variable and inconsistent. Diagnosis is made by selective

examination of the stool for Cryptosporidium or identifi-

cation of the organism in the ef fluent or mucosal biopsies

from the proximal small bowel.

Postinfectious DiarrheaMuch effort has been undertaken to develop specialized

formulas and rehydration solutions for children who

have acute diarrheal dehydration. However, most previ-

ously healthy children who have acute diarrheal illnesses

with or without dehydration are not likely to have sus-

tained gastrointestinal dysfunction. Their usual diet gen-

erally can be reinstituted without problems shortly after

the vomiting phase of the illness has subsided. If neces-

sary, rehydration can proceed with either the World

Health Organization rehydration solution, a readily

available alternative rehydration solution, or a commer-

cial solution. Long-term dietary restrictions are unneces-

sary for healthy children who did not have special dietary

requirements antedating their diarrheal disease.

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. This is uncommon in previously healthy children

on standard diets. Similarly, children who have pre-

existing digestive disorders, live in underdeveloped

countries, have had repetitive bouts of diarrhea and

digestive problems, and have other serious medical ill-

nesses are susceptible to secondary lactose malabsorp-

tion. This stems from mucosal damage that results in loss

of the lactase enzyme on the intestinal brush border. In

these cases, specialized diets or lactose-free formulas are

necessary. The clinician can document lactose malab-

sorption by testing the stool for pH and for reducing

substances by employing a modified Clinitest®. The nor-

mal stool pH is 6 or greater andshould not have reducing

substances present. Normal breastfed babies may have

positive stool Clinitest® results, but a negative stool

result does not exclude significant malabsorption. Chil-dren who have profound intestinal damage, as occurs in

shock or necrotizing enterocolitis, can have deficiencies

of most brush border enzymes, not just lactase. Young

infants are particularly prone to developing intractable

diarrhea if symptoms persist for longer than 2 to 3 weeks.

Worsening malabsorption and malnutrition can become

lethal. Secondary acquired milk and soy formula allergies

make management dif ficult. Realimentation is a slow,

methodical process in these cases, often employing pre-

digested formulas administered via tube drip feedings or

hyperalimentation.

The most frequent form of acute diarrheal disease inearly childhood is rotavirus gastroenteritis. Most infants

have some vomiting, initial fever, and watery diarrhea.

The brush border of proximal small intestinal enterocytes

is injured in this infection. The diarrhea often is classified

as osmotic because of malabsorption of dietary sugars

and carbohydrates. There may be a secretory component

of the diarrhea during the early phase of the infection.

Beverages that have a high sugar content should be

avoided in children who have moderate-to-severe rotavi-

rus diarrhea. Interestingly, infants who are breastfed do

relatively well with continuation of breastfeeding in ad-

dition to supplemental oral rehydration solution ad libi-

Figure 4. Giardia trophozoites in mucus overlying duodenal

mucosa. Photo courtesy of Dr Frank R. Sinatra.






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dum if the child is dehydrated. The lactose in human milk

does not seem to have a negative effect on realimenta-

tion.

Congenital Intestinal Enterocyte Brush BorderEnzyme Deficiencies

Children who have congenital brush border digestive

enzyme deficiencies or transport defects present with

watery diarrhea and dehydration soon after birth. Dehy-dration and acidosis are severe. Secondary micro- and

macronutrient deficiencies result from voluminous diar-

rhea. Affected children have significant amounts of acid

and reducing substances in their stools. The hallmark of

these disorders is the inability to remain normally hy-

drated on standard infant formulas or human milk. These

diseases are extremely rare because there has been natural

selection for af flicted children not to survive. The recent

availability of specialized formulas, hyperalimentation,

and even small bowel transplantation has permitted long-

term survival in some cases.

Children who have inherited absorptive defects usu-

ally have histologically normal-appearing small intestinal

mucosa. However, many patients have abnormal brush

border ultrastructure on electron microscopy. Intestinal

mucosal biopsy enzyme biochemical analysis often is

required for diagnosis. The most frequent of these disor-

ders are glucose-galactose transporter deficiency, con-

genital lactase deficiency, sucrase-isomaltase deficiency,and microvillus inclusion disease. In the latter, electron

microscopy of intestinal mucosal biopsies demonstrates

abortive microvillus structures in the enterocyte cyto-

plasm without a mature brush border (Fig. 5). Children

who have sucrase-isomaltase deficiency develop symp-

toms when fed increasing amounts of sucrose and expe-

rience diarrhea, bloating, and abdominal discomfort,

although the diarrhea usually is not severe. Constitu-

tional lactase deficiency typically surfaces in school-age

children or with increasing age. Symptoms are similar to

those of sucrase-isomaltase deficiency.

Postinfectious or congenital carbohydrate malabsorp-

Figure 5. Electron microscopy of child who has microvillous

inclusion disease. Note the defective brush border microvilli

structure (A) and abortive microvillous membranes in cyto-plasmic vacuoles in enterocytes (B).

Figure 6. Subepithelial lymphatic bleb and villous clubbing in

a child who has congenital intestinal lymphangiectasia.






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erals, protein, and medium-chain triglycerides or hyper-

alimentation. Some success has been achieved with either

corticosteroids or low-dose heparin therapy. The mech-

anism for these medical therapies is unknown.

Laboratory Diagnosis and ManagementParamount in the initial management of a child who is

believed to have malabsorption is a detailed history and

physical examination. Tracking serial measurements on a

growth chart is crucial. Routine laboratory screening

tests are listed in Table 1. During the stool examination,

it is common to see undigested food in the stools of

healthy infants and young children. Generalized malab-

sorption can be documented by obtaining a stool sample

and staining for the presence of dietary fat in olderchildren and adolescents or performing a 3-day quanti-

tative stool fat test at any age.

A quantitative fecal fat assessment is one of the best

methods of detecting generalized malabsorption. An

FA1AT is useful in screening for the many disorders that

cause PLE. Measurement of fat-soluble vitamin levels,

including vitamins A, E, and 25-OH D, and a prothrom-

bin time are useful both for screening for fat-soluble

vitamin malabsorption and guiding therapy (Table 2).

Other screening tests, such as an inflammatory bowel

disease panel, celiac panel, and sweat test, can be consid-

ered, depending on the results of the aforementioned

initial clinical evaluation and laboratory tests. Further

diagnostic radiographs, scans, and endoscopy, the latter

regarding possible cases of CD and small intestinal mu-

cosal disorders such as celiac disease and intestinal lym-

phangiectasia, are definitive (Table 3). Definitive endo-

scopic and histologic confirmation of such disorders as

chronic ulcerative colitis, CD, and celiac disease is war-

ranted. It presently is not standard care to establish these

diagnoses based simply on the results of blood screening

tests. Management of malabsorption depends largely on

the underlying disease

Suggested ReadingBranski D, Lerner A, LebenthalE. Chronic diarrhea andmalabsorp-

tion. Pediatr Clin North Am. 1996;43:307–331Donnelly JP, Rosenthal A, Castle VP, Holmes RD. Reversal of

protein-losing enteropathy with heparin therapy in three pa-tients with univentricular hearts and Fontan palliation. J Pedi- atr. 1997;130:474– 478

Dubinsky MC, Ofman JJ, Urman M, Targan SR, Seidman EG.

Clinical utility of serodiagnostic testing in suspected pediatricinflammatory bowel disease. Am J Gastroenterol. 2001;96:758–765

Kneepkens CMF, Hoekstra JH. Chronic nonspecific diarrhea of childhood: pathophysiology and management. Pediatr Clin North Am. 1996;43:375–390

Lerner A, Branski D, Lebenthal E. Pancreatic disease in children.Pediatr Clin North Am. 1996;43:125–155

Pietzak MM, Catassi C, Drago S, Fornaroli F, Fasano A. Celiacdisease: going against the grains. Nutr Clin Pract. 2001;16:

335–344Riedel BD. Gastrointestinalmanifestations of cystic fibrosis. Pediatr

Ann. 1997;26:235–241Sokol RJ. Fat soluble vitamins and their importance in patients with

cholestatic liver diseases. Gastroenterol Clin North Am. 1994;23:673–705

Thomas DW, Sinatra FR. Protein-losing enteropathy. In: DeAnge-lis CD, Feigin RD, Warshaw JB, eds. Oski’s Principles and Practice of Pediatrics . 3rd ed. Philadelphia, Pa: Lippincott Wil-liams & Wilkins; 1999:1687–1689

Vanderhoof JA, Lagnas AN. Short bowel syndrome in children and

adults. Gastroenterol. 1997;113:1767–1778 Veligati LN, Treem WR, Sullivan B, Burke G, Hyams JS. Delta 10

ppm versus delta 20 ppm: a reappraisal of diagnostic criteria forbreath hydrogen testing in children. Am Gastroenterol. 1994;89:758–761

Table 3. Other DefinitiveDiagnostic Testing

Gastrointestinal Endoscopy Biopsy

● Special stains for celiac disease, infection (giardiasis,Cryptosporidium, 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 (bacterialovergrowth syndrome)




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PIR Quiz

Quiz also available online at www.pedsinreview.org.

6. The substance most likely to be absorbed and transported sequentially through the mucosa of the proximalsmall intestine, submucosal lacteals, and thoracic duct is:

A. Bile acids.B. Glucose.C. Long-chain triglycerides.D. Medium-chain triglycerides.E. Vitamin B12.

7. The substance most likely to be absorbed and transported sequentially through the mucosa of the proximalsmall intestine, submucosal venules, and portal vein is:

A. Bile acids.B. Long-chain triglycerides.C. Medium-chain triglycerides.D. Vitamin B12.E. Water.

8. The substance most likely to be absorbed and transported sequentially through the mucosa of the terminalileum, submucosal venules, and portal vein is:

A. Bile acids.B. Glucose.C. Long-chain triglycerides.D. Medium-chain triglycerides.E. Water.

9. You are examining a 22-month-old boy who has steatorrhea and whose failure to thrive remainsunexplained after history, physical examination, complete blood count, erythrocyte sedimentation rate, andchemistry panel. A stool fecal alpha-1-antitrypsin excretion test you have ordered in the next phase of your evaluation is normal. This result is most consistent with a diagnosis of:

A. Celiac disease.B. Cystic fibrosis.C. Inflammatory bowel disease.D. Intestinal lymphoma.E. Primary intestinal lymphangiectasia.

10. A 30-month-old girl has failure to thrive that began toward the end of her first postnatal year. The

combination of celiac panel results that best predicts histologic changes compatible with celiac disease is:A. Absent IgA, antigliadin IgG three times normal, other antibodies negative.B. Absent IgA, all antibodies negative.C. Normal IgA, antigliadin IgA weakly negative, other antibodies negative.D. Normal IgA, antigliadin IgG weakly positive, other antibodies negative.E. Normal IgA, antitransglutaminase IgA weakly positive, other antibodies negative.

(Continued)






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11. A previously healthy 2-month-old girl developed acute vomiting and diarrhea, resulting in severedehydration. Three weeks later, her diarrhea continues and studies document intolerance of lactose,sucrose, cow milk, soy protein, and fat. Aside from malnutrition, findings on the physical examination areunremarkable. Her current intractable diarrhea is most likely a consequence of:

A. Microvillus inclusion disease.B. Primary intestinal lymphangiectasia.C. Rotavirus infection.D. Shwachman syndrome.E. Zinc deficiency.

12. A previously well 14-month-old boy has had several watery stools, occasionally containing undigestedfood particles, each day for the past 3 weeks. You have seen him twice during that time. His appetite isnormal. He has been otherwise asymptomatic and has lost no weight. His physical examination results arenormal. His stool is free of blood. An enzyme-linked immunosorbent assay for Giardia was negative. Themost appropriate next step is to alter the diet by:

A. Adding a daily multivitamin tablet.B. Beginning an elemental medium-chain triglyceride-containing formula.C. Eliminating fruit juices.D. Placing him on clear liquids for a few days.E. Removing wheat, rye, and barley.






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DOI: 10.1542/pir.24-6-1952003;24;195Pediatrics in Review

Michelle M. Pietzak and Dan W. ThomasChildhood Malabsorption

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