disorders of carbohydrate absorption in childhood · by a young infant in milk feeds is large and...

J. clin. Path., 24, Suppl. (Roy. Coll. Path.), 5, 14-21

Disorders of carbohydrate absorption in childhoodCHARLOTTE M. ANDERSON

From the University ofBirmingham, Institute of Child Health, Francis Road, Birmingham

Until the last decade emphasis was placed on fatmalabsorption as the principal dietary cause ofpersistent diarrhoea in childhood. That abnormalitiesof the absorption of sugar could be responsible hadnot been widely realized and it is only 12 years sinceHolzel, Schwarz, and Sutcliffe (1959) in Manchesterdescribed familial congenital lactose intolerance;11 years since Weijers, van de Kamer, Mossel, andDicke (1960) described fermentative diarrhoea dueto dietary sucrose; and nine years since Anderson,Messer, Townley, Freeman, and Robinson (1962)gavethe first demonstrationthat thedisaccharidases-sucrase and isomaltase-were not present in thesmall-intestinal mucosa of two siblings who pre-sented with persistent watery diarrhoea whichdisappeared on withdrawing sucrose from the diet.However, now we recognize a wide variety ofprimaryand secondary types of sugar intolerance involvingboth disaccharides and monosaccharides and theseare outlined in Table I.

Disaccharides Monosaccharides

PrimarySucrase-isomaltase deficiency

Glucose-galactosemalabsorption(fructose tolerated)

rInfantLactase deficiency

LAdultSecondary

LactaseMucosal damage deficiency Disturbed transport

Deficiency of all sugarsof all disaccharidases

Table I Types ofsugar intolerance in childhood

A glance into the past is always salutary, and onperusing the paediatric literature of the earlier partof this century, amongst German publications oninfant feeding, one comes across a number ofreferences to diets which excluded certain sugars.John Howland, the first professor of paediatrics atJohns Hopkins University, Baltimore, choseGermany for his postgraduate experience, andperhaps this is why he became interested and aware

of the possibilities of abnormalities in the digestionand absorption of dietary sugars and gave a paperentitled 'Prolonged intolerance to carbohydrates' ashis presidential address to the American PaediatricSociety in 1921. In this talk he gives a remarkablyclear clinical description of the symptoms of sugarintolerance and malabsorption as we know themtoday. He also recognizes that there are primarytypes and others secondary to such disorders asgastroenteritis, and he realizes that in some babiesonly disaccharides give trouble but in others a moresevere intolerance involving all sugars, even mono-saccharides, can occur. He deduces that the symptomof watery diarrhoea is associated with the osmoticpull of the unabsorbed sugar, and sums up by statingthat little more will be known about these conditionsuntil methods have been evolved to demonstrate theenzymes in the small intestine that are responsiblefor digesting and absorbing sugars. In this predictionhe was entirely correct but probably did not thinkthat it would be about 40 years before knowledgeoutlined by the previous speaker (p. 10) would beavailable so that the types of disorder referred to inTable I can now be precisely identified.

Symptoms and Clinical Pattern of Sugar Intolerance

Sugars should be quickly absorbed in the upper smallintestine. However, if they are not absorbed andremain in the intestinal lumen osmotic diarrhoeawill result and the sugars are in part excreted un-changed in the faeces and in part undergo bacterialdegradation causing further fermentative diarrhoea.Thus the symptom of sugar malabsorption isdiarrhoea. The osmotic component of the diarrhoeadepends for its severity on the concentration andtherefore osmotic pressure of the unabsorbed sugarin the lumen. Fluid and electrolytes are drawn intothe gut, peristalsis is stimulated by distension, andwatery diarrhoea results. As a result of fermentationthe stools become acid, with a high concentration oflactic acid; they are passed with gas from furtherfermentation of lactic acid to CO2 and water. Thusthe stools are watery, acid, with a pH less than 5 5,irritating to the buttocks, frequent, and noisily

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Disorders of carbohydrate absorption in childhood

passed. In the absence of such stools, the diagnosiscannot be upheld in childhood. In small infants onemust take care to collect the stools on a non-absorbent napkin or they may be mistaken for urine.The diagnosis is suspected from the typical history

of persistent fluid fermentative stools and the factthat the onset is related either to the introduction of,or changes in, the type of sugar in the diet, or to thepresence of some other gastrointestinal illness. Thusthe clinical history of a suspected case must containa detailed dietary history, particularly in regard tosugars added to feeds, and a knowledge of the type ofcarbohydrate present in the various milk preparationsfed to infants. In the primary types symptoms willeither be present from birth, as in lactose intoleranceand glucose-galactose malabsorption, in sucraseisomaltase deficiency when the milk feeding containssucrose, or when mixed feeding is introduced.As a result of osmotic diarrhoea there is excess

fluid and electrolyte loss and therefore dehydrationmay supervene. Intestinal hurry may result inaccompanying steatorrhoea and further calorie loss,and the weight may remain stationary or go down.On the other hand a compensating high intake offluid and calories may balance the losses and theremay be little or no failure to thrive or constitutionalsymptoms. Fermentation usually causes gaseousdistension and borborygmi which sometimes leadto colicky abdominal pain-more noticeable in theolder child.The symptomatology of sugar intolerance varies

considerably with age. Diarrhoea is much moresevere in the young infant than in the toddler orolder child and especially in the adult in whom thesymptoms may be confined to abdominal discomfortor colicky pain and borborygmi. There are severalexplanations for this. First the load of sugar takenby a young infant in milk feeds is large and theosmotic component of diarrhoea therefore plays apredominant role. Older children will often have alower intake of carbohydrate as disaccharide ormonosaccharide and a higher intake as starch and,as a consequence, symptoms are mild and moredifficult to diagnose. In the adult there may be littleor no diarrhoea unless a challenging dose of theparticular sugar is taken. The offending sugars arenormally taken in relatively lesser loads and theadult colon appears to reabsorb fluid entering fromthe small bowel better than the infant colon.

Diagnosis of Sugar Intolerance

That diarrhoea may be due to malabsorption ofsugar can be demonstrated by several methods. Thesevary from simple bedside tests to more complexclinical and laboratory techniques.

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pH OF STOOLThis is a simple bedside procedure. A pH of below5 5 indicates fermentative diarrhoea and is areflection of the low molecular weight fatty acids,particularly lactic acid (Weijers, van de Kamer,Dicke, and Ijsseling, 1961).

DEMONSTRATION OF REDUCING SUBSTANCESIN THE STOOLThis can be done (a) by Clinitest (Kerry and Ander-son, 1964), (b) by chromatography, or (c) byestimating the total reducing substances.

It must be emphasized that the stool tested forreducing substances must include any fluid portion.It is valueless to test a portion of solid stool removedfrom a napkin into which the fluid has soaked. Itmust also be emphasized that the stool is eithertested freshly at the bedside, or quickly transportedto the laboratory where it should be frozen iftesting is to be delayed. Otherwise further fermen-tation will occur and reducing substances disappear.

It should also be realized that only reducingsugars can be shown up by Clinitest, and if thepresence of sucrose is suspected in the stool it shouldbe tested before and after hydrolysis with diluteHCl.Minor quantities of reducing substance (less than

200 mg %) are present in many normal stools.Therefore Clinitest should only be consideredsignificant if 0-5% or over. Chromatography is usefulfor demonstrating the individual sugars present inthe stool, but too sensitive for assessing clinicalsignificance. In clinical practice it is rarely necessaryto estimate total reducing substance.

DEMONSTRATION OF HIGH LACTIC ACID CON-

TENTIt is necessary to collect stools for 24 hours and eachstool should be frozen shortly after being passed. Thetest (Weijers et al, 1961) is arduous and slow andnow rarely used in clinical practice.

SUGAR LOADING TESTS

These can be followed (a) by rise in blood levelsor (b) by stimulation of diarrhoea so that stoolscontain excess reducing substances.By this means individual disaccharides or mono-

saccharides may be given as challenging doses. Manyfavour estimation of blood levels and consider thata rise of less than 30 mg % during two hoursindicates sugar malabsorption. In childhood bloodlevels are unreliable. The dose is often unpalatableto babies or infants and may lead to vomiting or

slowed stomach emptying. It may also evoke an

emotional response, leading to rise in blood sugarby production of adrenaline.

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Charlotte M. Anderson

A loading dose, or to be certain, two consecutivedoses, accompanied by careful observation andcollection of the stools for six to eight hours after-wards, will demonstrate the passage of a fluid stoolpositive for reducing substances if sugar intoleranceis present.

THERAPEUTIC EXCLUSION OF DISACCHARIDESAND/OR MONOSACCHARIDESComplete cessation of symptoms and disappearanceof reducing substances from the stools indicatesintolerance to that particular sugar and is seen inprimary sugar intolerance. Secondary types mayshow great reduction in diarrhoea and loss ofreducing substances but, as in coeliac disease, notcompletely normal stools.

DIRECT MICROCHEMICAL ASSAY OF DISAC-CHARIDASE ACTIVITIESThe assay is done on the small-intestinal mucosaobtained by peroral biopsy (Dahlqvist, 1964;Messer and Dahlqvist, 1966). This test is importantin the final diagnosis of primary sugar intolerancebut of lesser importance in secondary varieties.Specimens should be taken from the upper jejunumrather than from the duodenum, and with theexception of very low or negative disaccharidaselevels, the absolute values have less diagnosticimportance than have the ratios between the variousactivities, eg, a ratio of sucrase to lactase greaterthan 1.

It must be realized, especially in the secondarytypes, that one small biopsy is not necessarilyrepresentative of the whole small intestine and, forinstance, in coeliac disease the proximal intestine maybe more abnormal than the distal and the disac-charidase levels in a single biopsy in the upperjejunum may therefore be misleading. Low disac-charidase levels in one specimen are not importantin the absence of symptoms of sugar malabsorption.

BARIUM FOLLOW-THROUGH STUDIES OF THESMALL INTESTINEThe barium is mixed with individual sugars, andillustrates the dilution effect of osmotic diarrhoea(Laws and Neale, 1966). This test will no doubt bediscussed in the next contribution. Its reliability ininfancy is less and the extra radiation exposureunnecessary as simple stool tests as described willreveal similar information.

Classification

The specific disaccharidase enzyme deficiencies werethe first to be recognized as a cause of persistentdiarrhoea in children. The second cause to be

recognized was the entity of glucose-galactosemalabsorption. It was then realized that the disac-charidases and the mechanisms of transport ofmonosaccharides could be secondarily disturbed inmany small-intestinal diseases (Table II) butparticularly following gastroenteritis. Persistentdiarrhoea in gastroenteritis is probably one of thecommonest and most important clinical situationsin which symptoms of sugar malabsorption aremanifest. The primary disturbances are rare incomparison but important to identify because theycan be so readily treated. I shall now deal individuallywith the various types of sugar malabsorption.

Post-gastroenteritisProtein calorie malnutrition-kwashiorkorMarasmusCoeliac diseaseGiardia lambslia infestationUlcerative colitisAny other disorder of small-intestinal mucosa

PrematurityImmunological deficiency diseases

In small intfantsGastrostomyIleostomyColostomy

Intestinal anastomosis-particularly in neonatesResection

Table II Conditions exhibiting secondary disaccharidasedeficiencies

SUGAR MALABSORPTION DUE TO DISACCHARI-DASE DEFICIENCIES

Sucrase-isomaltase deficiencyThe first clinical description of malabsorption ofsucrose was that of Weijers et al (1960) and thenAuricchio, Prader, Murset, and Witt (1961) describedmalabsorption of sucrose and maltose, particularlyisomaltose. In 1962, Dr Messer, in my own depart-ment in Australia (Anderson et al, 1962), for the firsttime demonstrated by a qualitative chromatographicmethod the absence ofsucrase and isomaltase activityin intestinal mucosa obtained by peroral biopsyfrom a baby with symptoms of sucrose malabsorp-tion. Subsequently children and adults with thiscombined enzyme deficiency were reported from anumber of countries and the condition was shown tobe familial. Kerry and Townley (1966) investigatedfour families fully and demonstrated a recessivemode of inheritance; all parents and a proportionof siblings were found to have intestinal sucrase andisomaltase levels below the average found in thecontrol group. It was considered that the ratio oflactase to sucrase was a better indication of the

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Childr-eni

Maltase

~ 4SLcraseLactase

Ss Ss Ss Ss

Genotype

Fig. 1 A family with sucrase-isomaltese deficiency. Three patients are shown. The parents and one sibling recognizedas heterozygotes by inverse ratio ofsucrase to lactase; there were three normal sibs. Isomaltase results are notshown individually.

heterozygous state, ie, seven of eight parents hada lactase/sucrase ratio greater than 0-8. A repre-sentative family is indicated in Figure 1. Threechildren are affected: the parents and one of foursibs have levels of lactase higher than sucrase.

Sucrase-isomaltase deficiency is present at birthbut symptoms are not manifest until sucrose ispresent in the diet. If the infant is breast fed thebaby's diet does not include sucrose until mixedfeeding is introduced, although fruit juices maystimulate diarrhoea. Some artificial milks may havesucrose added to them and in that case diarrhoeamay be manifest from birth. Thus a detailed feedinghistory is essential and the simple therapeutic test ofchanging the diet to one that is sucrose-free shouldresult in prompt cessation of the diarrhoea.

Isomaltose is not consumed as such, but duringthe digestion of starch isomaltase is concerned inthe hydrolysis of maltotriose (Messer and Kerry,

1967). Although starch is usually well tolerated bythese patients some may have mild symptomsrelated to its ingestion.There is one rather strange feature of this com-

bined enzyme deficiency. Although from examinationof the intestinal mucosa its absence may appear tobe complete, the symptoms vary in degree fromindividual to individual. They are more severe in theyounger child than in the older one and certainlymore severe than in the adult. In fact, patients withno symptoms have been observed, the diagnosisbeing made in the course of family studies (Kerryand Townley, 1965).

In the young child the symptom is responsible forfluid and electrolyte loss which may be accompaniedby mild steatorrhoea from the intestinal hurry.Sometimes in an older child there may be only minorabdominal distension and failure to thrive togetherwith some increase in the daily number of stools.

Pareints

100

80H

60 F

40 -

0oSs Ss SS Ss s

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Charlotte M. Anderson

Treatment is simple and effective and the olderpatient learns to accommodate to his enzymedeficiency and calculate just how much sucrose canbe taken before troublesome symptoms occur.Usually it is only necessary to avoid sucrose orsucrose-containing foods and fruit only, althoughsome patients avoid a large intake of starch.

LACTOSE MALABSORPTION

Primary-congenital alactasiaIn 1959, Holzel et al first described congenitalmalabsorption of lactose in two sibs who had haddiarrhoea since birth and in whom the diarrhoeaceased when only lactose was removed from the diet.No enzyme estimations were available at that time.About nine other reports in children followed and insome of them the lactase levels were shown to bevery low in the small-intestinal mucosa, whilst otherdisaccharidases were relatively normal. However,there were no lengthy follow-up studies to showpermanence of the enzyme deficiency and at aboutthis time secondary lactase deficiency was beingrecognized in very young infants who had persistentdiarrhoea following acute gastroenteritis (Sunshineand Ketchmer, 1964; Burke, Kerry, and Anderson,1965). In the latter patients lactase levels were verylow, with either normal or moderately lowered levelsof the other disaccharidases, such as sucrase and theother maltases, but all returned to normal when thesmall-intestinal mucosa regenerated following theinitial damage from gastroenteritis. Until recentlythere was still some uncertainty that true primarylactase deficiency from birth had been demonstrated.However, Levin, Abraham, Burgess, and Wallis(1970) have encountered a breast-fed infant whofrom the third day of life developed a severe waterydiarrhoea which ceased abruptly when lactose wasomitted from feeds and returned promptly when itwas resumed and in whom lactase activity wasvirtually absent from the duodenal mucosa whilemaltase, isomaltase, and sucrase activities were quitenormal. Histological appearances were normal. Thechild was still intolerant of lactose at 21 yearsof age but was progressing normally on a lactose-free diet. A sibling had died earlier at 51 monthshaving had persistent diarrhoea since birth. Theliving child seems to fulfil all the criteria for atrue primary congenital lactase deficiency. Thecondition seems very rare but there is no doubtthat low lactase levels are common in the olderchild or adult, and the next paper will deal fullywith this type of deficiency so I shall not elaborateon it here. Such persons must have normal levelsin infancy as they do not show symptoms at thatstage.

Congenital lactose intoleranceIn 1958 an Italian worker, Durand, described apeculiar disorder in infants characterized by vomiting,diarrhoea, failure to thrive, and the urinary excretionof large amounts of lactose and sometimes sucrose.Durand (1964) considered at first that a deficiencyof lactase was the cause of this syndrome in whichthe outcome was often fatal. Some patients alsoshowed an aminoaciduria. Subsequent scatteredreports by others revealed that lactase levelswere normal in similar cases and diarrhoea wasnot of the severity or type seen in lactase de-ficiency. This syndrome remains somewhat of amystery, the very unusual feature being the urinaryexcretion of large quantities of lactose. Smallquantities of this and other disaccharides may befound in urine of well children or more frequently ofthose with coeliac disease or other disorders of thesmall-intestinal mucosa, but this is not of anyclinical significance.

Recently Berg, Dahlqvist, Lindberg, and vonStudnitz (1969) have suggested that in this type oflactose intolerance there is a defect localized to thegastric mucosa resulting in abnormal resorption oflactose (and apparently other disaccharides) in thestomach.

Secondary lactase deficiencyWhilst lactase is the most important disaccharidasefor the newborn animal and human it is also the onewhich reaches its full level latest in intrauterine life(Sunshine and Kretchmer, 1964) and the one that ispresent in lowest concentration in the normal small-intestinal mucosa. As the disaccharidases are brushborder enzymes they are readily diminished in anycondition in which there is loss of normal mucosalepithelial cells, and lactase, because of its low initiallevels and the large load of lactose taken by an infantin comparison with its size, is the one whose im-pairment is most frequently manifest as a clinicalsymptom. Few adults will consume 2 pints of milkper day but this is customarily imbibed by a babyaged 4 to 5 months, and often extra lactose is addedto the feeds.

Table II lists the numerous situations which maybe accompanied by symptoms of secondary lactasedeficiency, and, if the mucosal damage is sufficient, bysymptoms of sucrase deficiency as well. Starch ormaltose intolerance is rarely clinically manifest as asecondary problem as the maltases, being the disac-charidases of highest activity, usually persist insufficient quantity to cope with the starch andmaltose loads.

In our society the commonest type of secondarylactase deficiency follows gastroenteritis of any type.If the small-intestinal mucosa is slow to repair so

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that the histological appearance remains abnormal,diarrhoea may persist when normal feeds are

resumed after the initial restriction in the acutephase. The diarrhoea is recognized to be that ofsugar intolerance by its watery nature, its acid pH,and positive Clinitest. The institution of lactose-freemilkfeeds will bring about the cessation of symptomsand a subsequent weight gain. Sometimes alldisaccharides must be withdrawn. Premature babieshave lower lactase levels than full-term babies(Auricchio, Rubino, and Murset, (1965) and earlyfeeding of high calorie feeds, in which lactose mayhave been added to raise the calorie content, may

precipitate diarrhoea. Prematurity plus gastroentericinfection is a potent cause of persistent diarrhoeafrom secondary lactose malabsorption. In under-developed countries kwashiorkor and malnutritionare commonly accompanied by lactase deficiencywhich is probably secondarily induced by repeatedgastroenteric infections and poor nutrition (Bowie,Brinkman, and Hansen, 1965). Operations on thegastrointestinal tract in newborn or small infantsare often followed by persistent diarrhoea which maybe due to sugar intolerance. The infant who fails togain weight and has stools with a fluid contentcausing excoriation around a colostomy mayrespond dramatically to a lactose-free milk feed.Patients with ileostomy or gastrostomy may be sim-ilarly affected, and gut resection with anastomosisis commonly followed by temporary sugar mal-absorption and fluid diarrhoea (Burke and Anderson,1966).The abnormal mucosa obtained from the upper

jejunum of a patient with coeliac disease will alwaysshow low disaccharidase levels, but only a very fewpatients show symptoms of sugar malabsorptionas well as steatorrhoea. In a few patients thewithdrawal of milk as well as gluten may be tem-porarily necessary but this should not be done onevidence of low disaccharidases in the biopsy only.In fact the determination of these enzymes as a

routine in coeliac disease is not indicated.

MALABSORPTION OF MONOSACCHARIDES

The previous speaker has discussed something of thenormal absorption of monosaccharides. There is nodoubt that there are differences in the transportmechanisms of individual monosaccharides anduntil recently it was thought that although glucoseand galactose were absorbed 'actively', ie, against a

concentration gradient, fructose was not. Recentwork (Gracey, Burke, and Oshin, 1970) showsfructose also to be actively transported althoughcertainly not by the same carrier system. Thisdifference is manifest in the clinical situation where a

malabsorptive defect of only glucose and galactose

exists in certain patients-in others all three are

affected.

Primary congenital glucose-galactose malabsorptionIn 1962 two groups, the French workers (Laplane,Polonovski, Etienne, Debray, Lods, and Pissarro)and the Swedish workers (Lindquist and Meeuwisse)described infants in whom sugar diarrhoea occurredwhen feedings were first instituted after birth but inwhom hydrolysis of the disaccharides appearednormal. These infants could not absorb glucose or

galactose, but their diarrhoea ceased when fructosewas the only carbohydrate in their feeds. Thecondition was shown to be familial, and there was

some evidence that the transport defect was alsopresent in the kidney. Within the next few years

occasional families with this sugar transport defectwere reported from a number of countries. Table IIIshows the absorptive problem affecting all sugars

except fructose from a patient investigated by ourown group. Other workers have gone on to showby autoradiographic studies the defective uptake of

24-Hour Faecal Sugar and Faecal Lactic Acid following Loading Doseof the Individual Sugars

Sugar (7g Reducing Substances in Faeces Lactic AcidDose) (mg) in Faeces

Amount (g) Type

Lactose 3 9 Glucose and galactose 143Sucrose 1 5 Glucose: trace of fructose 320Maltose 3 9 Glucose 54Glucose 4-1 Glucose 42Galactose 2-6 Galactose 26Fructose Nil Nil 5

Table III A patient with glucose-galactose malabsorp-tion

glucose and galactose in the intestinal villi (Schneider,Kinter, and Stirling, 1966). This defect is an un-common one, but treatment is effective and growthnormal if all disaccharides containing glucose orgalactose are excluded from the diet, and replacedby fructose. It is necessary in infancy to feed a milkwhich does not contain lactose or sucrose and onesuch-known as galactomin 19 (Trufood) whichcontains fructose-is commercially available.Gradually small amounts of starch are tolerated and,as the child grows, small quantities of milk or othersubstances containing glucose and galactose may beeaten, again by equating the intake against theproduction of diarrhoea.As yet I know of no published account ofan infant

who developed fluid diarrhoea on ingesting fructose,although I have had a personal communicationregarding a suspicious case from Norway. Fructose

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20 Charlotte M. Anderson

intolerance due to abnormality of the metabolismof fructose within the liver is an entirely differentcondition, being due to a defect of hepatic fructose-1-phosphate splitting aldolase (Froesch, Wolf,Baitsch, Prader, and Labhart (1963).

Secondary monosaccharide malabsorptionIn 1966, Burke and Danks published the records ofseveral infants who suffered an acute gastro-enteric illness in the early weeks of life, sometimesbefore leaving the maternity hospital. The diarrhoeapersisted when normal feeds were resumed afterinitial restriction and the stools were numerous,fluid in consistency, and contained large amounts ofreducing substances. No sugar, not even fructose,could be fed without stimulating diarrhoea which waslife threatening. The condition gradually amelioratedand after weeks or months sugars could be tolerated.Recovery was usually complete. Others have sincereported similar patients (Harries and Francis, 1968)and these workers have elaborated a synthetic sugar-free milk feed containing all necessary additiveswhich can be given to such infants. Lifshitz, Coello-Ramirez, and Gutierrez-Topete (1970) have alsoshown complete monosaccharide malabsorption inassociation with malnutrition and gastroentericinfection in South America.

Gracey, Burke, and Anderson (1969) suggestedfrom their findings that the sugar intolerance was oneaffecting the transport mechanisms of all mono-saccharides and was associated with the presence ofan abnormally profuse intestinal flora together withdeconjugated bile salts in the upper small intestine.They coined the name 'contaminated small bowel'syndrome for this condition but offered no explana-tion for the presence of the flora, although theysuggested that a more detailed examination of theflora than they had done might reveal anaerobicorganisms that could be responsible for the deconju-gation of bile salts. Gracey, Burke, Oshin, Barker,and Glasgow (1971) have recently described ex-periments in vivo and in vitro in blind-loop ratswhich show that deconjugated bile salts and ananaerobic flora are both present in that situationand the transport of monosaccharides is impaired inthe gut proximal to the blind loop, in particular inthe loop itself and to a much lesser extent in theimmediately distal gut. Experiments in vitro with ratgut segments using the Semenza and Miihlhaupttechnique(1969) also demonstrated reversibleimpair-ment of arbutin (a non-metabolized glucose ana-logue) uptake when deconjugated bile salts werepresent in the incubation medium (Gracey, Burke,and Oshin, 1971). It still remains to confirm theassociation of flora and deconjugated bile salts inthe infant clinical situation of monosaccharide

malabsorption, a problem we are currently investi-gating.

Summary

It can thus be seen that digesting and absorbingmechanisms for sugar in the gut can be readily upset,and depending on exposure to dietary sugars andtheir load, osmotic diarrhoea will result. Whilstgenetically determined errors of development of bothdisaccharidase enzymes and of monosaccharidetransport mechanisms have been clearly delineated,there is also a wide range of secondary disturbancesbased both on destruction of the integrity of themucosal epithelial cells and their brush border butalso on alteration of conditions within the lumen ofthe gut. The secondary disturbances are of muchgreater frequency in clinical practice than theprimary disorders and their recognition and under-standing will lead to a decrease in morbidity andprolonged hospitalization and debility in manypatients, particularly following acute gastroenteritisor surgical operations on the gut, especially inthe newborn period. We have noted sugardiarrhoea following neonatal gut anastomosis,resection, colostomy, ileostomy, and even gastro-stomy (Burke and Anderson, 1966). This may varyfrom just disaccharide intolerance to completemonosaccharide intolerance. An understanding ofthe disturbances of the absorbing mechanisms ofsugar following gut surgery would be of assistancein the postoperative management of such patients.The development of the technique of peroral

intestinal mucosal biopsy has been of great value inthe understanding of the different types of sugarmalabsorption, particularly those of primary geneticorigin. However, the presence of sugar intolerancemay be easily diagnosed by simpler tests, andintestinal biopsy followed by estimation of mucosaldisaccharides is rarely necessary in the diagnosis andmanagement of secondary sugar intolerance.

References

Anderson, C. M., Messer, M., Townley, R. R. W., Freeman, M., andRobinson, M. J. (1962). Intestinal isomaltase deficiency inpatients with hereditary sucrose and starch intolerance. (Letter.)Lancet, 2, 556-557.

Auricchio, S., Prader, A., Murset, G., and Witt, G. (1961). Sac-charoseintoleranz. Durchfall infolge hereditaren Mangels anintestinaler Saccharaseaktivitat. Helv. paediat. Acta, 16, 483-505.

Auricchio, S., Rubino, A., and Murset, G. (1965). Intestinal glyco-sidase activities in the human embryo, fetus, and newborn.Pediatrics, 35, 944-954.

Berg, N. O., Dahlqvist, A., Lindberg, T., and Studnitz, W. von. (1969).Severe familial lactose intolerance-a gastrogen disorder?Acta paediat. scand., 58, 525-527.

Bowie, M. D., Brinkman, G. L., and Hansen, J. D. L. (1965). Ac-quired disaccharide intolerance in malnutrition. J. Pediat., 66,1083-1091.

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Burke, V., and Anderson, C. M. (1966). Sugar intolerance as a causeof protracted diarrhoea following surgery of the gastrointestinaltract in neonates. Aust. paediat. J., 2, 219-227.

Burke, V., and Danks, D. M. (1966). Monosaccharide malabsorptionin young infants. Lancet, 1, 1177-1180.

Burke, V., Kerry, K. R., and Anderson, C. M. (1965). The relation-ship of dietary lactose to refractory diarrhoea in infancy. Aust.paediat. J., 1, 147-160.

Dahlqvist, A. (1964). Method for assay of intestinal disaccharidases.Analyt. Biochem., 7, 18-25.

Durand, P. (1958). Lattosuria idiopatica in una paziente con diarreacronica ed acidosi. Minerva pediat., 10, 706-711.

Durand, P. (1964). Lactose intolerance. In Disorders Due to IntestinalDefective Carbohydrate Digestion and Absorption, edited byP. Durand, p. 105. Il Pensiero Scientifico, Rome.

Froesch, E. R., Wolf, H. P., Baitsch, H., Prader, A., and Labhart, A.(1963). Hereditary fructose intolerance. An inborn defect ofhepatic fructose-l-phosphate splitting aldolase. Amer. J. Med.,34, 151-167.

Gracey, M., Burke, V., and Anderson, C. M. (1969). Association ofmonosaccharide malabsorption with abnormal small-intestinalflora. Lancet, 2, 384-385.

Gracey, M., Burke, V. and Oshin, A. (1970). Intestinal transport offructose. (Letter.) Lancet, 2, 827-828.

Gracey, M., Burke, V., and Oshin, A. (1971). Reversible inhibition ofintestinal active sugar transport by deconjugated bile salts invitro. Biochim. biophys. Acta. (Amst.), 225, 308-314.

Gracey, M., Burke, V., Oshin, A., Barker, J., and Glasgow, E. (1971).Bacteria, bile salts and intestinal monosaccharide malabsorp-tion. Gut. (In the press.)

Harries, J. T., and Francis, D. E. M. (1968). Temporary monosac-charide intolerance. Acta paediat. scand., 57, 505-511.

Holzel, A., Schwarz, V., and Sutcliffe, K. W. (1959). Defective lactoseabsorption causing malnutrition in infancy. Lancet, 1, 1126-1128.

Howland, J. (1921). Prolonged intolerance to carbohydrates. Trans.Amer. pediat. Soc. (N. Y.) 38, 393-396.

Kerry, K. R., and Anderson, C. M. (1964). A ward test for sugar infaeces. Lancet, 1, 981-982.

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