DISORDERS OF MALABSORPTION

All disorders of malabsorption are associated with diminished intestinal absorption of

one or more dietary nutrients. Malabsorption can result from a defect in the nutrient digestion
in the intestinal lumen or from defective mucosal absorption. Almost all the malabsorption
disorders are accompanied by chronic diarrhea which further worsens the malabsorption.
Categorized into:
 Malabsorption of multiple nutrients
 Malabsorption of specific nutrients (carbohydrates, fat, protein, vitamins, minerals, and
trace elements)

Clinical Approach

Common presenting features especially in toddlers:

 Diarrhea
 Abdominal distention
 Failure to gain weight with a fall in growth chart percentiles
o Muscle wasting
o Disappearance of subcutaneous fat with subsequent loose skinfolds
The nutritional consequences of malabsorption are more dramatic in toddlers because of the
limited energy reserves and higher proportion of calorie intake being used for weight gain and
linear growth. In older children, malnutrition can result in growth retardation (e.g. Celiac
disease). If malabsorption is left untreated, linear growth slows, and with prolonged
malnutrition, death can follow.

Nutritional assessment is an important part of clinical evaluation in children with malabsorptive

disorders.
 Vitamin D malabsorption – reduced bone mineral density and metabolic bone disease,
which increases risk of bone fractures.
 Vitamin K malabsorption – coagulopathy
 Protein-losing enteropathy – hypoalbuminemia and edema
 Iron malabsorption – microcytic anemia and low reticulocyte count, low serum folate
levels
 Fat malabsorption – low serum Vitamin A and Vitamin E concentrations

Diarrhea is the main clinical expression of malabsorption. Onset and Nature must be identified.
 Onset of diarrhea in early infancy – Congenital defect
 Explosive water diarrhea – Carbohydrate Malabsorption
 Loose, bulky stools – Celiac Disease
 Pasty and Yellowish offensive stools – Exocrine Pancreatic Insufficiency.
Stool color is usually not helpful; green stool with undigested “peas and carrots” can suggest
rapid intestinal transit which is a self-limiting condition unassociated with failure to thrive.

Secretory Diarrhea such as in Congenital Chloride Diarrhea and Microvillus Inclusion disease,
stool is watery and voluminous and can be mistaken for urine. Onset of symptoms after
introduction of a particular food into a child’s diet can provide diagnostic clues.

*Read Table 338-3 for Diarrheal Diseases Appearing in the Neonatal Period*
EVALUATION OF CHILDREN WITH SUSPECTED INTESTINAL MALABSORPTION

Initial work-up should include

 Stool cultures
 Antibody tests for parasites
 Stool microscopy for ova and parasites such as Giardia
 Stool occult blood and leukocytes to exclude inflammatory disorders
 Stool pH
 Quantitative stool fat examination to demonstrate fat malabsorption
 Alpha-1 Antitrypsin to demonstrate protein malabsorption
 Fecal stool elastase-1 can determine exocrine pancreatic insufficiency
 CBC with Peripheral Smear
 Serum IgA and TG2 antibody levels for Celiac Disease

Investigations for Carbohydrate Malabsorption

 Uses Clinitest reagent to identify reducing substances
 Acidic stool with >2+ reducing substance – carbohydrate malabsorption
 Breath hydrogen test – identifies specific carbohydrate that is malabsorbed
o A rise in breath hydrogen of 20ppm above the baseline is considered a positive test.
o The child should not be on antibiotics at the time of the test because colonic flora is
essential for fermenting sugar.
 Small bowel mucosal biopsies can measure mucosal disaccharidase concentrations directly.
o Primary enzyme deficiency – mucosal enzymes low, small bowel mucosal
morphology normal
o Celiac disease -- partial or total villous atrophy

Investigations for Fat Malabsorption

 Ability to assimilate fat varies with age
o Premature infant – can absorb only 65-75% of dietary fat
o Full term infant – absorbs almost 90%
o Older child – absorbs >95% of fat
 Quantitative determination requires 3-day stool collection and determination of coefficient
of fat absorption:
o Coefficient of fat absorption = (Fat Intake – Fecal Fat losses) x 100
Fat Intake
o Expensive and unpleasant to perform
 Acid Steatocrit test is the most reliable
 Serum concentrations of Vitamins A, D, E, K
 Prolonged PTT is an indirect test to assess vitamin K deficiency

Investigations for Protein-Losing Enteropathy

 Excessive bowel protein loss usually manifests as hypoalbuminemia.
 Urinary protein excretion must be determined to differentiate from renal disorder.
 Stool Alpha1-antitrypsin is a useful screening test.
Investigations for Exocrine Pancreatic Function
 Cystic Fibrosis is the most common cause of exocrine pancreatic insufficiency in children
o Sweat Chloride test must be performed
 Fecal elastase-1 is a sensitive test to assess exocrine pancreatic function in chronic cystic
fibrosis and pancreatitis but cannot identify between primary and secondary nature and can
also give a false positive result during acute episodes of diarrhea.
 Serum trypsinogen concentration as a screening test can also be used.

Investigations for Intestinal Mucosal Disorders

 Requires histologic examination of small bowel mucosal biopsies obtained during endoscopy.
 PAS staining – to assess congenital microvillus atrophy

Imaging procedures
 Plain radiographs
 Barium contrast studies

CELIAC DISEASE (GLUTEN-SENSITIVE ENTEROPATHY)

 Immune mediated systemic disorder elicited by gluten and relatated prolamines in
genetically susceptible individuals and characterized by presence of a variable combination
of gluten-dependent clinical manifestations.
 Triggered by ingestion of wheat gluten and related prolamines from rye and barley.
 Failure to thrive
 Chronic diarrhea
 Vomiting
 Abdominal distention
 Muscle wasting
 Anorexia
 Irritability
 Constipation
 Rectal prolapse or Intussusception
 Most common extraintestinal manifestiation – Iron Deficiency Anemia unresponsive to
iron therapy
Clinical Spectrum of Celiac Disease
SYMPTOMATIC
Frank malabsorption symptoms:
 Chronic Diarrhea
 Failure to thrive
 Weight loss
Extraintestinal manifestations:
 Anemia
 Fatigue
 Hypertransaminasemia
 Neurologic disorders
 Short stature
 Dental enamel defects
 Arthralgia
 Aphthous stomatitis
SILENT
No apparent symptoms in spite of histologic evidence of villous atrophy

LATENT
Subjects who have normal histology, but at some other time, before or after, have shown gluten-
dependent enteropathy

POTENTIAL
Subjects with positive celiac disease serology but without evidence of altered jejunal histology
Might or might not be symptomatic

Diagnosis
 Anti-TG2 IgA antibodies
 Total IgA serum levels

Treatment
 The only treatment is lifelong strict adherence to a gluten-free diet.
 Wheat-, Barley-, and Rye-free diet

OTHER MALABSORPTIVE SYNDROMES

Congenital Intestinal Mucosal Defects

MICROVILLUS INCLUSION DISEASE (CONGENITAL MICROVILLUS ATROPHY)

 Autosomal recessive disorder, which manifests at birth with profuse watery secretory
diarrhea
 Light microscopy of small bowel mucosa shows diffuse thinning with hypoplastic villus
atrophy and no inflammatory infiltrates
 Diagnosed by light microscopy using PAS and CD10 staining which shows very thin or absent
brush border
 No causal treatment exists for MVID
 Intestinal transplantation is the only definitive treatment for this rare disease.

TUFTING ENTEROPATHY (CONGENITAL TUFTING ENTEROPATHY)

 Manifests in the 1st few weeks of life with persistent water diarrhea
 Distinctive feature on small intestinal mucosal biopsy is focal epithelial “tufts” (tear-drop
shaped groups of closely packed enterocytes with apical rounding of plasma membrane)
involving 80-90% of epithelial surface.
 No treatment has been effective, so management requires permanent parenteral nutrition
with possible intestinal transplantation

ENTERIC ANENDOCRINOSIS
 Mutations of NEUROG3 gene produce
 Generalized mucosal malabsorption
 Vomiting
 Diarrhea
  Failure to thrive
 Dehydration
 Hyperchloremic metabolic acidosis.
 Oral alimentation with anything other than water produces diarrhea
 Treatment: TPN and Small bowel transplantation

PROPROTEIN CONVERTASE 1/3 DEFICIENCY

 Autosomal recessive
 Chronic watery, neonatal onset diarrhea is described in infants with
o Hyperinsulinism
o Hypoglycemia
o Hypogonadism
o Hypoadrenalism
 Subsequent onset of marked obesity with hyperphagia in the toddler years
 Elevated serum levels of proinsulin are highly supportive

CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME AND ENTEROCYTE HEPARAN SULFATE

DEFICIENCY
 “Congenital disorders of glycosylation” or “Carbohydrate-deficient glycoprotein (CDG)”
 genetic disorders of assembly of N-glycans in the cytosol and ER
 associated with protein-losing enteropathy.
 Diagnosis:
o Serum transferrin
o Enzyme analysis
o DNA analysis
 Treatment: Oral mannose
 Congenital enterocyte heparin deficiency is a rare cause of intractable diarrhea with protein-
losing enteropathy

SYNDROMIC DIARRHEA
 Also known as phenotypic diarrhea or trichohepatoenteric syndrome
 A congenital enteropahy manifestaing with early onset of severe diarrhea requiring
parenteral nutrition
 Patients are born small for gestational age and present with diarrhea starting in the 1 st 6
months of life (<1month of age in most cases)
 Facial dysmorphism with prominent forehead, broad nose, and hypertelorism
 Distinct abnormality of hair, trichorrhexis nodosa
 Hairs are wooly, easily removed, and poorly pigmented
 Café-au-lait on lower limbs
 Liver disease
 Cardiac abnormalities
 Colitis
 Congenital hemochromatosis
 Microscopic analysis shows twisted hair (pili torti)
 Histopath analysis: nonspecific villus atrophy with or without mononuclear cell infiltration
 Extraintestinal autoimmune disorders include arthritis, membranous glomerulonephritis,
insulin-dependent DM, thrombocytopenia, autoimmune hepatitis, hypothyroidism, and
hemolytic anemia.
 Treatment based on T-cell-suppressive immunomodulation
o Steroid pulse therapy
o Calcineurin-dependent immunosuppressive drugs (tacrolimus)

BILE ACID MALABSORPTION

 Mutation of ileal sodium-bile acid cotransporter gene, SLC10A2, results in congenital
diarrhea
 Steatorrhea
 interruption of enterohepatic circulation of bile acids
 reduced plasma cholesterol levels.

INTESTINAL LYMPHANGIECTASIA
 Congenital form – associated with lymphatic abnormalities elsewhere in the body
 Secondary lymphangiectasia – constrictive pericarditis, heart failure, retroperitoneal fibrosis,
abdominal tuberculosis, and retroperitoneal malignancies.
 Diagnosis: Elevated fecal alpha1-antitrypsin clearance.
 Radiologic findings: uniform, symmetric thickening of mucosal folds throughout the small
intestine
 Treatment
o Restricting amount of long-chain fat ingested
o Administering formula containing protein and medium-chain triglycerides

ABETALIPOPROTEINEMIA
 Bassen-Kornzweig syndrome
 Rare autosomal recessive disorder of lipoprotein metabolism
 Associated with severe fat malabsorption from birth
 Children fail to thrive during first year of life
 Stools are pale, foul smelling, and bulky
 Distended abdomen
 DTRs are absent
 Slow intellectual development
 Diagnosis: (+)acanthocytes in the peripheral blood smear and extremely low plasma levels of
cholesterol (<50mg/dL); LDL fraction is virtually absent from the circulation
 Specific treatment not available
 Large supplements of Vitamins ADEK should be given

HOMOZYGOUS HYPOBETALIPOPROTEINEMIA
 Autosomal dominant
 Homozygous form is indistinguishable from abetalipoproteinemia

Homozygous Hypobetalipoproteinemia Abetalipoproteinemia

Plasma LDL Reduced Normal
CHYLOMICRON RETENTION DISEASE (ANDERSON DISEASE)
 Rare recessive disorder
 Defect in chylomicron exocytosis from enterocytes
 Sar1b is defective
 Steatorrhea
 Chronic Diarrhea
 Failure to thrive
 Plasma cholesterol moderately reduced
 Fasting Triglycerides normal
 Fat soluble vitamins (A and E) are low
 Treatment: early aggressive therapy with fat-soluble vitamins and modification of dietary fat
intake

WOLMAN DISEASE
 Rare, lethal lipid storage disease that leads to lipid accumulation in multiple organs,
including small intestine due to deficiency in lysosomal acid lipase
 Vomiting
 Severe Diarrhea
 Hepatosplenomegaly
 Steatorrhea
 Treatment: Long-term bone marrow engraftment

DGAT1 MUTATION
 Two siblings in one family with severe protracted diarrhea starting at 3 days of age had loss-
of-function homozygous splice mutations in the diacylglycerol acyltransferase (DGAT1) gene
that catalyzies the final step in the synthesis of triglycerides.

INTESTINAL INFECTIONS AND INFESTATIONS ASSOCIATED WITH MALABSORPTION

POSTINFECTIOUS DIARRHEA
 In infants and very young toddlers, chronic diarrhea can appear following infectious enteritis,
regardless of the nature of the pathogen
 Treatment is supportive

BACTERIAL OVERGROWTH
 Can result from clinical conditions that alter gastric pH or small bowel motility, including
disorders such as partial bowel obstruction, diverticula, intestinal failure, intestinal
duplications, DM, and scleroderma.
 Prematurity, Immunodeficiency, and Malnutrition are other RFs associated with this disease
 Diagnosis: Culturing small bowel aspirate or by lactulose hydrogen breath test.
 Treatment: correction of underlying causes
 Oral administration of antibiotic is the mainstay therapy
o Metronidazole for 2-4 weeks

TROPICAL SPRUE
 Etiology of this disease is unclear because it follows outbreaks of acute diarrheal disease and
improves with antibiotic therapy.
 Fever
 Malaise
  Watery diarrhea
 Severe malnutrition (glossitis, stomatitis, cheilosis, night blindness, hyperpigmentation,
and edema
 Megaloblastic anemia
 Diagnosis: small bowel biopsy
 Treatment: Nutritional supplementations
o Folate
o Vitamin B12

WHIPPLE DISEASE
 Chronic systemic infectious disorder
 Rare disease especially in childhood
 Caused by Tropheryma whipplei which can be cultured from a lymph node in involved tissue
 Diarrhea
 Abdominal pain
 Weight loss
 Joint pains
 Neurologic changes
 Involvement of Eyes, Heart, and Kidneys
 Diagnosis: PAS-positive macrophage inclusion in biopsy material
 Treatment: Cotrimoxazole for 1-2 years
 2-week course of IV Ceftriaxone or Meropenem followed by Cotrimoxazole for 1 year is
recommended

IMMUNODEFICIENCY DISORDERS
 Malabsorption can occur with congenital immunodeficiency disorders, and chronic diarrhea
with failure to thrive is often the mode of presentation
 Immunodeficiencies such as hypogammaglobulinemia in pediatric age group are more often
secondary to other conditions such as cancer and chemotherapy, chronic infections,
malabsorption, nephrotic syndrome, or cardiac disease.
 Malnutrition, diarrhea, and failure to thrive are common in untreated children with HIV
 Cryptospiridium can cause chronic secretory diarrhea
 Cancer chemotherapy can damage bowel mucosa leading to secondary malabsorptopn of
disaccharides such as lactose.
 After BMT, mucosal damage from graft-versus-host disease can cause diarrhea and
malabsorption