Ethnic differences in intestinal disaccharidase values in children in Finland

BACKGROUND: Intestinal disaccharidase activities tend to be low in villous atrophy, but there are only a few reports of enzyme activities in children with normal villous architecture. METHODS: In the current study the data were reviewed on disaccharidase activities in duodenal biopsy specimens of normal villous structure in 223 children undergoing upper gastrointestinal endoscopy in 1997 and 1998. The ancestry was Finnish in 188 children (median age 8.0 years; range, 0.2-18 years), African in 27 children (median age 5.0 years; range, 1-13 years), and other in eight children. RESULTS: The mean activities of lactase, sucrase, and maltase were significantly higher in Finnish children than in children of African origin (P < 0.0001, P < 0.002, and P < 0.02, respectively). Lactase activity decreased with increasing age (P < 0.001), but age had no significant effect on maltase and sucrase activities. Among Finnish children, 31% (59/188) had lactase activity below the established reference range of 20 units (units are micromoles of substrate hydrolyzed per minute at 37 degrees C per gram of protein) and one child had a probable sucrase-isomaltase deficiency. When these 60 children with low enzyme activities were excluded, the geometric means were lactase, 35.7 units (95% confidence interval [CI], 32.8-38.6 units); maltase, 241 units (95% CI, 225-258 units); and sucrase, 57.5 units (95% CI, 53.5-61.6 units). Among the children of African origin, lactase activity was decreased in 67% (18/27). All three enzyme activities were decreased in parallel more often among the African children (8/27) than among the Finnish children (9/188; P < 0.002). CONCLUSIONS: Ethnicity has a strong effect on disaccharidase values in children with normal villous structure. African children have lower activities of lactase, sucrase, and maltase in duodenal specimens than do children of Finnish origin.     

Diamine oxidase and disaccharidase activities in small intestinal biopsies of children

A relationship between disaccharidase and diamine oxidase (DAO) activities was looked for by measuring these enzyme activities in histologically normal small intestinal biopsies of 18 children. The range for disaccharidase activities expressed in U g-1 wet weight was 0.1-5.7, 7.1-36.7, and 2.3-8.5 for lactase, maltase, and sucrase, respectively. The range for DAO activities expressed in nmol h-1 g-1 wet weight was 202-974. Significant correlations were found between disaccharidase and DAO activities (lactase versus DAO: n = 17, r = 0.80, P less than 0.001; maltase versus DAO: n = 18, r = 0.70, P less than 0.001; sucrase versus DAO: n = 18, r = 0.55, P less than 0.05). Our results further support the hypothesis that DAO is a marker of small intestinal functional integrity in children.     

Moderate and severe protein energy malnutrition in childhood: effects on jejunal mucosal morphology and disaccharidase activities

The enzymatic activities of maltase, sucrase, and lactase were determined in jejunal biopsies obtained from 24 children with gastrointestinal symptoms and different degrees of protein energy malnutrition (PEM) to see if these differences were related to the extent of malnutrition or concomitant small intestinal mucosal injury. Even in patients with moderate PEM, lactase activities were significantly lower than control values. The decrease in lactase activity seemed to depend on the severity of malnutrition. In contrast, maltase and sucrase activities were decreased only in second and third degrees of PEM, while no significant changes were observed in first degree and marasmic kwashiorkor. Histologically, all children with PEM had grade I to II mucosal injury which did not correlate with the degree of malnutrition. These results indicate that PEM affects each of the disaccharidases of the jejunal mucosa differently, with lactase being most sensitive to PEM and reflecting most closely the degree of PEM. In contrast, morphological changes showed no correlation with the degree of PEM.     

Disaccharidase activities in Belgian children: reference intervals and comparison with non-Belgian Caucasian children

Aim: To establish reference values for disaccharidase activities in Belgian children and to compare enzyme activities with those of non-Belgian Caucasian children. Methods: Data from Belgian children who had undergone endoscopic jejunal biopsies (1994-2000) for suspected malabsorption were reviewed. The patients were divided into three groups based on histology: (A) normal (n = 201), (B) moderate changes (n = 58) and (C) (sub)total atrophy (n = 14). The 95% reference limits for disaccharidase activities (U/g protein) were calculated for group A after exclusion of patients with a positive hydrogen breath test, a history of lactose intolerance or coeliac disease (final population: n = 151, 0.1-12 y). Values were compared with those of 34 non-Belgian Caucasian children with normal histology (28 of Mediterranean origin). Results: The reference limits (90% confidence interval) were 86 (65-111)-423 (366-494) for maltase, 9 (6-12)-91 (78-122) for lactase and 24 (18-30)-155 (120-184) for sucrase. No gender-related differences in enzyme activities were found. Lactase levels showed a slight decrease with increasing age. Disaccharidase activities of children with histologically confirmed mucosal injury were significantly lower than those of children with normal histology: median values for groups A, B and C were 208, 181 and 96, respectively, for maltase, 40, 28 and 7, respectively, for lactase and 69, 54 and 25, respectively, for sucrase. Median disaccharidase activities in biopsies with normal histology were lower in non-Belgian children, the difference being only statistically significant for lactase, 33 versus 40.

Conclusion: The reference values for Belgian children are well in line with other reported values from Caucasian children. Although enzyme activities are lower in children with histologically confirmed mucosal damage, they do not allow differentiation between histology groups. Lower lactase values were found in non-Belgian children.     

Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes

BACKGROUND: The relationship between symptoms, intestinal mucosal histology, and disaccharidase activities is not well defined. An analysis of disaccharidase activities was performed in children grouped by age, symptoms, and intestinal mucosal histology and normal values established. METHODS: Disaccharidase activities and histology of 246 endoscopically obtained duodenal biopsies in 232 patients (121 girls; age range, 0.08-17 years; mean, 5.9 years) in a 3-year period were reviewed. Patients were divided into two groups based on absence (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided by age into, less than 24 months of age and 24 months of age or more. Histologic changes within groups were classified as (A) normal, (B) mild, or (C) moderate to severe based on villus height abnormalities. A questionnaire was sent to 34 patients with hypolactasia to assess the efficacy of lactose avoidance and/or lactase supplementation. RESULTS: All group 1 patients had normal findings in analysis of mucosal specimens, and their disaccharidase activities showed normal values because they had no diarrhea. The geometric means (95% confidence interval) in children aged less than 24 months are (in micromoles of substrate hydrolyzed per minute at 37 degrees C per gram protein) (units [U]) lactase, 36.7 (13.4-100.4); maltase, 178.5 (88.9-356.3); palatinase, 12.7 (3.8-41.5); and sucrase 60.0 (24.0-148.1). In children 24 months of age or more, the values are 23.2 (3.9-108.1), 167.6 (78.8-355.9), 12.7 (4.9-32.9), and 51.0 (20.5-126.0), respectively. Only lactase activity decreased with age (p < 0.05). No differences in disaccharidase activities were noted in patients with and without diarrhea if the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea, values were commensurate with the degree of mucosal injury, especially in the older group. Twenty-two of 27 patients (81%) who responded to the questionnaire had benefited from lactase supplementation and/or lactose avoidance. CONCLUSIONS: We have established normal values for disaccharidase activities in the pediatric population. Although the disaccharidase activities correlate more with degree of intestinal mucosal injury than with symptoms, their activities are difficult to predict accurately based on these criteria. If required, disaccharidase activities should be measured biochemically.     

SUGAR ABSORPTION BY FLAT JEJUNAL MUCOSA

To obtain further information on the role of jejunal mucosa in malabsorption, characteristic activities of jejunal epithelial cells (disaccharid-ase activities and maltose and glucose absorption) were correlated with jejunal histology of 20 biopsy specimens with no villi (flat mucosa, F.M. (group I)) and 20 biopsy specimens with higher than 350 pm villi (control mucosa, C.M. (group 11). Except for lactase activity (F.M. = 13% of C.M.), the enzymatic and absorptive activities measured in F.M. specimens were uniformly about 30% of the corresponding activity in the C.M. tissue. An attempt was made to predict maltase and sucrase activities in F.M. specimens by extrapolating plots of C.M. activities vs. villous height. Measured enzyme activities in F.M. tissue, however, were significantly higher than the zero activity predicted by such plots. In contrast, the regression lines slopes of maltase or sucrase activities vs. total height (crypts and villi) measured in C.M. specimens were not different from the slopes obtained when data from C.M. and F.M. specimens were plotted together. These results suggest (i) the presence of absorptive cells in flat jejunal mucosa, which might be localised in so-called crypts; (ii) that a reduction in the number of epithelial cells is not the single mechanism in the origin of flat mucosa; (iii) lactase activity behaves differently than other studied epithelial activities.     

Intestinal disaccharidase and alkaline phosphatase activity in giardiasis

We report results on determinations of small intestinal brush-border enzyme activities in 22 children (aged 11 months to 14 years) with giardiasis. In particular, activities of disaccharidases (lactase, sucrase, maltase) and of alkaline phosphatase were investigated. Forty-one percent of the patients, irrespective of age, had a demonstrable depression of disaccharidase activities, usually in a combination involving two or more enzymes. A depression of intestinal alkaline phosphatase activity was present in 33% of patients, and only in those who demonstrated disaccharidase deficiencies. Mild villus atrophy was present in two mucosal specimens, whereas all others showed normal villus morphology by light microscopy. The results obtained in this study suggest that giardiasis in otherwise healthy children does not cause marked structural damage to the small bowel mucosa, as seen by the light microscope. However, some form of damage to the brush border does occur frequently, as evidenced by a depression of brush-border enzymes. This damage most likely contributes to the diarrhea and also to the carbohydrate intolerance in these patients.     

Cytopathic effects of measles virus on the human intestinal mucosa

We reported a case of measles with diarrhea in an infant. Capsule biopsy samples of intestinal mucosa taken 14 days after onset of fever was damaged and had low disaccharidase activities. Virus particles were found in the damaged villous cell. Second intestinal mucosa biopsy samples taken 28 days after onset of fever was found to be normal in structure, but lactase and sucrase activities were still low. Mucosal damage by virus particles was the cause of diarrhea in our infant.     

Glucoamylase and disaccharidase activities in normal subjects and in patients with mucosal injury of the small intestine

The development of glucoamylase activity was compared to that of disaccharidase in the small intestinal mucosa of infants and children. By the age of one month, infants have glucoamylase and disaccharidase levels comparable to those of young adults, indicating that young infants may be able to digest and absorb starches. In infants and children with varying degrees of mucosal injury of the small intestine, the activities of glucoamylase decreased progressively with increasing severity of the villus atrophy. However, the reduction of lactase, palatinase, and sucrase activities was more severe than the loss of activities of glucoamylase and maltase. Thus, children and infants may tolerate polymers of glucose better than disaccharides when they have mucosal injury associated with prolonged diarrhea.     

Human milk and the rate of small intestinal mucosal recovery in protracted diarrhea

STUDY OBJECTIVE: To determine whether human milk accelerates the recovery rate of injured small intestinal mucosa. DESIGN: Randomized, controlled trial. SETTING: County and nonprofit, private urban hospitals. PATIENTS: Moderately to severely malnourished infants less than 6 months of age who required parenteral nutrition for treatment of protracted diarrhea. INTERVENTIONS: Either a human milk preparation (n = 7) or sterile water (n = 9) was administered by continuous nasogastric feeding (14 mL/kg/d) over a 2-week study period while the infants received parenteral nutrition. MEASUREMENTS and MAIN RESULTS: Small intestine perfusion studies and biopsies were performed at the beginning and end of the study. Age, duration of prior illness, severity of malnutrition, glucose and water absorption, disaccharidase activities, atrophy of villi, and nutritional intake were comparable in both groups of infants. At the end of the 2-week study, improvement toward normal sucrase activity and intraepithelial lymphocytes was found in significantly fewer infants in the milk group than in the water group. No differences were noted in glucose and water absorption or in lactase and maltase activities as a function of the milk versus water treatment. CONCLUSIONS: Human milk did not accelerate functional recovery of the small intestinal mucosa.     

'Normal' disaccharidase levels in children

Results of disaccharidase assays in small bowel biopsies from 887 children over a 3 year period were analysed to establish normal values. Abnormal histology, the presence of giardia trophozoites or total absence of sucrase and isomaltase were found in 307 cases and these were excluded from further consideration. The results for maltase, sucrase and lactase from the remaining 580 children have been graphed as percentiles at various ages. They represent results which are as close to normal as it is possible ethically to obtain.     

'Normal'disaccharidase levels in children

Abstract Results of disaccharidase assays in small bowel biopsies from 887 children over a 3 year period were analysed to establish normal values. Abnormal histology, the presence of giardia trophozoites or total absence of sucrase and isomaltase were found in 307 cases and these were excluded from further consideration. The results for maltase, sucrase and lactase from the remaining 580 children have been graphed as percentiles at various ages. They represent results which are as close to normal as it is possible ethically to obtain.     

Disaccharidase and lysosomal enzyme activities in amniotic fluid, intestinal mucosa and meconium. Correlation between morphology and disaccharidase activities in human fetal small intestine.

Brush border membrane bound disaccharidases (sucrase and maltase) and lysosomal enzyme (alpha-glucosidase, beta-D-fucosidase and N-acetyl-beta-glucosaminidase) activities awere studied in amniotic fluid (AF). The above enzymes except N-acetyl-beta-glucosaminidase showed a decrease in activity with gestational age beginning at about the 19th week. The activities of sucrase and maltase correlate with the morphological maturation of fetal intestinal mucosa. The distribution of disaccharidases and lysosomal alpha-glucosidase in AF and intestinal mucosa showed different patterns suggesting that these enzymes originate in diverse fetal tissues.     

Disaccharidase activities in jejunal fluid.

Jejunal fluid and mucosal tissue were obtained simultaneously from the same jejunal site in a group of 29 children by a modified biopsy procedure. Lactase, maltase, and sucrase activities were measured in both fluid and mucosal specimens using the same analytical method. The fluid enzyme activities showed highly significant positive correlations with the same enzyme activity in the relevant tissue samples. Relative concentrations of disaccharidase enzymes represented by sucrase: lactase activity ratios also showed a highly significant positive correlation between fluid and tissue. This close relation suggests that the mucosa is the sole or predominant source of disaccharidase activity in the intestinal fluid. The results of kinetic studies comparing tissue and fluid enzyme characteristics also indicate a mucosal origin for the fluid enzyme activities. We conclude that disaccharidase activities in jejunal fluid reflect closely local tissue values and that these measurements may be useful in assessing mucosal enzyme activity in infants in whom jejunal biopsy is not possible.     

Intestinal enzyme profiles in normal and rotavirus-infected mice

To investigate further the pathophysiology of rotavirus-induced diarrhea, changes in specific activities of eight relevant intestinal enzymes [alkaline phosphatase, thymidine kinase, lactase, maltase, sucrase, Na+,K+-adenosine triphosphatase (ATPase), adenylate and guanylate cyclases] were measured following infection of suckling mice with murine rotavirus (epizootic diarrhea of infant mouse strain) and compared with age-matched control mice. The concentration of lactose within the lumen of the gastrointestinal tract during infection was also measured. During the course of infection, activities of alkaline phosphatase and lactase decreased, whilst the activity of thymidine kinase increased. Precocious maturation profiles of sucrase and maltase enzymes were observed. No significant changes were detected in the activities of Na+,K+-ATPase or the adenylate and guanylate cyclases. These results are discussed in relation to existing and novel hypotheses on the pathogenesis of rotavirus-induced diarrhea.     

Studies in meconium: disaccharidase activities in meconium from cystic fibrosis patients and controls.

Meconium ileus represents the earliest clinical manifestation of cystic fibrosis. The differences found in the composition and amount of protein, mucoprotein, mucopolysaccharides, and reducing sugars in meconium from newborns with cystic fibrosis might be of significance relative to the pathogenesis and early diagnosis of this disease. We studied the enzymatic activity of disaccharidases (lactase, sucrase, maltase, and palatinase) in meconium of infants with cystic fibrosis and controls. We found an increase in the specific activity of these enzymes in the meconium from infants with cystic fibrosis as compared to the specific activity in meconium from normal infants. The increase in the activities, expressed as micromols per gram of protein per minute was: lactase, 100 times higher; sucrase, 18 times; maltase, 4.8 times, and palatinase, 8.9 times.     

Congenital Lactose Malabsorption

A breastfed female infant is described who developed from the third day of life a severe watery diarrhoea, with weight loss. This ceased when lactose was omitted from the feeds and returned when it was resumed. Intolerance to this carbohydrate was confirmed by a lactose tolerance test which showed inability to hydrolyse the disaccharide. Absorption of glucose and sucrose was normal. No other cause for the diarrhoea was established. Congenital lactose malabsorption (alactasia) was confirmed by examination of the duodenal mucosa. The lactase activity was virtually absent, and the maltase, isomaltase, and sucrase activities were normal. The differential diagnosis of the congenital and acquired forms is discussed, and the importance of intestinal mucosal enzyme assays for final confirmation of the diagnosis is stressed.     

Disaccharidase activities in small intestine of rotavirus-infected suckling mice: a histochemical study

A histochemical study of the time course of the appearance and location of lactase and alpha-glucosidase (used to detect sucrase and maltase) activities was carried out on control and rotavirus-infected mice from 7 to 14 days old. The overall pattern of enzyme activity was in agreement with previous quantitative studies on the activities of these enzymes. No evidence was obtained to support the idea that lactase deficiency was the result of repopulation of villi (denuded of lactase-producing villus cells) with immature lactase-negative cells. Low lactase activity was more likely to reflect profound changes in metabolically crippled cells, and recovery of lactase activity with recovery of normal metabolic functions. The location of enzyme activity to brush border regions rather than the cytoplasm of villus enterocytes enhances the significance of previous quantitative studies on these enzymes. The timing and duration of diminished lactase activities were such that they were unlikely to cause the induction or perpetuation of diarrhea in murine rotavirus diarrhea. The appearance in infected animals of alpha-glucosidase 3 days earlier than normal indicates that, in addition to reversible changes seen with lactase, developmental changes were accelerated that affected both crypt and villus cells.     

Disaccharidase activities and intestinal absorption in infants with congenital intestinal obstruction

The results of studies on disaccharidase activities and on intestinal absorption in cases of complete and incomplete congenital small bowel obstruction are presented. Assays of the activities of maltase, isomaltase, sucrase, trehalase, and lactase have been performed on biopsy specimens taken at the time of surgery. In specimens taken from above the site of obstruction, the activities are reduced for all disaccharidases, and are particularly low for trehalase and lactase. There was no difference between the cases with complete and incomplete obstruction. Distal to a complete obstruction, trehalase and lactase were reduced, whereas in cases of incomplete obstruction, the activities of all disaccharidases were within what is considered normal in the reference material. Two months after surgery, the disaccharidase activities were found to be normal. One month after surgery, the absorption of glucose and vitamin A was markedly impaired in cases with complete obstruction, whereas that of D-xylose was not significantly reduced from normal. In cases with incomplete obstruction, the results did not differ from those found in normal infants. The fact that failure to thrive is common during the first months after birth in patients with congenital intestinal atresia, even when surgery is successful, may be explained by deficient intestinal absorption, particularly in patients with complete obstruction.     

Lactase insufficiency revisited

The definition of "insufficient" small bowel lactase activity varies greatly among authors. The present study is aimed at redefining lactase insufficiency by comparing intestinal lactase activity and results of the lactose breath hydrogen test. Primary "insufficient" lactase activity was considered to be present when a child with a normal small bowel histology showed lactose malabsorption as measured by the lactose breath hydrogen test. The lactase activity of 22 "normal" children ranged from 0.77 to 4.57 U/g wet weight, while five children showed primary lactase insufficiency as defined above. Small bowel lactase activity in the latter patients was less than 0.74 U/g wet weight. Sucrase and maltase activities were similar in both groups of patients. We conclude that children with a normal small bowel histology should be considered to have primary lactase insufficiency when small bowel lactase activity is below 0.75 U/g wet weight.