This document discusses disorders of malabsorption. It begins by defining malabsorption as diminished intestinal absorption of one or more nutrients that can result from defects in digestion or absorption. Malabsorption is then categorized as either generalized affecting multiple nutrients, or specific to certain nutrients. Signs, symptoms, diagnostic evaluations, specific conditions, treatments, and diet management are covered.

1. Dr. Janani D
Dr. Sheela Aglecha

2. ⦿Disorders of malabsorption are associatedwith
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.
⦿Categorization:
⦿Generalized mucosal abnormalities usually
resulting in malabsorption of multiple nutrients
⦿Malabsorption of specific nutrients

8. ⦿Diarrhoea
⦿Abdominal distension
⦿Failure to gain weight
⦿Fall in growth chart percentiles
⦿Appetite:
⦿Good + massive fecal loss no malnutrition
Eg: Exocrine pancreatic def.
⦿Reduced appetite + modest fecal loss  malnutrition
Eg: villous atrophy/ inflammation( CD, postinfectious
enteropathy

9. ⦿Onset: early infancy – congenital defect
⦿Onset: after introduction of particular food
provides diagnostic clues. Eg: sucrose in sucrose-
isomaltase deficiency
⦿Stool: watery & voluminous  secretory
diarrhorea due to CCD & MVID
⦿Explosive watery diarrhoea  carbohydrate
malabsorption
⦿Loose bulky stools  Crohn’s disease
⦿Pasty & yellowish offensive stools  exocrine
pancreatic deficieny
⦿Green stool with undigested peas &
carrotsrapid intestinal transit(self limiting)

10. ⦿Abdominal Distension
⦿Muscle wasting
⦿Disappearance of subcutaneous fat
⦿Loose skinfolds
⦿Older children- growth retardation

11. ⦿Edema- Protein losing enteropathy
⦿Clubbing- cystic fibrosis & CD
⦿Perianal excoriation & gaseous distension-
carbohydrate malabsorption
⦿Perianal & circumoral rash- acrodermatitis
enteropathica
⦿Abnormal hair- menkes syndrome
NUTRITIONALASSESSMENTS:
⦿ Vit D malabsorption: reduced bone mineral density
⦿Vit K malabsorption: coagulopathy
⦿PLE: Edema
⦿Iron malabsorption: Mchc anemia, low reticulocyte
count, low serum folate

12. ⦿Stool culture
⦿Stool ova & parasites
⦿Stool antibody tests for parasites
⦿Fecal leukocytes & Calprotectin or lactoferrin –
inflammatory disorders
⦿Stool pH & reducing substances – carbohydrate
malabsorption
⦿Stool osmolality – diff b/w osmotic & secretory
diarrhoea
⦿Quantitative stool fat examination- fat
malabsorption
⦿Fecal Stool elastase-1 – exocrine pancreatic
deficiency

13. ⦿Complete Blood Count:
⦿Neutropenia- Shwachman syndrome
⦿Lymphopenia – lymphangiectasia
⦿Peripheral smear – Microcytic anemia
⦿Acanthocytosis- abetalipoproteinemia
⦿Sr
. Ig A & Anti TG Ab – If CD suspected

14. ⦿Stool pH – Acidic
⦿Stool Reducing substance – 2+
⦿Breath Hydrogen test: to identify specific
carbohydrate
⦿Small Bowel mucosal biopsies :
⦿T
o measure mucosal disaccharidases
⦿Primary enzyme deficiencies- mucosal
morphology is normal
⦿Secondary disaccharidase deficiency – villous
atrophy

15. ⦿Quantitative detemination:
⦿Coefficient of
fat absorption
= (fat intake – fecal fat loss) x 100
fat intake
⦿Preterm – 65-75%
⦿Term - 90%
⦿Older child – >95%
⦿Acid steatocrit test
⦿BA levels in duodenal fluid aspirate
⦿Sr
. Vit A, D, E
⦿Prothrombin test – for Vit K

16. ⦿Hypoalbuminemia
⦿Stool α-1 AT deficiency
⦿INVESTIGATIONS FOR INTESTINAL MUCOSAL
DISORDERS:
⦿Histologic examination of small bowel
mucosal biopsies – PAS staining & electron
microscopy
⦿Mucosal biopsies for disaccharidases enzymes
⦿Duodenal aspirate – pancreatic enzyme
concentration

17. ⦿Sweat chloride test- Cystic fibrosis
⦿Fecal elastase -1 estimation:
⦿Sensitive test
⦿Disadvantage: differentiation between
primary & secondary pancreatic insufficiency
is difficult
⦿Serum trypsinogen concentration:
⦿Screening test
⦿In cystic fibrosis, the levels are elevated in
early life, then gradually fall.
⦿Useful for monitoring

18. ⦿Gold standard test: Direct analysis of
duodenal aspirate for volume, bicarbonate,
trypsin, lipase upon secretin,
pancreozymin/cholecystokinin stimulation
⦿Nitroblue tetrazolium + paraaminobenzoic
acid test & pancreolauryl test – measure
urine / breath concentration
⦿Lack specificity & rarely used

19. ⦿Immune mediated systemic disorder elicited
by gluten in wheat & relate prolamines from
rye & barley in genetically susceptible
individuals
⦿Characterised by gluten dependant clinical
manifestations, CD specific antibodies, HLA-
DQ2 or DQ8 haplotypes and enteropathy
⦿Genetics:
⦿Strongest association with HLA-DQ2.5(1 or 2
copies encoded by DQA1*05 & DQB1*02)
⦿HLA DQ 8

20. Immunodominant epitopes from gliadin
Resistant to intraluminal & mucosal digestion
Incomplete degradation products
(immunostimulatory & toxic effects)
IL-5 & Type 1 Interferon
Alter phenotype of dendritic cells
enhanced by TG2
Lamina propria T cell activation
IL-21 & IFN –γ
T-cell activation
Metalloprotinase &
Growth factors
Flat mucosa
IL-15
CD 94 & NKG2D
NK cells expression
Cell apoptosis
Villous atrophy

21. ⦿Common in children diagnosed within 2 yrs of
life
⦿Chronic diarrhoea
⦿Vomiting
⦿Abdominal distension
⦿Muscle wasting
⦿Failure to thrive
⦿Anorexia
⦿irritability

24. ⦿SYMPTOMATIC:
Frank malabsorption symptoms & signs
Extra-intestinal symptoms
⦿SILENT:
No apparent symptoms in spite of histological
evidence of villous atrophy; identified by serologic
screening in at risk groups
⦿LATENT:
Normal intestinal histology but at some other
time have shown gluten-dependant enteropathy
⦿POTENTIAL:
positive celiac disease serology but without
evidence of altered intestinal histology; may or may
not develop gluten dependant enteropathy later

34. ⦿Avoid all foods containing wheat, rye,
barley(pure oats is usually safe)
⦿Avoid malt unless clearly labelled as derived
from corn
⦿Use only rice, corn, maize, buckwheat,
millet, amaranth, quinoa, sorghum, potato,
soybean, tapioca, teff, bean, nut flours
⦿Wheat starch or products containing wheat
starch should only be used if they contain
<20ppm gluten & are marked gluten free

35. ⦿Read all labels & ingredients of processed
food
⦿Beware of gluten in medications,
supplements, food additives, emulsifiers or
stabilizers
⦿Limit milk & milk products initially if there is
evidence of lactose intolerance
⦿Avoid all beers, lagers, ales & stouts(unless
gluten free)
⦿Wine, most liqueurs, ciders, & spirits
including whiskey & brandy are allowed

36. ⦿ Beers, ales, other fermented beverages
⦿Bouillon & soups
⦿Candy
⦿Communion wafers
⦿Drink mixes
⦿Gravy & sauces
⦿Herbal tea
⦿Imitation meat & seafood
⦿Nutritional supplements
⦿Play doh
⦿Salad dressings & marinades
⦿Selfbasting turkeys
⦿Soy sauce

37. ⦿Threshold for gluten should be set to
<50mg/day, although individual variability
makes it difficult to set a universal threshold
⦿Compliance with a gluten-free diet can be
difficult. So, children should be monitored
with periodic visits for assessment of
symptoms, growth, physical examination,
complete blood count, thyroid diseases, &
adherence to gluten free diet.
⦿Periodic TG2 antibody levels – reduction in
antibody titres as indirect evidence of
adherence to gluten-free diet.

40. ⦿Includes 2 conditions characterised by typical
histological & ultrastructural lesions in
intestinal biopsies
⦿ Microvillous inclusion disease
⦿Congenital tufting enteropathy
⦿Tricho-hepato-enteric syndrome is also
usually classified in this group
⦿All the diseases in this category produces
secretory diarrhoea.

41. ⦿GENETICS:
⦿Autosomal recessive disease
⦿Mutations of MYO5B gene coding for motor
protein, myosin Vb, resulting in
mislocalization of apical proteins & disrupted
enterocyte polarisation.
⦿ t-SNARE syntaxin 3 mutation – milder
phenotype
⦿STX3 binding protein mutation causing
familial hemophagocytic lymphohistiocytosis
type5

42.  Diffuse thinning of mucosa
 Hypoplastic villous atrophy
 No inflammatory infiltrate
 Very thin/ absent brush border
 PAS & CD 10 positive apical
inclusions
Microvillus inclusion
Granules with microvilli
Lysosomes

43. ⦿Clinical features:
⦿At birth with secretory water diarrhoea upto
200-330ml/kg/day causing dehydration
⦿Failure to thrive
⦿Polyhydraminos in prenatal sonography
⦿T
reatment:
⦿No specific treatment
⦿Permanent parenteral nutrition
⦿Intestinal transplantation

44. ⦿Genetics:
⦿Epithelial Cell Adhesion Molecule(EPCAM)(does
not produce extradigestive symptoms)
⦿Hepatocyte Growth Factor Activator Inhibitor
type 2(SPINT2/HAI2)
⦿Clinical features:
⦿Intractable diarrhoea of infancy
⦿Extraintestinal: superficial punctate keratitis,
choanal atresia, esophageal/intestinal atresia,
anal imperforation, hair dysplasia, skin
hyperlaxity, bone abnormalities hexadactylia &
facial dysmorphism
⦿Histopathology:
⦿Teardrop shaped groups of closely packed
enterocytes with apical rounding of plasma
membrane

45. ⦿Genetics:
⦿TTC37 or SKIV2L
⦿Clinical Features:
⦿Early onset severe diarrhoea starting in 6 months
of life
⦿Facial dysmorphism, prominent forehead, broad
nose, hypertelorism, tricorrhexis nodosa
⦿Liver disease- in atleast half of patients; with
extensive fibrosis/ cirrhosis
⦿Histology:
⦿Nonspecific villous atrophy
⦿+/- mononuclear cell infiltration
⦿Without involving epithelium

47. ⦿Abnormal enteroendocrine cells development &
function
⦿C/F: Manifest with osmotic diarrhoea & in some
with other systemic endocrine abnormalities
⦿Treatment: nutritional support & hormonal
replacement
⦿Four genes are associated:
⦿NEUROG3
⦿RFX6
⦿ARX
⦿PCSK1

48. ⦿Associated with NEUROG3 mutation
⦿Clinical features:
⦿Generalised mucosal malabsorption, vomiting,
diarrhoea; oral alimentation with anything other
than water produces diarrhoea
⦿Dehydration
⦿Hyperchloremic metabolic acidosis
⦿FTT
⦿Biopsy: normal villus structure with complete
absence of secretory cell lineage with
preservation of goblet cells & paneth cells

49. ⦿Associated with RFX gene required for islet
cell development
⦿Clinical features:
⦿Chronic osmotic diarrhoea
⦿Other GI anomalies- annular pancreas,
malrotation, gall bladder agenesis
⦿Severe IUGR
⦿Neonatal diabetes
⦿Immunoflourescence staining:
⦿Pancreatic endocine cells are present but do
not express islet cell hormones

50. ⦿Associated with Arx gene
⦿Complex clinical phenotype of X-linked
intellectual disability, seizures, lissencephaly,
abnormal genitalia, congenital diarrhoea

51. ⦿Associated with PCSK1 gene
⦿Clinical features:
⦿Severe congenital chronic watery neonatal
onset diarrhoea
⦿Early- onset obesity
⦿Hyperinsulinism
⦿Hypoglycemia
⦿Hypogonadism
⦿hypoadrenalism
⦿Biopsy: Nonspecific enteropathy

53. ⦿Clinical features:
⦿Severe protracted diarrhoea of early onset,
not responding to dietary restriction
⦿Occur after first 6 months of life
⦿FTT
⦿Histology:
⦿Partial/ complete villous atrophy
⦿Crypt hyperplasia
⦿Chronic inflammatory cells in lamina propria
⦿Marled intraepithelial lyphocytosis
⦿Immunology:
⦿Anti-enterocyte antibodies
⦿Anti-autoimmune enteropathy-related 75 kDa
antigen

55. ⦿Apolipoprotein B(ApoB) and microsomal triglyceride
transfer protein (MTTP) act in concert to incorporate
triglyceride in chylomicron.
⦿ AR disorder of lipoprotein metabolism associated
with severe fat malabsorption /steatorrhea from
birth.
⦿Clinical features
FTT
Stool : pale ,foul smelling and bulky
Distended abdomen
Absent DTR due to peripheral neuropathy ( def of
Vit E)
Adolescence : Atypical retinitis pigmentosa ,
neurological symptoms.

56. ⦿Diagnosis
⦿Presence of acanthocytes in pheripheral blood
smear
⦿Extremely low level of blood cholesterol (<50 mg
/dl), very low TG (<20mg/dl), VLDL and
chylomicrons not detected.
⦿ Genetic study shows mutation in MTTP
.

59. ⦿Nutritional support and large supplements of
fat soluble vitamins A,D,E and K .
⦿Vitamin E (100-200 mg/kg/24 ) appears to
arrest neurologic and retinal degeneration.
⦿MCT can be used to supplement fat intake

60. ⦿AD inheritance
⦿Mutation in APOB gene , encoding ApoB .
⦿Parents of these patients have reduced
plasma LDL and apoprotein B concentration
where as parents of abetalipoproteinemia
have normal level.
⦿On electron microscopy of small bowel
biopies show many small vacuoles where as
in abetalipoproteinemia larger vacuoles are
seen.

61. ⦿ AR disorder
⦿Mutation in SAR1B gene which lead to defective
trafficking of necent chylomicron from ER to
golgi apparatus
⦿Clinical features steatorrhea, chronic diarrhea
and FTT
.
⦿Neurologic menifestatabion are less severe as
compared to abetalipoproteinemia.
⦿ Diagnosis plasma cholesterol level are
moderately reduced ( <75 mg/dl) and fasting TG
are normal.
⦿ Treatment same as abetalipoproteinemia.

62. ⦿Lipid storage disease due to mutation in LAL
gene ( lysosomal acid lipase ).
⦿Lal is enzyme that hydrolyzes cholestrol
esters and TG within endo lysosomes.
⦿There is lipid accumulation in multiple
organs including small intestine .
⦿Clinical features : vomiting, severe diarrhea
,hepatosplenomegaly , steatorrhea, liver
fibrosis, cirrhosis .

63. ⦿Insufficient free cholesterol available for
steroidogenesis in adrenal gland results in
adrenal insufficiency .
⦿A characteristic pattern of subcapsular
adrenal calcification represent a distinctive
marker of disease.
⦿Diagnosis : genetic
⦿T
reatment : Enzyme replacement

65. ⦿ Mutation in ABCA1 gene .
⦿ ABCA1 export pump helps in mobilisation of
cellular free cholesterol and phospholipid that is
converted in HDL.
⦿LOSS of function mutation leads to accumulation
of cholesterol in the intestine, spleen, tonsil,
relapsing neuropathy ,orange and brown spots in
colon and ileum and diarrhea.
⦿ Diagnosis : decreased plasma cholesterol level
ApoA I and A ıı , undetectable plasma HDL.
⦿Treatment : No specific therapy.

66. TANGIER DISEASE

67. ⦿ Approximately 95% of bile acids (BA) are reabsorbed
in terminal ileum and transported back to the liver
,enterohepatic circulation.
⦿Primary BA malabsorption : mutation in apical Na
dependent bile acid transporter.
⦿Secondary BA malabsorption : Ileal disease, ileal
resection
⦿ Clinical feature : diarrhea, steatorrhea ,and
reduced plasma cholesterol level.
⦿Diagnosis : reduced BA retention of radiolabeled 75
selenium –homocholic taurine acid taurine , increased
BA synthesis serum C4 , or increased fecal BA loss.
⦿Treatment : BA sequestrants eg cholestyramine,
colesevelam

68. ⦿Characterized by excessive enteric loss of
plasma protein.
⦿Impaired synthesis ( malnutrition,liver disese
), protein loss through other organ (kidney,
skin) or redistribution ( septic shock) have to
be excluded before considering PLE.
⦿Clinical presentation is variable and depends
upon underlying cause, but generally
includes edema and hypoproteinemia.

70. ⦿Diagnosis : typical clinical findings and
elevated fecal alpha 1 antitrypsin clearence
⦿T
reatment : supportive , low fat and high
protein diet ,MCTs.
treatment of underlying etiology.

72. ⦿The pathogenesis of diarrhea is not always
clear and may be related to persistent
infection or re-infection ,secondary lactase
deficiency ,food protein allergy, antibiotic
associated diarrhea or a combination of
these.
⦿Treatment: supportive, lactose free diet in
the presence of secondary lactase deficiency.

73. ⦿Excessive no. of bacterial in stomach and
proximal intestine alters gastric pH and small
bowel motility can result from disorders
such as partial bowel obstruction
,diverticula, intestinal failure,scleroderma
and PPI use.
⦿Prematurity
, immunodeficiency and
malnutrition are other causes.
⦿Diagnosis : > 10 5 CFU/ml in small bowel
aspirate or by lactulose hydrogen breath test
.
Measurement of D lactate.

74. ⦿T
reatment : Correction of underlying cause,
⦿Cycling of antibiotics including azithromycin
, trimethoprim -sulphamethoxazole ,
ciprofloxacin and metronidazole may be
required.
⦿Other non absorbable antibiotics such as
aminoglycosides, nitazoxanide , or
rifaxamine.

75. ⦿This is result of the interactions between
enteric pathogen ,enteropathy and
malnutrition and associated with peculiar
intestinal histology.
⦿The incidence is decreasing worldwide due to
improvement in hygiene and nutrition.
⦿Clinical feature : fever
, malaise followed by
diarrhea. After a week anorexia, intermittent
diarrhea and chronic malabsorption results in
severe malnutrition.

76. ⦿Diagnosis : small bowel biopsy shows villous
flattening with crypt hyperplasia and mild
intestinal inflammation,with lipid
accumulation in surface epithelium.

77. ⦿T
reatment : nutritional supplementation ,
including supplementation of folate and
vitamin B12 .
⦿ To prevent recurrence 6 month of therapy
with oral folic acid (5mg) and antibiotics are
recommended.

78. ⦿Chronic systemic disease caused by
Tropheryma whipple .
⦿Clinical features : diarrhea ,abdominal pain,
weight loss and joint pain. Malabsorption,
lymphadenopathy ,skin hyperpigmentation
and neurologic symptoms are also common.
⦿Diagnosis : P
AS positive macrophage in the
duodenal biopsy/ PCR

81. ⦿TREATMENT : a 2 week course of iv
ceftriaxone/ meropenem followed by
trimethoprim sulfamethoxazole for 1 year.

82. ⦿LACTASE DEFICIENCY :
a)Congenital lactase deficiency : rare,
symptoms occur on exposure to lactose in
milk.
b)Primary adult type hypolactasia : The
brush border lactase is expressed at low level
in fetal life and peaks from term to 3 year ,
after which gradually decreases with age.
c)Secondary lactase intolerance : follows
small bowel mucosal damage , usually
transient and improves with mucosal healing.

83. ⦿Diagnosis : H2 breath test ( 2g/kg up to 25kg)
⦿Treatment : lactose free diet. Live culture
yoghurt contains bacteria that produces
lactase enzyme and therefore well tolerated.

84. ⦿FRUCTOSE MALABSORPTION
Children consuming large quantity of fruit juice rich
in fructose, corn syrup presents with abdominal
distention , diarrhea and slow weight gain.
This is due to reduced presence of GULT 5 on
apical membrane of intestinal brush border
membrane.
Diagnosis Fructose H2 breath test.

85. SUCRASE ISOMALTASE DEFICIENCY
⦿AR
⦿Complete absence of sucrase and reduced maltase
digestive activity.
⦿ Clinical feature: Diarrhea, abdominal pain and
poor growth.
⦿ Diagnosis : Acid hydrolysis of stool for reducing
substance because sucrase is non reducing
substance.

86. ⦿Mutation in glucose galactose / Na co
transporter system
⦿Intermittent/ permanent glycosuria after
fasting or after glucose load is there as
transport defect is present in kidney also.
⦿Diagnosis : breath hydrogen test

87. ENTEROKINASE DEFICIENCY : Responsible for
activation of trypsinogen to trypsin.
TREHALASE DEFICIENCY : Trehalose is present
in mushroom and added to dry fruits.