Pediatric Malabsorption Syndromes Workup

The following laboratory studies are indicated in malabsorption syndromes:

• Stool analysis

  • The presence of reducing substances indicates that carbohydrates have not been properly absorbed. One common mistake, especially with the use of superabsorbent diapers, is to test the solid portion of the stool instead of the liquid portion. Furthermore, in stools that are not fresh, bacterial hydrolysis, removal of the reducing substances, and artifactual reduction of pH occur.

  • Acidic stool has a pH level of less than 5.5. This indicates carbohydrate malabsorption, even in the absence of reducing substances.

  • Normally, stool bile acids should not be detected. If bile acid malabsorption is suspected, quantitative conjugated and unconjugated bile acids may be measured in stool, although this test is not routinely available and is not used in routine clinical practice.

  • The level of quantitative stool fat and the amount of fat intake should be measured and monitored for 3 days. Normal fat absorption depends on age (lower in the neonate) and improves throughout the first year of life to the reference range levels of 95% or higher. Moderate fat malabsorption ranges from 60-80%. Fat absorption of less than 50% indicates severe malabsorption.

  • The presence of large serum proteins in the stool, such as a₁ -antitrypsin, indicates leakage of serum protein and serves as a screening test for protein-losing enteropathy.

  • Examination of the stool for ova and parasites or testing for the stool antigen may reveal the presence of Giardia species, a known cause of acquired malabsorption syndromes in children who are usually older than 2 years.

  • Testing for other chronic intestinal infections that cause malabsorption, such as Clostridium difficile (assays for toxins A and B) or Cryptosporidium species (modified acid-fast examination of stool), may be performed.

• Urinalysis

  • Urine examination may reveal an unusually high concentration of the malabsorbed substance because, in many cases, the kidney and the gut use the same transporter.

  • In glucose-galactose malabsorption, the urinary glucose level is typically elevated when the serum glucose level is within reference range because of congenital malfunction of SGLT-1.

  • levels of urinary 4-hydroxyphenylacetic acid have been demonstrated to be elevated in the urine of children with bacterial overgrowth syndrome.

• Other laboratory studies

  • A CBC count may reveal megaloblastic anemia in patients with folate and vitamin B-12 malabsorption or neutropenia in patients with Shwachman-Diamond syndrome (associated with pancreatic insufficiency). In patients with abetalipoproteinemia, blood smears may reveal acanthocytosis.

  • Total serum protein and albumin levels may be lower than reference range in syndromes in which protein is lost or is not absorbed, particularly in protein-losing enteropathy and pancreatic insufficiency or enterokinase deficiency, respectively.

  • In children with untreated celiac disease, calcium metabolism defects are common and typically return to normal after gluten-free diet. Hence, a detailed, time-consuming, and expensive study of bone metabolism does not appear warranted in children who follow the gluten-free diet.

  • With fat malabsorption or ileal resection, fat-soluble vitamin levels in the serum are lower than reference range.

  • With bile acid malabsorption, levels of the low-density lipoprotein (LDL) cholesterol may be lower than reference range. Another method used to test for bile acid malabsorption is the SeHCAT scanning test. ^[9] Laboratories using this test have shown that bile acid malabsorption is not infrequent in adults with irritable bowel syndrome that presents with chronic diarrhea. ^[10]

  • In patients with inflammatory bowel disease, the erythrocyte sedimentation rate, C-reactive protein level, or both are commonly elevated. The value of numerous serological markers of inflammatory bowel diseases (eg, antisaccharomyces cerevisiae antibody [ASCA], perinuclear antineutrophil cytoplasmic autoantibodies [pANCA]) has been repeatedly confirmed in adults, in whom their specificity appears elevated, ^[11] but has not been convincingly demonstrated in children.

  • In patients with liver or biliary disease, the results of liver function tests may be higher than reference range levels. These tests include assays for alanine aminotransferase (ALT), aspartate aminotransferase (AST) in hepatitis, g-glutamyltransferase (GGT), alkaline phosphatase, and bilirubin in cholestatic liver disease.

  • Immunoglobulin G (IgG) and immunoglobulin A (IgA) antigliadin and IgA antiendomysial antibodies, or especially tissue transglutaminase antibodies, are useful in the diagnosis of gluten-sensitive enteropathy.

  • Enterocyte, smooth muscle, thyroid, and islet cell serum antibodies are revealed in patients with autoimmune enteropathy.

  • Recently, a 13C-Sucrose breath test has been proposed as a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine. ^[12]

Although upper GI radiography with small bowel follow-through demonstrates a pattern of thickened folds and increased fluid content in the jejunal loops in celiac disease and conditions characterized by protein-losing enteropathies, this test is no longer used because it is unspecific and not sensitive enough, especially when compared with other diagnostic tests.

Procedures include the following:

• Substance tolerance test

  • Attempt to isolate the substance that is causing the malabsorption. Resolution of diarrhea after the suspected substance is removed from the diet and resumption of the diarrhea when the substance is reintroduced are specific signs that the particular substance is not adequately absorbed.

  • If diarrhea does not resolve when the particular substance is removed from the diet, this does not necessarily indicate intolerance to the substance.

  • Malabsorption of certain nutrients can result in secondary intestinal damage and secondary malabsorption, which may no longer be related to the malabsorbed substance. Thus, this technique has low sensitivity until mucosal injury has had a chance to heal.

  • Challenging the patient with the suspected malabsorbed substance once the diarrhea has resolved provides a more sensitive test.

• Carbohydrate malabsorption tolerance test

  • Carbohydrate malabsorption results in bacterial fermentation. This biochemical process releases hydrogen gas that is absorbed into the blood and excreted by the lungs. Thus, different breath tests have been developed for malabsorption syndromes suspected of being related to carbohydrate malasborption. ^[13]

  • Under normal conditions, fermenting bacteria reside in the large intestine. When the bacteria in the large intestine ferment the carbohydrate load, an increase in the level of exhaled hydrogen is detected.

  • The amount of carbohydrate administered is typically 2 g/kg, with a maximum dose of 50 g. When testing for lactose tolerance, using a more physiologic amount (eg, 12.5-25 g) may be preferable.

  • An increase in the exhaled hydrogen concentration following ingestion of an oral carbohydrate load (>20 ppm) indicates carbohydrate malabsorption. Bacterial overgrowth in the small intestine results in an additional early rise in the exhaled hydrogen concentration and remains the most readily available test for this condition. ^[14]

  • Antibiotic administration within the 2 weeks prior to the test may cause false-negative results in this test.

• D-xylose absorption test

  • Another time-honored test for carbohydrate malabsorption is the D-xylose absorption test. Xylose is a pentose that is passively absorbed by the jejunal mucosa.

  • A standard dose of 5 g or, alternatively, 14.5 g/m² (maximum dose of 25 g) of D-xylose is orally administered as a 10% solution in water. The test result is positive in the following instances:

    • Children who weigh less than 30 kg - Serum level at 1 hour after ingestion is less than 25 mg/dL.

    • Children who weigh more than 30 kg - The 5-hour urinary excretion is less than 15%.

    • A positive test result suggests malabsorption due to proximal small bowel mucosal lesion (enteropathy).

    • Beware of false-positive results (eg, from delayed gastric emptying, small bowel bacterial overgrowth, accelerated transit time).

• Mucosal biopsy

  • This test is fundamental in obtaining a definitive diagnosis in many circumstances, such as common celiac disease. Almost all pediatric gastroenterology centers obtain biopsies of the duodenal mucosa during an upper endoscopy.

  • Moderate villous atrophy may be seen in protein-sensitive enteropathies, Giardia infection, or bile acid malabsorption.

  • Histologic examination of the biopsy tissue may reveal the mucosal inclusions seen in abetalipoproteinemia, eosinophilic gastroenteritis, Wolman disease, or congenital microvillous atrophy, for which electron microscopy is needed.

  • Functional assays of the biopsy tissue assess carbohydrate disaccharidase enzymes.

Biopsy of the small intestine remains the criterion standard for the diagnosis of celiac disease.

The classic features include villous atrophy, infiltration of the epithelium by cytotoxic intraepithelial T lymphocytes, and crypt hyperplasia. However, the spectrum can range from a simple intraepithelial lymphocytosis without villous blunting or crypt hyperplasia to total villous atrophy with severe crypt hyperplasia.