Initial recognition of the importance of disaccharide digestion in pediatrics is attributed to Howland (1), who in 1921 clearly described postinfectious carbohydrate intolerance and advocated the removal of carbohydrate from the diets of infants with prolonged diarrhea. Pediatricians followed his advice for many years with very little other than empiric evidence that it was correct. In 1959 Holzel et al. (2) reported siblings with severe congenital diarrhea and no elevation of blood glucose after lactose ingestion. The diarrhea resolved when the children were fed a lactose-free diet. This report of primary disaccharide intolerance led to the discovery of several types of familial carbohydrate-induced diarrhea. Two later reports established that intolerance to a specific disaccharide could cause postinfectious diarrhea. Haworth and Ford in 1960 (3) and van der Kamer and Weijer (4) in 1962 reported on patients with postinfectious diarrhea whose blood glucose failed to increase after disaccharide ingestion and who responded to removal of the disaccharide from the diet.
It was not until Dahlquist (5) published measurements of the disaccharidase activity in the mucosa of human small bowel in 1962 that studies of disaccharide intolerance focused on the sugar-splitting enzymes of the digestive tract. Miller and Crane (6) localized the activity to the brush border of the epithelial cell. Subsequently, individual disaccharidases were found in an array along the intestinal villus, with lactase being the most distal (7). Discovery of this ordered array led to the concept that lactase is the most vulnerable of the disaccharidases. It was hypothesized that if intestinal damage occurred, lactase would be most severely affected. The hypothesis was supported by several studies (8,9), but not by others (10,11).
Early attempts to define the normal disaccharide levels in humans of various ages were made by Townley et al. in 1965 (8), Welsh et al. in 1978 (12), and Lebenthal and Lee in 1980 (13). The most extensively used normal values are derived from Heitlinger et al. in 1991 (9). All these reports of normal values have been criticized because of small sample size, because of the inclusion of patients with diarrhea, or because a "normal" group of patients was not compared with an abnormal group.
The objective of the article appearing in this issue of the Journal of Pediatric Gastroenterology and Nutrition is to establish better normal values for small intestinal disaccharidase levels. Gupta et al. have identified a key problem with using presently accepted normals: what constitutes normal people? Heitlinger et al. (9) took the view that if the small bowel histology was normal, then the bowel has normal disaccharidase levels. This is clearly an oversimplification, in that, for instance, patients with sucrase-isomaltase deficiency can have normal histology. The authors of this article improve on this "normal" group by requiring that the biopsy specimen not only have normal histology, but also that the patient have no diarrhea. The study has attained a purer "normal" group, but it is still not a "true normal" group. The endoscopies and biopsies were performed for reasons that include conditions that could involve the small bowel, such as recurrent abdominal pain and failure to thrive. Characteristics of the normal group, not provided in this article, may influence the results, such as racial make-up. Additionally, the authors arbitrarily chose to divide their normal group by age into those less than 24 months and those greater than or equal to 24 months, They cite Heitlinger et al. (9) for justification. Indeed, Heitlinger et al. used 24 months as a cutoff age, not for physiologic reasons but rather because of the number of biopsy specimens available to analyze. In looking at the data of Heitlinger et al. it becomes clear that lactase activity begins decreasing in infants from 0 to 1 year of age and continues to decrease until they are 4 years of age. Therefore, although this article improves on defining what normal disaccharidase levels are, true normals are still elusive.
An interesting finding of this study is that lactase did not appear to be more vulnerable than other disaccharidases. A correlation between disaccharidase level and histologic damage occurred only when severe mucosal damage was present, but at that point all disaccharidase activity was decreased.
As clinicians ordering and interpreting tests daily, we are dependent on having normal values to make appropriate medical decisions. We are indebted to such investigators as Drs. Gupta, Chong, and Fitzgerald for questioning traditional normal values and providing us with better ones.
1. Howland J. Prolonged intolerance to carbohydrates. Arch Pediatr
2. Holzel A, Schwarz V, Sutcliffe KW. Defective lactose absorption causing malnutrition in infancy. Lancet
3. Haworth JC, Ford JD. Blood sugar in infants after lactose feeds. Lancet
4. Van der Kamer JH, Weijers HA, Dicke WK. Chronic diarrhea caused by a deficiency of sugar-splitting enzymes. Gastroenterologia (Basel)
5. Dahlquist A, The intestinal disaccharidases and disaccharide intolerance. Gastroenterology
6. Miller D, Crane RK. Localization of disaccharide hydrolysis in the isolated brush border portion of intestinal epithelial cells. Biochem Biophys Acta
7. Nordstroem C, Koldovsky O, Dahlquist A. Localization of β-galactosidases and acid phosphatase in the small intestinal wall: Comparison of adult and suckling rat. J Histochem Cytochem
8. Townley RRW, Khaw KT, Shwachman H. Quantitative assay of disaccharidase activities of small intestinal mucosal biopsy specimens in infancy and childhood. Pediatrics
9. Heitlinger LA, Rossi TM, Lee P-C, Lebenthal E. Human intestinal disaccharidase activities: Correlation with age, biopsy technique, and degree of villus atrophy. J Pediatr Gastroenterol Nutr
10. Calvin RT, Klish WJ, Nichols BL. Disaccharidase activities, jejunal morphology, and carbohydrate tolerance in children with chronic diarrhea. J Pediatr Gastroenterol Nutr
11. Harrison M, Walker-Smith JA. Reinvestigation of lactose intolerant children: Lack of correlation between continuing lactose intolerance and small intestinal morphology, disaccharidase activity and lactose tolerance test. Gut
12. Welsh JD, Poley JR, Bhatia M, Stevenson DE. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology
13. Lebenthal E, Lee P-C. Glucoamylase and disaccharidase activities in normal subjects and in patients with mucosal injury of the small intestine. J Pediatr
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