Dietary carbohydrates are comprised of polysaccharides (starch), disaccharides (sucrose and lactose) and traces of monosaccharides. Polysaccharides first undergo intraluminal digestion by salivary and pancreatic amylases. The hydrolysis of disaccharides occurs at the intestinal brush border by the disaccharidases sucrase-isomaltase, maltase and lactase. The monosaccharides glucose, galactose and fructose are then absorbed into the enterocyte by simple or facilitated diffusion or by a sodium carrier-mediated active transport. From the enterocyte, monosaccharides diffuse into the vascular circulation.

Symptoms of carbohydrate malabsorption are characterized by gaseous distention, borborygmi, cramps and watery nonbloody diarrhea having an acidic pH (4.0-5.5) and containing unabsorbed reducing sugars. The most common cause of carbohydrate malabsorption in infancy is lactase deficiency secondary to viral gastroenteritis. However, lactase deficiency may also complicate any disease that disrupts the small intestinal brush border, including celiac disease, Crohn's disease and HIV enteropathy. Congenital lactase deficiency, sucrase-isomaltase deficiency and other inherited deficiencies of brush-border enzymes are extremely rare. In each case simply excluding the malabsorbed carbohydrate from the diet will promptly resolve the symptoms.

Protein digestion begins in the stomach, where gastric acid causes protein denaturation and activates pepsin. In the small intestine brush border, enterokinase converts pancreatic trypsinogen into trypsin which, in turn, activates the pancreatic enzymes chymotrypsin and elastase. Digested protein in the form of free amino acids, di- and tripeptides is rapidly absorbed into the enterocyte and then into the circulation. In contrast to carbohydrate malabsorption, diseases that significantly disrupt the intestinal mucosa do not result in protein malabsorption. Rather, in cases of severe gastroenteropathy, intestinal protein loss develops because of a "back-leak" of protein from the systemic circulation across the damaged bowel wall into the intestinal lumen - aptly termed a protein-losing enteropathy.

The digestion of fat begins in the stomach, where fundal lipase hydrolyzes medium- and long-chain fats. This phase of fat digestion is particularly important in neonates whose pancreatic lipase activity is relatively low compared with the mature adult. In the duodenum, hydrophobic long-chain triglycerides are first emulsified by bile salts and then hydrolyzed by pancreatic lipase. Free fatty acids and monoglycerides solubilize into micelles and approach the luminal surface, where they then diffuse across the enterocyte cell membrane. In the enterocyte the free fatty acids and monoglycerides are re-esterified and packaged along with apoprotein B-48 into chylomicrons. Chylomicrons are excreted via the intercellular spaces into the lymphatic circulation, and then through the thoracic duct into the systemic circulation. In contrast to long-chain fats, medium-chain triglycerides are water-soluble and are absorbed by the enterocyte directly into the bloodstream. Medium-chain triglycerides therefore do not require bile salts for digestion or an intact lymphatic system for circulation.

With fat malabsorption the stools are greasy, soft but not liquid, foul smelling and bulky. Growth failure is a dominant feature, because the intestinal loss of high-energy fat nutrients (9 kcal/g of fat) leads to a profound deficiency in the total calories absorbed daily. In addition to the steatorrhea and failure to thrive, the clinical manifestations of fat-soluble vitamin deficiency (vitamins A, D, E, K) may also be present.

A complete history and thorough physical examination are the necessary first steps for establishing a diagnosis of malabsorption and sorting out the potential etiologies. Diarrhea is often a principal clinical symptom, and it is important to determine by the history whether steatorrhea is present. The duration, fluidity, frequency, size, consistency and color of the stools should be documented. Another cardinal presenting symptom for malabsorption is weight loss. However, since failure to thrive in infancy is most often secondary to poor dietary intake, it is critical to obtain a complete dietary history. The physician should ask about the quantity and type of formula the infant is receiving or whether the child is breastfed. The age at which new foods were introduced should be established and the physician should try to ascertain whether there is any correlation between the onset of symptoms and the dietary modifications. The average daily caloric intake should be estimated. Consultation with a pediatric dietitian can be very helpful with this assessment. The physician should inquire about the child's growth and review the record of the child's weight and height. These should be plotted on standard infant growth curves.

A complete birth history should also be obtained. All neonatal complications or prior abdominal surgery should be documented. For a patient who presents with a family history of similar gastrointestinal complaints or with gastrointestinal complaints and a background of consanguinity, an underlying genetic disorder should be considered. Information about travel or recent contacts may help to exclude infectious etiologies. A history of frequent infections may point to an underlying immunodeficiency disorder. Recurrent pulmonary disease might suggest a diagnosis of cystic fibrosis.

On physical examination, accurate measurements of the child's current weight, height and head circumference should be obtained and plotted on a standard pediatric growth curve graph along with all previous measurements. The physician should examine the head, eyes, mouth and tongue, looking for features of fat-soluble or water-soluble vitamin or trace mineral deficiencies. For example, pallor and cheilosis might implicate an iron deficiency anemia. Alopecia may be a feature of zinc deficiency. The cardiovascular and pulmonary examination should be thorough. Abdominal distention may be a manifestation of organomegaly or intestinal gas. Buttock wasting and excess skin folds, particularly in the groin, are features of subcutaneous fat loss. Edema of the lower extremities may develop with hypoalbuminemia. Clubbing may occur in celiac disease or inflammatory bowel disease.

7.4.1 BASELINE STUDIES

The stools should be analyzed for leukocytes and blood which, if present, suggest a colitis. Determination of the stool pH and a search for reducing substances will support or exclude a diagnosis of carbohydrate malabsorption. A stool smear staining positively for fat globules or fat crystals suggests the presence of fat malabsorption. It is useful to obtain a complete blood count. Iron deficiency anemia may be associated with celiac disease, inflammatory bowel disease or cow's milk protein intolerance. Megaloblastic anemia is a feature of folate or B₁₂ deficiency. Acanthocytes are the hallmark of abeta-lipoproteinemia. The presence of eosinophilia may support a diagnosis of milk protein intolerance. Low serum protein and albumin are features of a protein-losing enteropathy. A urinalysis and urine culture should be obtained to exclude an occult urinary tract infection. Infants and children who present with failure to thrive despite a sufficient caloric intake should have a sweat test to screen for cystic fibrosis.

If fat malabsorption is suspected, the gold standard test is a 72-hour stool collection for fat. In this instance a complete and accurate 72-hour dietary history must be obtained concomitantly with the three-day stool collection so that the coefficient of fat absorption can be calculated. Infants less than 6 months of age should absorb >85% of fat intake. By one year of age the fat absorption should be at an adult level of >95%.

D-xylose is a sugar that is absorbed by the intestinal enterocyte independent of brush-border enzymes or pancreatic function. The D-xylose test is used to assess the integrity of the intestinal mucosa. A standard dose of D-xylose is given by mouth, and a serum level is drawn one hour later. A level greater than 25 mg/dL is normal. A low one-hour serum level suggests mucosal damage. The usefulness of this test in the evaluation of malabsorption is controversial.

The breath hydrogen test is most often used to diagnose lactose malabsorption. In this instance a standard dose of lactose is given by mouth and serial breath samples are obtained. If lactose is malabsorbed, colonic bacteria ferment the sugar, producing hydrogen ion, which is subsequently absorbed by the colon into the blood, circulated to the lungs and then exhaled. A significant rise in breath hydrogen 60-90 minutes after lactose ingestion is consistent with incomplete lactose absorption. Hydrogen breath tests may also be used for the diagnosis of sucrase deficiency or small intestinal bacterial overgrowth.

Contrast radiographic studies are useful to exclude congenital anatomical abnormalities of the gastrointestinal tract as a cause for the malabsorption. Ulceration and strictures are features of Crohn's disease. Intestinal dilation and hypomotility support a diagnosis of bacterial overgrowth.

Upper endoscopy with multiple biopsies permits both gross and microscopic assessment of the intestinal mucosa. The histologic features of a small intestinal biopsy may be highly indicative or even diagnostic for the etiology of the malabsorption. The diagnosis of celiac disease is established only by an intestinal biopsy. The presence of fat-laden vacuoles in intestinal villus cells suggests a disorder in the delivery phase of fat digestion, such as abeta-lipoproteinemia or hypobetalipoproteinemia. The histological presence of dilated lacteals is a feature of lymphangiectasia.

There are a few basic principles to the management of the pediatric patient who presents with a malabsorption syndrome. First, it is important to determine the cause of the disorder and direct treatment accordingly. For example, patients with celiac disease recover on a gluten-free diet. Infants with cow's milk protein allergy respond to a modification of the protein in the diet. The manifestations of secondary lactase deficiency will resolve with a lactose-free formula or with the use of enzyme supplements (Lactaid^®). The fat malabsorption in cystic fibrosis is corrected with pancreatic enzyme replacement. Second, it is usually necessary to provide ample supplemental calories in order to achieve catch-up growth. A good supply of extra calories is especially important for the young infant with marked failure to thrive. High-calorie formulas are frequently introduced early, often before a specific diagnosis has been established. Third, any vitamin, mineral and trace element deficiencies should be corrected. Anemias are treated with the appropriate supplements. Fat-soluble vitamins are required for infants with ongoing steatorrhea, especially those with cholestatic liver disease. Vitamin B₁₂ supplementation may be necessary for patients with ileal resection.