MALABSORPTION SYNDROMES (CHRONIC DIARRHEA)

Malabsorption syndrome (MAS) is a heterogeneous group of acquired or congenital disorders characterized by impaired digestion and/or absorption of all or some of the ingested dietary nutrients.

Transient malabsorptive defects secondary to post- infective diarrhea-induced mucosal injury (persistent diarrhea) are excluded from this definition.

Etiopathogenesis: Proximal half of small intestine is the most important site for absorption of proximate principles, e.g. proteins, fats and carbohydrates, while water and electrolytes are absorbed throughout its length. Bile salts and vitamin B₁₂ are selectively absorbed at terminal ileum. Iron is mainly absorbed in duodenum and proximal jejunum.

Intraluminal digestion depends on exocrinal pan­creatic enzymes (lipase, trypsin, chymotrypsin and others) and bile-salts from liver. Two important intestinal enzymes from proximal intestinal mucosa-secretin and cholecystokinin, released in response to the arrival of food, provoke these exocrine secretions.

Digestion and absorption of ingested nutrients is a complex and continuous process (Ch 14.1), dependent on the adequacy of-(a) digestive enzymes, (b) absorptive gut surface and (c) specific transporter mechanisms and enzyme activity, necessary for absorption of nutrients. These functions are deranged in MAS (Table 14.21) with impaired absorption of one or more nutrients.

According to the type of absorptive defects, MAS may be broadly divided into two categories:

a. Generalized MAS involving defective assimilation of multiple nutrients, due to loss of intestinal surface, mucosal integrity or motility disorders.

b. Selective MAS, limited to malabsorption of only one or two nutrients, due to specific defects in absorption mechanisms or transport enzymes, e.g. fat malabsorption in biliary disorders, protein

TABLE 14.21: Causes of chronic diarrhea (MAS)

Generalized malabsorptive states

• Chronic non-specific (Toddler's) diarrhea

• Impaired intestinal mucosal integrity

- Infective: Post-enteritis, giardiasis, tuberculosis

- Allergic: Food allergy, celiac disease, T. sprue

- Inhammatory bowel diseases: Crohn disease, U. colitis

- Drugs: Methotrexate, neomycin

• Reduced absorptive surface

- Congenital short bowel syndrome

- Surgical resection of large bowel segment

• Motility disorders (bacterial overgrowth)

- Stagnant loop syndrome

- Sub-acute intestinal obstruction

- Irritable bowel syndrome

- Iatrogenic: Laxatives, cholestyramine, antibiotics

Selective malabsorptive states

• Intestinal enzyme defects

- Carbohydrates: Disaccharidase (lactase) deficiency

- Amino acid transport defects, e.g. Hartnup disease

- Fat: Abetalipoproteinemia

- Vitamin: Pernicious anemia, folate malabsorption

- Minerals: Chloride-loosing enteropathy, A. enteropathica

• Pancreatic disorders (fat and protein)

- Cystic fibrosis

- Chronic pancreatitis

- Isolated enzyme defects: Lipase, trypsinogen

• Hepatic disorders (fat and fat-soluble vitamins)

- Cholestatic disorders: Biliary atresia, gallstones

- Chronic liver disease

- Primary bile acid absorption defects

*U. Colitis: Ulcerative colitis,

A. enteropathica: Acrodermatitis enteropathica

malabsorption in amino acid transport defects, zinc malabsorption in acrodermatitis enteropathica, etc.

Diagnostic evaluation in MAS aims not only to identify possible etiology but also the extent of its effect on health, e.g. nutrient deficiencies.

• Clinical evaluation, with special reference to:

± Age of onset,

± Relationship with introduction of cow-milk, wheat, egg, etc. in diet

± Preceding history of acute/recurrent diarrhea, ± Aggravation on selected foods (allergic)

± Family history (enzyme defects, celiac disease) ± Past history of GIT surgery/disease/drugs

± Presence of abdominal pain, melena, vomiting, etc. ± Signs of selective nutrient deficiencies, e.g. edema.

• Stool characteristics

± Foul-smelling and bulky (fat-malabsorption) ± Large and watery (congenital channelopathies) ± Frothy, explosive diarrhea (carbohydrate mal­absorption).

Stools are generally large and pale with offensive odor in small bowel diarrhea, while small volume, often associated with blood and mucus in large bowel disorders.

• Malabsorption tests: Some important tests for malabsorption are as follows:

- Fat malabsorption is characterized by bulky-foul smelling stools with steatorrhoea, i.e. presence of fat globules visually or on microscopy after sudan-red staining. Quantitative estimation of total fat excretion over 72 hours on a controlled diet (gt;5 gm/day) is a sensitive indicator of fat malabsorption.

- Carbohydrate malabsorption is characterized by watery and frothy stools with acidic pH (lt;5.6) and positive Benedict test for reducing sugar. As sucrose is not a reducing sugar, stool sample should be hydrolyzed by hydrochloric acid before testing.

- Protein malabsorption cannot be assessed directly as proteins are normally present in stool, though most of them are derived from bacterial sources rather than dietary proteins. Low serum albumin levels and high spot stool 1-antitrypsin levels indicate protein-loosing enteropathy.

- D-xylose absorption test: D-xylose is a pentose sugar absorbed mainly in upper small intestines. A blood concentration of lt; 25 mg/dl of xylose after one hour of oral dose (14.5 gm/m²) indicated proximal bowel lesion.

- Positive Schilling test despite intrinsic factor supplementation, indicates terminal ileum disease, as vitamin B₁₂ is absorbed in distal bowel (Ch 19.4.2).

• Etiological investigations: Considering the diverse etiology, investigations in chronic diarrhea are recommended in a sequential manner (Table 14.22).

TABLE 14.22: Investigations in MAS

Step I. (Preliminary screening tests)

• Stool examination

- Gross for fat globules, blood and volume

- Microscopic for fat globules, ova and cysts

- Biochemical for pH, reducing sugar

- Cultures for common/opportunistic infections

• Blood examination

- CBC/PS for typing of anemia, acanthocytes

- S. proteins for hypoproteinemia

- Baseline electrolytes

• Radiological investigations

- Contrast barium studies

- USG abdomen

Step II. (Specific diagnostic tests)

• Quantitative 72-hour fat excretion for steatorrhoea

• Breath hydrogen test for lactose intolerance

• Stool electrolytes for Cl-loosing enteropathy

• Sweat chloride test for cystic fibrosis

• D-xylose absorption test for proximal bowel disease

• Schilling test for distal bowel disease

• Upper GIT endoscopy/small bowel biopsy

• Colono/sigmoidoscopy/biopsy Step III (Rarely warranted)

• Hormonal studies: VA peptides, gastrin, secretin, etc. Management of MAS depends on etiology, though general principles are same as for persistent diarrhea, including nutritional management.

Celiac disease (Gluten-sensitive enteropathy, nontropical sprue) is one of the commonest causes of chronic diarrhea and MAS in children above 2 years.

Etiologically, celiac disease is a T-cell mediated auto­immune inflammatory disorder, representing small­bowel hypersensitivity to gliadin fraction of gluten, i.e. primary wheat protein. Tissue Transglutaminase (tTG) is an enzyme present in intestinal epithelium, which deamidates gliadin to stimulate the immune system and initiate inflammatory process in celiac disease.

Genetic predisposition is well known as: (a) over 90% cases are positive for HLA-DQ2 or DQ8 haplotype, (b) similar family history is present in ~10% cases, (c) nearly 100% concordance in monozygotic twins, and (d) higher risk in some genetic disorders, e.g.

Clinically, these children present at ~6 months of age after introduction of wheat-products in complementary diet with: (a) chronic diarrhea as large, pale bulky stools, (b) recurrent vomiting, and (c) failure to thrive; with intermittent worsening of symptoms (Celiac crisis). Onset of diarrhea before introduction of wheat products is against the diagnosis of celiac disease.

On examination, abdominal distension, short stature and generalized wasting are consistent features, along with pedal edema due to hypoproteinemia and clubbing in severe cases. Extra-intestinal manifestations, specially refractory iron deficiency anemia, are common in older children. Silent disease may be present in first-degree relatives with asymptomatic histopathological changes. Diagnosis is confirmed on small bowel biopsy to demonstrate characteristic villous atrophy along with repeat biopsy 1-2 years after gluten withdrawal, to show normalization of histology.

However, quantitative serum anti-tissue transglutaminase IgA antibody (IgA-tTG) is the screening test of choice as per ESPGHAN 2020 guidelines with sensitivity and specificity of 91-100%. Diagnosis of celiac disease can be made without duodenal biopsy, if—(a) IgA-tTG titers are gt;10 times of upper normal limit, (b) anti-endomysial antibody is also positive, and (c) there is definite clinical response to gluten-free diet. Biopsy is necessary for diagnosis in absence of quantitative IgA-tTG values.

Treatment includes exclusion of gluten-containing cereals (wheat, rye, barley) from diet, which provides symptomatic relief in 2-4 weeks with resumption of weight gain. Wheat is the major source of gluten in diet and all wheat-based foods should be completely avoided in celiac disease, replacing them with rice or maize-based foods. A short course of steroids may be indicated during celiac crisis.

Tropical sprue is a disease of unknown etiology (probably hypersensitivity), with diffuse chronic inflammation of small intestines, seen in many tropical countries including India.

Clinically, these cases present with intermittent watery diarrhea/steatorrhea, severe anorexia, failure to thrive, multiple nutrient deficiencies and mild fever. Small bowel biopsy may be needed to exclude celiac disease and other causes of MAS. Most episodes respond well to antibiotics and folate/vitamin B₁₂ supplementation. Cow-milk protein allergy (CMPA) is common in developed countries (2-5%) and is being increasing recognized as an important cause of chronic diarrhea in under-five Indian children.

Etiologically, CMPA is more common in children with similar family history and top-feeing in early infancy. It may present as—(a) IgE-medicated allergic reaction with urticaria, vomiting and hypotension soon after the consumption of milk, or (b) delayed hypersensitivity reaction with long indolent course of intestinal malabsorption.

Clinically, CMPA presents with recurrent bloody or watery diarrhea on cow milk exposure, occasionally associated with GERD, hematemesis and severe anemia. Respiratory and skin allergies are present in ~30-50% cases. Diagnosis must be suspected in a case with family history and eosinophilia and confirmed by the challenge test, i.e. disappearance of symptoms on elimination of cow-milk from diet for 1-2 weeks, which reappear on re-exposure. Positive skin prick test and elevated IgE levels suggest IgE-mediated disease.

Treatment involves removal of all animal milk and milk-products from the diet, replaced by extensively hydrolyzed formula (EHF) or soya milk, though ~10% may have concomitant soy allergy.

Nearly, half of the children outgrow CMPA by 1 year and gt;95% by 5 years of age. Breastfeeding may be continued despite mild symptoms, though mother must be advised to avoid consuming milk/milk-products during lactation period. Micronutrient supplements are necessary and trial-introduction of milk feeds should be attempted after first year.

Food allergy, other than CMPA, are uncommon con­trary to popular belief and usually present with extra- intestinal rather than intestinal manifestations. All adverse reactions to foods are not allergies.

Commonly implicated allergens include egg, peanuts and food-additives, e.g. preservatives (sodium meta bisulfite) coloring agents (tartrazine) and flavouring agents (monosodium glutamate or Azinomoto).

Clinical spectrum of food allergy is extremely wide, including gastrointestinal, respiratory and cutaneous manifestations, including serious anaphylactic reactions.

TABLE 14.23: D/D Crohn disease vs ulcerative colitis

Diagnosis depends on—(a) appearance of symptoms after introduction of suspected food item in diet, (b) relief of symptoms after elimination of that item, and

(c) reappearance of symptoms on re-introduction in the diet (challenge test). However, challenge tests should be avoided in cases with severe allergic reactions. Skin-prick tests are unreliable to identify the causative food, unless substantiated by strong cause-effect relationship.

Management of food allergy includes—(a) symptomatic treatment of acute attacks, and (b) elimination of sus­pected food item from diet, but only if strong correlation has been established.

Inflammatory Bowel diseases (IBDs) includes two important intestinal diseases-Crohn disease (CD) and Ulcerative colitis (UC), both characterized by chronic mucosal inflammation with intermittent exacerbations and remissions (Table 14.23). Another ~10% cases cannot be classified in these two categories and are termed as Indeterminate colitis.

Early onset IBD in young children is generally consi­dered as a different phenotype than adult-onset disease, due to strong genetically attributable risk.

Incidence: Children and adolescents years account for ~25% of all IBDs with mean age of presentation as ~11-12 years.

Etiologically, IBDs represent inappropriate immune response to environmental factors in a genetically susceptible host as:

• Many causative genes have been identified for IBD, e.g. NOD2 and IBD5, and

• More than half of these cases have specific antibodies, e.g. anti-saccharomyces cerevisiae antibodies (ASCA) in CD and perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) in UC.

Pathologically, CD may involve any part of gut, including terminal ileum and upper colon (50-70%), upper GIT (30-40%) and perianal lesions (15-20%). In contrast, lesions in UC are usually limited to colon and rectum, sparing rest of the GIT.

Further, UC lesions are in continuity with each other, while those in CD have normal intervening mucosa (skip lesions).

Clinical manifestations of both IBDs usually begin in late adolescence, with a waxing and waning course of variable severity, as follows:

• Recurrent crampy abdominal pain with sticky dia­rrhea dominates in CD, while UC usually presents with recurrent dysentery and tenemus.

• Constitutional symptoms, e.g. fever, anemia, weight loss, easy fatiguability are present in both IBDs, though growth failure is more prominent in CD.

• Extra-intestinal manifestations are present in 20-30% of both IBDs, including arthritis, uveitis, aphthous ulcers, cholangitis, erythema nodosum, etc. Clubbing is common.

• Perianal lesions, e.g. fistula, abscess, tags, etc. and complications like subacute obstruction due strictures or deep seated abscesses are common in CD.

Diagnosis must be considered in any case with history of recurrent/persistent abdominal pain and/or dysentery/ sticky diarrhea, for gt;4 weeks. Inflammatory markers, e.g. ESR, CRP are usually elevated. Fecal Calprotectin level is a reliable screening test to differentiate IBD from functional abdominal pain.

Confirmation requires: (a) upper GI endoscopy with biopsy, (b) colonoscopy with ileal intubation and biopsy in all cases, with CT/MRI to assess the severity of IBD. Multiple biopsies are required from different sites for correct diagnosis. Important investigational differences between CD and UC are as follows:

• Endoscopy reveals deep, irregular ulcers with normal intervening mucosa (skip lesions) in CD and concentric diffuse colitis with acutely inflamed and friable mucosa in UC.

• Barium studies may show thick ileal folds with narro­wed lumen (string sign) and linear ulcers (cobblestone appearance) in CD and loss of haustral markings with thickening of mucosal folds (lead-pipe colon) in UC.

• Histopathology reveals transmural inflammation of all intestinal layers with non-caseating granuloma in CD and only mucosal involvement with cryptitis or crypt abscesses in UC.

Management includes: (a) treatment of acute attacks, and (b) maintenance of remissions, as follows.

Ulcerative colitis in acute phase is generally treated with a 5-Aminosalcylate (5-ASA) drug, e.g. Sulfasalazine (PO 50-75 mg/kg/day q8hr), though steroids, e.g. prednisolone (PO 1-2 mg/kg/day q24hr) are used in severe cases, till remission is achieved. Rare refractory cases require treatment of acute attack with monoclonal antibodies, e.g. infliximab or calcineurin inhibitors (Cyclosporine/Tacrolimus), under expert guidance.

Once remission is achieved, it may be maintained with long-term use of 5-ASA or immunomodulators, e.g. azathioprine or 6-mercaptopurine in cases with ASA intolerance or poor response. Rare cases need Infliximab for maintenance.

Surgery is indicated in selected cases of: (a) treatment failure or treatment dependence, or (b) toxic megacolon, with a two-step procedure of colectomy and pouch formation with ileostomy as the first step, followed by ileostomy closure.

Crohn disease in acute phase is treated with steroids, e.g. Prednisolone (PO 1-2 mg/kg/day q24hr) for 2-4 weeks followed by slow tapering over 8 weeks. Exclusive enteral nutrition (EEN) is the treatment of choice for only luminal CD, while metronidzaole and/or ciprofloxacin are used for perianal lesions. Monoclonal antibodies, e.g. Infliximab may be used in non-responsive cases.

Once achieved, remission may be maintained with immunomodulators, e.g. azathioprine, 6-mercaptopurine or methotrexate (with folic acid). Rare cases need Infliximab for maintenance.

Surgery is indicated in non-responsive localized CD resect areas with macroscopic disease, e.g. ileocolonic area with right hemicolectomy. Surgery is also needed for intestinal strictures, perforation, intra-abdominal abscesses and perianal fistula. However, recurrence is common.

Prognosis: Most IBDs respond well to medical treatment during initial attacks, though intermittent exacerbations are common. Toxic megacolon is the most important complication in acute stage. Some cases may develop colonic cancers after 10-15 years.

Abdominal tuberculosis or “Koch's abdomenquot; refers to tubercular involvement of intestines, peritoneum and mesenteric lymph nodes, excluding involvement of other abdominal organs, e.g. kidney, gonads and adrenals.

According to site of localization, it may be classified as peritoneal, nodal and intestinal (Table 14.24). Intestinal infection tends to localize at ileocaecal region due to relative stasis and large lymphoid tissue.

Pathogenesis: GIT tuberculosis is usually acquired hematogenously during intermittent bacteremia from a pulmonary focus, though abdominal lymph nodes may be involved via retrograde lymphatic spread from mediastinal nodes. Direct GIT infection, as seen in Bovine tuberculosis, is very rare in India.

TABLE 14.24: Types of abdominal tuberculosis

• Peritoneal

- Exudative peritonitis (TB ascites)

- Adhesive or plastic peritonitis

- Miliary peritonitis

• Nodal: Mesentric TB (T. mesenterica)

• Intestinal

- Hypertrophic ileocecal

- Ulcerative

Clinical presentation depends on the site and nature of lesions. Intestinal tuberculosis present with:

• Intermittent episodes of diarrhea/constipation, due to subacute obstruction,

• Abdominal pain and/or distension with typical doughy feel and presence of ascites,

• Constitutional features, e.g. low-grade fever, anorexia and weight loss.

Hepatomegaly, ascites and abdominal lump suggestive of mesenteric lymph nodes or ileocaecal mass may be present.

Complications, e.g. intestinal obstruction, fistula formation, peritoneal cold abscesses are common while perforation and hemorrhage is rare in intestinal disease.

Diagnosis usually rests on USG or contrast-enhanced CT (CECT) showing (a) concentric bowel thickening with contracted cecum, distorted ileocecal angle and short strictures in intestinal disease, (b) conglomerate lymph nodes of gt;1 cm with central necrosis in nodal disease, and (c) mesenteric thickening gt;15 mm with ascites in peritoneal disease. Rarely, focal granuloma may be present in liver or other organs. Barium meal with follow-through has been conventionally used for diagnosis of intestinal tuberculosis, though rarely used at present (Fig. 14.18).

Peritoneoscopy is highly sensitive and specific (gt;93% and 98% respectively) for diagnosis of peritoneal tuberculosis, showing hyperaemic and thickened peritoneum, whitish miliary nodules, adhesions and ascites.

All attempts should be made to confirm bacteriological diagnosis with drug sensitivity/resistance testing, from ascetic fluid or CT-guided peritoneal/node biopsy (Ch 10.13).

Fig. 14.18: Abdominal tuberculosis (barium follow-through).

Note pulled-up ileocecal region with strictures.

(Courtesy: Dr S Malik)

Treatment includes specific antitubercular therapy according to drug sensitivity profile along with suppor­tive treatment (Ch 10.13). Surgery is indicated in only in-(a) non-resolving intestinal obstruction, (b) perforation peritonitis, abscess or (c) fistulous communication, preferably after antitubercular therapy.

Toddler's diarrhea (chronic non-specific diarrhea) is the commonest and self-limiting cause of chronic diarrhea in infancy, with onset between 6 months and 3 years of age.

First morning stool is usually well formed but the frequency (4-6/ day) and liquidity increases as the day progresses, sometimes containing mucus and undigested food. Dehydration or failure to thrive is typically absent. Similar family history is common and symptoms may be precipitated by teething or common infectious illnesses. Excessive ingestion of fruit juices or non-absorbable sugars has been implicated in etiology.

Diagnosis involves exclusion of more serious causes. No specific treatment is required except dietary modi­fication (high-fibre, high-fat, low-carbohydrate diet). Problem resolves spontaneously by 3-4 years of age.

Other important but uncommon causes of MAS are as follows:

Chronic malnutrition is a common cause of MAS, due to—(a) intestinal villous atrophy, more prominent in Kwashiorkor, (b) bacterial overgrowth in upper intestine due to relative immunodeficiency, (c) suboptimal exocrinal pancreatic functions. Vitamin A supplements are beneficial to some extent in these cases.

Immunodeficiency disorders, congenital (SCID, IgA deficiency) or acquired (HIV, malignancy, iatrogenic) are emerging as important cause of chronic diarrhea and malabsorption, either due to primary disease or secondary infections. Giardiasis and rotaviral infections are common cause of chronic infective diarrhea in these cases, apart from opportunistic infections, e.g. Candida, Cryptosporidium, Isospora, CMV, Mycobacterium avium intracellulare, etc.

Chronic liver disease may lead to fat malabsorption due to impaired secretion of bile acid and bile salts in duodenum. Apart from primary disease, these cases present with steatorrhea and signs of fat-soluble vitamin deficiency, e.g. vitamin A (skin and ocular xerosis), vitamin E (progressive spinocerebellar degeneration with peripheral neuropathy), vitamin D (resistant rickets) and vitamin K (bleeding diathesis).

Pancreatic disorders: Cystic fibrosis is the commonest cause of malabsorption due to exocrinal pancreatic insufficiency, followed by Juvenile tropical pancreatitis (Ch 14.16). Shwachman-Diamond syndrome is a rare cause of pancreatic steatorrhea with failure to thrive and neutropenia or chemotaxis defects.

Cystic fibrosis is an autosomal recessive defect in salts and water secretion by epithelial cells, leading to desiccation of exocrinal secretions. While meconium ileus is the earliest presentation in ~ 10-20%, older cases present with steatorrhea, recurrent respiratory illnesses, salty-skin and other complications (Ch 16.10).

Structural intestinal defects are rare causes of MAS, commonest being Blind-loop syndrome and short bowel syndrome.

Blind loop syndrome denotes abnormal stasis of small intestinal contents, due to—(a) congenital malrotation, bands or diverticula, or (b) acquired postoperative adhesions or chronic inflammatory bowel disorders. Stasis allows bacterial overgrowth in upper small bowel, which deconjugate bile salts (fat malabsorption), cause brush border injury (disaccharide intolerance) and bind Vitamin B₁₂ to prevent its absorption. Clinicoradiological indicators of chronic intestinal obstruction are often absent. Oral metronidazole or non-absorbable antibiotics, e.g. neomycin or gentamycin, may be used for temporary control followed by operative correction.

Short bowel syndrome with loss of at least 50% of small bowel, may be congenital or postoperative. Resultant decrease in absorptive surface leads to fat and carbohydrate malabsorption. Management of these cases is a complex issue and involves total parenteral nutrition during acute phase, followed by gradual introduction of enteral feeding. Exposure to enteral nutrients facilitates compensatory growth of remaining bowel. Non-absorbable antimicrobials, anti-motility drugs and cholestyramine may be useful in select cases. Long-term prognosis is poor unless prolonged TPN is possible to allow gradual bowel growth. Many of these patients may ultimately require small intestinal transplant.

Specific absorption/transports defects for many nutrients are known, although rare. Some important ones include:

Abetalipoproteinemia is rare autosomal recessive deficiency of #946;-lipoproteins, essential for chylomicron formation. These cases present with: (a) failure to thrive and steatorrhea since early infancy, (b) neuroocular manifestations beyond first decade, (c) acanthocytosis in peripheral smear and (d) abnormal lipid profile, i.e. extremely low cholesterol, LDL and VLDL levels. Treatment involves replacement of long-chain fats with medium-chain triglycerides in the diet, which do not require chylomicrons for absorption, along with fat­soluble vitamin supplements in large doses (Ch 11.6.2).

Chloride-loosing enteropathy is a rare congenital defect in ileal chloride transport, presenting as severe watery diarrhea since birth with dehydration and unique pattern of dyselectrolytemia-hypokalemia with hypochloremic alkalosis. Diagnosis rests on stool electrolytes with chloride content exceeding sum of the sodium and potassium contents. Treatment is supportive.

Acrodermatitis enteropathica, an inherited defect of zinc malabsorption, presents with—(a) chronic diarrhea, (b) mucocutaneous lesions, and (c) failure to thrive. Oral zinc supplements (1-2 mg/kg/d) lead to rapid improvement. (Ch 6.9)

Amino-acid transport defects are rare malabsorption defects for select amino acids, important ones including: Cystinuria (no diarrhea) and Hartnup disease (Ch 11.6.1).

Glucose-galactose malabsorption is a rare autosomal recessive defect of glucose-galactose transport across the intestinal brush borders, which presents soon after initiation of breastfeeding with chronic diarrhea, abdominal distension and dyselectrolytemia. Strict dietary restriction of glucose-galactose with use of fruc- tose-containing formula feeds is essential for survival.

14.13