Malabsorption in Children
Eyad Altamimi, MD
Pediatric Gastroenterologist
Assistant Professor of Pediatrics
Mu`tah University
Malabsorption vs. Maldigestion
Decreased intestinal absorption of
macronutrients and/or micronutrients
 “malabsorption” – defect in mucosal phase
 “maldigestion” – defect in intraluminal phase
Normal Digestion and Absorption
 Mechanical mixing
 Enzyme and bile salt
production
 Mucosal function
 Blood supply
 Intestinal motility
 Commensal gut flora
Fat Digestion and Absorption
Carbohydrate and Protein
Digestion and Absorption
Pancreatic proteases
Mucosal peptidases
Protein  Oligopeptides  AA
Digestion
Absorption
Distribution
CHO  Oligosaccharides  Sugars
Pancreatic amylase
Mucosal disaccharidases
Misconception
Malabsorption=Chronic Diarrhea
But many have loose motions
Classification of Malabsorption
 Luminal
 Mucosal
 Postabsorptive
Case 1
 14 month old F with FTT
 Watery diarrhea x 2 months; 3-10 episodes per day; stool
infectious work-up: negative
 No nausea, vomiting, abdominal pain, abdominal distention,
hematochezia, melena
 No improvement in symptoms with change to soy milk
 No significant PMH or FH
 PE: Pale skin, abdomen distended but soft and nontender, normal
bowel sounds, no organomegaly
Growth
Chart
Labs
• WBC 14.1, Hgb 9.7, Plt 392; normal MCV and iron studies
• AST 30, ALT 23, T bili 0.2, albumin 2.8
• Hemoccult negative, stool WBC negative, spot fecal fat test
positive
• Celiac Panel
– IgA
69 (14-105)
– Endomysial AB
– Tissue Transglutaminase IgA AB
Positive
190.5* (>40)
What is Celiac Disease?
• Auto-immune condition
• Occurs in genetically susceptible individuals
• A unique autoimmune disorder because:
– Environmental trigger (gluten) and the
autoantigen (tissue-transglutaminase) are
known
– Elimination of the environmental trigger leads
to a complete resolution of the disease
– Permanent sensitivity to gluten
Why is it Important?
 If untreated it poses long-term adverse health
consequences including:
 Malabsorption
 Anemia
 Poor growth
 Osteopenia
 Intestinal lymphoma
 Nutritional Deficiencies
 Iron, zinc, calcium, Vitamin A, D, E, and K
Occurrence
 Healthy Population:
1:133
 First-Degree Relative
1:18 to 1:22
 Second-Degree Relative
1:24 to 1:39
 Incidence- Females more than males
Pathogenesis
• Genetic- multi-factorial, polygenic
– HLA DQ2 and DQ8 are most common, but, not the only
• Over 90% of patients with CD have the DQ2
• Not diagnostic, 40% of population is DQ2+
– We know it is genetic-familial clustering
•
•
•
•
10% risk in first degree relatives
HLA identical siblings-30%
Monozygotic twins 75%
Dizygotic twins-10%
The Celiac Iceberg
Symptomatic
Celiac Disease
Manifest
mucosal lesion
Silent Celiac
Disease
Latent Celiac Disease
Genetic susceptibility: - DQ2, DQ8
Positive serology
Normal
mucosa
Clinical Manifestations
 Gastrointestinal Symptoms (“Classic”)
 Chronic or recurrent diarrhea
 Abdominal distention
 Abdominal pain
 Vomiting
 Anorexia
 Failure to thrive or weight loss
 Constipation
 Irritability
“Classic” Celiac Disease
Non-Gastrointestinal Manifestations







Dermatitis Herpetiformis
Dental enamel hypoplasia
Osteopenia
Osteoporosis
Short Stature
Delayed Puberty
Infertility
 Elevated transaminases
 Arthritis
 Neurological
 Epilepsy
 Ataxia
 Neuropathy
 Dementia
 Iron Deficiency Anemia
Dermatitis Herpetiformis
 Erythematous macule >
urticarial papule > tense
vesicles
 Severe pruritus
 Symmetric distribution
 90% no GI symptoms
 75% villous atrophy
Abnormal Laboratory Findings in CD
Asymptomatic
 Treatment with a gluten-free diet is recommended for
asymptomatic children with proven intestinal changes
 Asymptomatic patients at risk of osteopenia/osteoporosis
 Screening in asymptomatic patients:
•
•
•
•
•
•
Type 1 diabetes
Selective IgA deficiency
Down syndrome
Turner syndrome
Williams syndrome
A first degree relative with CD
10-20%
5%
5%
5%
5%
10%
Serological Tests
Role of serological tests:
 Identify symptomatic individuals who need a biopsy
 Screening of asymptomatic “at risk” individuals
 Supportive evidence for the diagnosis
 Monitoring dietary compliance
Serum IgA Level
 IgA deficient individuals may have false
negative EMA-IgA & TTG-IgA
 Screen by checking total IgA level or including
an IgG based assay EMA-IgG and TTG-IgG)
 Approximately 6 % of Celiac Disease patients
have IgA deficiency
Antigliadin Antibodies
 Antibodies (IgG and IgA) to the gluten protein in
wheat, rye and barley
 Advantages
 Relatively cheap & easy to perform
 Improved sensitivity & specificity in young
children
 Disadvantages
 Poor sensitivity and specificity overall
Deamidated Gliadin Antibody
• Most recent antibody test available
• Antibody response to deamidated gliadin in patients with
Celiac Disease seems to be more intense than the antibody
response to native gluten (AGA).
• Recent studies have shown that anti-TTG still performs
better, and it is currently significantly less costly than antiDGP testing.
Tissue Transglutaminase – TTG
and Endomysial Antibody - EMA
• Typically the screening test of choice
• Advantages
– High sensitivity and specificity (human TTG)
• Disadvantages
– False negative in young children
– Operator dependent
– Cost
HLA Tests
 Potential role for DQ2/DQ8
Asymptomatic relatives
Trisomy 21, Turner & Williams syndrome
Type 1 diabetes
Diagnostic dilemmas
• TTG +, EMA -, Bx -, Symptoms +
Role of Endoscopy
• To obtain a small intestinal biopsy for histologic
analysis to establish the diagnosis of CD
Normal Appearing
Scalloping
Nodularity
Intestinal Histopathology
 Histologic abnormalities associated with CD are
characteristic, but not completely specific.
 Classically, small intestinal mucosal surface is flattened with
absence or marked blunting of intestinal villi
 Total absorptive surface area is greatly reduced
 There are typically an increased number of inflammatory cells
present in the lamina propria (plasma cells, CD4 cells)
Treatment
 Only treatment for Celiac
Disease is a gluten-free diet
(GFD)
 Strict, lifelong diet
 Avoid:
 Wheat
 Rye
 Barley
 Oats?
Why is Adherence Important?
• when children with symptomatic celiac disease
adhere to a GFD it results in resolution of GI
symptoms, improved growth in height and
weight, and normalization of hematological and
biochemical parameters
• Celiac disease is associated with an overall
increased risk of mortality in adults which is
primarily the result of GI malignancies. When
CD is diagnosed in childhood and GFD is
initiated, there appears to be no increased
cancer risk and reduced risk of other
autoimmune diseases
Summary
 Celiac Disease is a common, subtle enteropathy with
variable presentation.
 Active, appropriate screening is needed to avoid long-term
complications of untreated CD.
 Life long adherence to the diet is important
32
Case 2
 An 8 month old child presents with a history of poor growth
and a chronic cough
 He was initially breast-fed, but due to frequent vomiting and
loose bowel movements, he was changed to formula feeding,
despite trials of different types of formulas (soy,
hypoallergenic, etc.), his clinical course was remarkable for
bloating, diarrhea and failure to thrive.
 He developed a daily cough and some respiratory difficulty. At
the age of 5 months he was hospitalized for respiratory distress
and was diagnosed as having asthma
 He continued to have loose, large, greasy, foul-smelling stools
and failure to thrive
 He is small for his age
 HEENT exam is significant for bilateral otitis media
and mild nasal congestion
 Lungs with good aeration and mild wheezing and
crepitation
 Abdomen soft, non-tender, active bowel sounds
 Color and perfusion are good
 Sweat test: Weight 120 micrograms; 105 mmol/L (normal
<60)
 Deep throat culture after coughing induced by respiratory
therapy using a suction trap collection unit (specimen
treated by laboratory as a sputum culture): Klebsiella
pneumoniae
 AST 44 H (normal 0-37), ALT 49 H, (normal l0-40), Alk Phos
324 (normal 104-345)
 Cystic fibrosis mutation analysis (genetic testing): Positive
for one copy of Delta F508 and one copy of R1066C
Overview
• Cystic fibrosis = abnormal chloride transport
caused by mutations in the CF Transmembrane
Conductance Regulator Gene (CFTR)
• Results in abnormally thick mucous, and
secretions in lumens of the body
–
–
–
–
Lungs
Gut
Pancreas
Biliary tract
• Class I-III mutations (ie. delta F508 genotype)
typically more severe than Class IV-V mutations
Major GI Manifestations
 Intestinal: GERD; Meconium Ileus; Distal Intestinal
Obstruction syndrome (DIOS)
 Constipation, Intussusception
 Pancreatic: Pancreatic Insufficiency; Failure to
Thrive; Malabsorption of A, D, E, and K vitamins
 Chronic Pancreatitis, CF Related Diabetes
 Hepatobiliary: Cirrhosis, Cholelithiasis
 Steatosis, Portal Hypertension
Pancreas: Insufficiency
Pancreatic Exocrine Insufficiency
• Most common GI complication of CF (85%)
• Inadequate pancreatic enzymes = poor nutrient absorption
– Fat-soluble vitamin deficiency, steatorrhea, malnutrition
• Pancreatic duct obstruction causes acinar cells to replace with
adipose  fibrotic tissue
• Decreased amylase, lipase, colipase, phospholipase
– Increased production of salivary amylase, brush border amylase and
peptidase, and lingual lipase
– Allows adequate monosaccharide and amino acid absorption, and some
lipolysis
• Decreased bicarbonate
– Worsens enzyme deficiency; enzymes optimal in alkalotic environment
Pancreas: Insufficiency
• Symptoms: foul smelling, bulky, frequent stools
– Clinical symptoms with >90% exocrine function lost
• Diagnosis: fecal Elastase or 72hr Fecal Fat testing + clinical
observations
– Fecal Elastase: high sensitivity and specificity for severe PI;
performs less well for mild-moderate PI[6]
– 72hr Fecal Fat more onerous to perform
• Others: fecal chymotrypsin, fecal lipase, secretin
stimulated duodenal aspirate
Pancreas: Insufficiency
• Management
– Pancreatic Enzyme Replacement Therapy (PERT)
• Pancreatic extract with lipase:protease:amylase
• Optimally dissolves in alkaline duodenal fluid
– Dose: IU/kg or IU/ mL formula or breast-feed
– Dosing is guided by symptoms: diarrhea, bloating, gassiness,
foul smelling, greasy stools
– Assess for other causes of malabsorption if no response to
enzyme therapy
Pancreas: Insufficiency
• Complications
– Prolonged enzyme contact with mucosa may cause ulcers
– Excessive doses (>10,000U/kg/d) can cause fibrosing
colonopathy (inflammation, strictures)[7]
– Inadequate replacement may cause:
• Growth failure
• Fat soluble vitamin deficiencies (ADEK)
• Bone disease (calcium, magnesium, Vitamin D, K)
Pancreas: Pancreatitis
Pancreatitis
• 10% of CF patients  rare in insufficiency
• Defective pancreatic secretion causes recurrent pancreatitis 
decline in exocrine function
– 20% of patients with pancreatic sufficiency at 1st episode of
pancreatitis will go on to pancreatic insufficiency
• Rarely 1st presentation of CF
Pancreas: CFRD
CF Related Diabetes (CFRD)
• Exocrine pancreatic insufficiency can evolve to endocrine
pancreatic dysfunction
• Risk factors: age, pancreatic insufficiency, delta F508
homozygous genotype
• 25% by 20 years of age
• Insidious onset: poor weight gain/growth, delayed
puberty, decline in pulmonary function
Summary
• CF affects lumens throughout the body
• Pancreas:
– PI in 85%, high index of suspicion even if clinically asymptomatic
– Pancreatitis 10%, rarely in PI
– Endocrine pancreatic dysfunction common with age