Investigations by Prader et al first demonstrated in 1972 that patients with congenital sucrase-isomaltase deficiency (CSID) also have starch maldigestion (1). The presence of coexisting starch and sucrose intolerances creates problems in childhood dietary management and reduces the value of oral sacrosidase supplements. Confirmation of starch maldigestion at the mucosal level is difficult because there is no specific substrate for enzyme assays, and sucrase-isomaltase (SI) and maltase-glucoamylase contribute to both maltase and glucoamylase assay activities. These considerations led us to examine starch digestion in a series of children with CSID. The subjects were previously studied using a 13C-sucrose breath test, which correlated with biopsy sucrase activities (2). Here we report the study of these subjects and controls using 13C-starch as the breath test substrate. Based on the role of SI activities on in vitro starch digestion, our hypothesis was that all individuals with CSID would have reduced breath 13CO2 enrichments after a 13C-starch load.
Although a large dose of naturally enriched cane sugar had been used by others, Robayo et al used a small dose of universally enriched 13C-substrates believing that detection of deficiencies would be more precise if the normal subject tests were highly enriched and the enzymes and transporters were not overloaded (2). The authors recognized that children and adults have different rates of glucose oxidation; thus, they normalized the test substrate oxidation to that of dose-equivalent 13C-glucose oxidation. The digestion and oxidation of uniformly labeled 13C-sucrose/glucose in patients with CSID agreed with duodenal biopsy sucrase activity and was fully corrected by oral yeast sucrase supplements (2). Clinical reviews report that some patients with CSID may also have starch maldigestion (1,3). Our uniformly labeled 13C-starch/glucose breath test panel demonstrates that starch digestion is poor in all patients with CSID. Starch breath tests do not fully correlate with duodenal maltase activity because of the 4 mucosal enzyme activities that are involved in mucosal starch digestion. The universally poor starch digestion in patients with CSID, however, confirms the deficient biopsy sucrose- and maltase-enzyme activities (2) and confirms Auricchio and colleagues’ pioneering CSID starch digestion studies (1,3).
After obtaining institutional review board–approved informed consent, 10 patients with CSID were diagnosed by intestinal enzyme activity determinations (2). One additional sibling with CSID was added in the present study. The control groups of subjects were recruited from the Nutrition and Gastroenterology Service at Texas Children's Hospital. Six normal controls were patients evaluated for incidental illnesses and 6 clinical controls (ages 1–15 years) were patients who underwent endoscopy and biopsy because of symptoms of recurrent abdominal pain (RAP). All 12 had normal levels of mucosal enzymes measured according to the Dahlqvist method (4) with normal histology and had normal 13C-sucrose breath test results. The control groups of patients were participants in a parallel approved protocol (5,6).
13CO2 Breath Tests
The 13CO2 breath tests were performed during 3 separate days for the control group and during 4 separate days for the CSID group in our general clinical research center. After overnight fasting, a 2.5-L reference breath sample was collected as a baseline for comparison of enrichments with the timed postsubstrate breath samples, as previously described (2). The breath test results were recorded as total breath CO2 concentration expressed as glucose-ΔOB 13CO2, sucrose-ΔOB 13CO2, or starch-ΔOB 13CO2.
Eleven patients with CSID, 6 controls, and 6 patients with RAP were studied by oral challenge 13CO2 breath tests (Table 1). Clinical details are provided in reference 2. No patients had recently received antibiotics. The 13CO2 test substrate/13CO2 glucose (% coefficient of glucose oxidation, %CGO) was calculated for breath enrichments to adjust for individual differences. There were no clinical symptoms from the 13C-substrates administered. Controls defined a 13C-starch benchmark lower level as mean − 1 SD (91 − 25 = lower level of 65 %CGO). %CGO values 30 to 90 minutes were averaged. Controls and patients with RAP had normal sucrase and maltase biopsy activities, but those of patients with CSID were insufficient (Table 1). Patients with CSID had deficient (P = 0.000) and subjects with RAP had normal sucrose digestion (P = 0.560) by 13C-sucrose breath test. All P\patients with CSID had deficient 13C-starch digestion (19 ± 11 %CGO) and 8 of 9 subjects with RAP also had deficient values (31 ± 16 %CGO). The individual study subject 13C-sucrose and 13C-starch results are compared in Figure 1. Starch digestion in patients with CSID was less than that in patients withRAP (P = 0.000), and both had values below normal (CSID, P = 0.001) and (RAP, P = 0.003).
When Dahlqvist first reported identification of 4 different maltase activities in human small intestinal mucosa, he hypothesized that no clinical syndrome of maltase deficiency that paralleled the syndromes of lactase and sucrase deficiency would be found (7). During this workshop, Lin and Lee (unpublished data, 2012) showed that there is diversity and commonality among these mucosal activities and their 4 subunits. This is an affirmation of early studies of children with CSID (3). The reduction in heat-labile fraction of maltase (SI) accounts for nearly all of the residual maltase-glucoamylase activity in CSID (3). In hindsight, the clinical sucrose intolerance may have eclipsed the starch intolerance that was recognized by the earliest investigators as a reduction in heat-labile fraction of maltase activity in the sucrose-deficient mucosa of patients with CSID. Karnsakul et al (6) found a 28% frequency of low mucosal disaccharidase activities in children with RAP (then termed dyspepsia). The poor response to 13C-starch breath tests in the present subgroup of patients with RAP leads to the speculation that the solubilizing activities of luminal α-amylase may be reduced in this subgroup with normal mucosal maltase activities. The luminal α-amylase enzyme amplifies the activity of mucosal maltase activities manyfold by increasing starch solubility (8).
Leeds et al reported that pancreatic exocrine insufficiency could be detected in 6.1% of patients who fulfilled the Rome II criteria for diarrhea-dominant irritable bowel syndrome, and suggested that selected patients may benefit from pancreatic enzyme therapy to control symptoms (8). The pathophysiology of this apparent amylase insufficiency remains unclear and further work is under way.
1. Prader A, Auricchio S, Muerset G. Dΰrchfall infolge hereditären Mangels an intestinaler Saccharaseaktivität (Saccharoseintoleranz). Schweizerischen Mediz Wochenschr
2. Robayo-Torres CC, Opekun AR, Quezada-Calvillo R, et al. 13C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients. J Pediatr Gastroenterol Nutr
3. Auricchio S, Ciccimarra F, Moauro L, et al. Intraluminal and mucosal starch digestion in congenital deficiency of intestinal sucrase and isomaltase activities. Pediatr Res
4. Dahlqvist A. Assay of intestinal disaccharidases. Anal Biochem
5. Talley NJ, Stanghellini V, Heading RC, et al. Functional gastroduodenal disorders. In: Drossman DA, Corazziari E, Talley NJ, et al, eds. Rome II: The Functional Gastrointestinal Disorders. 2nd ed
. McLean, VA: Degnon Associates; 2000: 302.
6. Karnsakul W, Luginbuehl U, Hahn D, et al. Disaccharidase activities in dyspeptic children: biochemical and molecular investigations of maltase-glucoamylase activity. J Pediatr Gastroenterol Nutr
7. Dahlqvist A, Auricchio S, Semenza G, et al. Human intestinal disaccharidases and hereditary disaccharide intolerance. The hydrolysis of sucrose, isomaltose, palatinose (isomaltulose), and a 1,6-alpha-oligosaccharide (isomalto-oligosaccharide) preparation. J Clin Invest
Copyright 2012 by ESPGHAN and NASPGHAN
8. Leeds JS, Hopper AD, Sidhu R, et al. Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency. Clin Gastroenterol Hepatol