This retrospective study on disaccharidase activity in children and young adults suggests that certain GI symptoms could be associated with low disaccharidase activity. We found associations between low lactase activity and abdominal pain, and vice-versa. Abdominal pain was also found to be associated with lower palatinase activity. Although not statistically significant, low pandisaccharidase activity may be associated with a unique pattern of GI symptoms, higher frequency of abdominal pain and lower frequency of diarrhea, gastroesophageal reflux, and weight loss.
We found the association of low lactase activity alone in subjects with higher frequency of abdominal pain when compared to subjects with all normal disaccharidase activity, to be statistically significant (Table 3). This finding is similar to reports by others stating that in older children and teenagers, lactose intolerance is a common cause of abdominal pain [12, 21]. However, there are important differences between our study of low lactase activity and previous studies of lactose intolerance on GI symptoms. Lactose intolerance is a clinical syndrome diagnosed by adverse reactions due to ingestion of lactose; it is not necessarily related to low lactase activity level or having low lactase activity by our standards. In addition, we found upon comparison of subjects with any low disaccharidase activity to subjects with all normal disaccharidase activity, the frequency of abdominal pain was significantly higher in subjects with any low disaccharidase activity. This result, however, may have been skewed because children with low lactase activity alone made up 64% of the subjects with any low disaccharidase activity. Our finding that low lactase activity alone was the most common in our cohort is consistent with previous reports [13, 22].
Subjects with low pandisaccharidase activity may be correlated to higher frequency of abdominal pain (87.5%), but interestingly, lower frequency of diarrhea (12.5%), gastroesophageal reflux (12.5%), and weight loss (0%) compared to subjects with all normal disaccharidase activity (Table 3). This observation appeared to be unique, however, statistical significance was not achieved, likely due to inadequate sample size. A recent study found a moderately similar pattern to ours. In a study of 21 children with pandisaccharidase deficiency, Cohen et al. found that 95% had abdominal pain, 42% had diarrhea, and 38% had poor weight gain . We also believe that the discrepancy in the frequency of diarrhea and poor weight gain (included in weight loss for our study) could be due to the small sample size in our study. Additionally, we suspected that the frequencies of GI symptoms in subjects with only low lactase activity may be different from the frequencies in subjects low pandisaccharidase activity, but this also was not statistically significant.
Our findings strongly suggest that pediatric patients with abdominal pain present is associated with lower lactase activity compared to those with abdominal pain absent. This association had statistical significance (p < 0.001). There also appeared to be a relationship of the presence of abdominal pain with lower maltase, sucrase, and palatinase activity, but the reduction did not have statistical significance (Table 2). Because both sucrose and isomaltose are catalyzed by the same enzyme complex, sucrase-isomaltase, it may be expected that a reduction in palatinase activity would also correspond to a reduction in sucrase activity in the same person. However, sucrose and isomaltose are catalyzed at different active sites, located on different enzymes of the enzyme complex, which function independently of each other [23, 24]. This suggests that minor genetic mutations that alter the activity of one of the enzymes on the complex may not affect the other, or at least to the same degree . When the cohort was stratified by age group, differences in disaccharidase activity by GI symptoms were only present in the pre-teenage group suggesting that younger patients may be more sensitive to disaccharidase activity abnormalities or have not had time to adapt to living with reduced disaccharidase activity.
In our study, we found chronic duodenitis to be associated with having both low lactase and low alpha-glucosidases. Although it is known that cow’s milk allergy can cause duodenitis, lactase deficiency has not been reported to be associated with duodenitis . Wiecek et al. found decreased lactase activity in children with inflammatory bowel disease, however, they did not examine children without inflammatory bowel disease to see if the prevalence was different . In our study, we did not find any association with lactase alone, but with lactase in combination with other disaccharidase deficiencies which has not been examined before in relation to chronic duodenitis. This may suggest that chronic duodenitis may give different degrees of inflammation of entire the villous structure, affecting not only lactase on the tip, but alpha-glucosidases in the central structure of the villi. Because our study focuses mainly on the association of low disaccharidase activity to clinical symptoms in pediatric patients who had no villous atrophy, we do not claim that low disaccharidase activity is the cause of the GI symptoms experienced in our subjects.
In our study, there were a few limitations to consider. First, low activity of an enzyme is not equal to a clinical enzyme deficiency. Second, not all subjects had additional tests, such as hydrogen breath tests using lactose as a substrate, to confirm the reduction of a disaccharidase. Third, this was a cross-sectional study so there may have been some external factors, which affected a one-time result of activity of one disaccharidase or more, for example, transportation time which may artificially lower disaccharidase activity due to enzyme decomposition over time. However, because we made comparisons within our large group of subjects whose biopsy samples likely faced similar conditions, we believe that the effects of these mentioned limitations on our findings to be minimal. Since this is a retrospective study, we do not have clinical outcome data on restriction of corresponding disaccharides or polysaccharides such as lactose, sucrose, or starch. However, despite having been started 8 years ago, this study would be the largest of its kind .