50 Years of Progress Since Congenital Sucrase-Isomaltase Deficiency Recognition

F ifty-three years ago, Holzel discovered that the chronic diarrhea of 2 malnourished infants was caused by lactase deficiency (1). The next year, Weijers reported that an identical syndrome could be caused by sucrase and/or maltase deficiencies (2). These conclusions were based on clinical response to dietary elimination and oral sugar loads, resulting in inadequate blood glucose responses (3). Congenital sucrase-isomaltase deficiency (CSID) was at first characterized clinically as a subset of chronic diarrhea. There was onset of watery diarrhea, with low fecal pH and high excretion of lactic acid and low-molecular-weight fatty acids, when ingested food contained the sugar. Soon after the publication of these observations, Prader and Auricchio (Fig. 1) described 5 children between 10 months and 4 years old belonging to 3 different families who were affected by the same disease; the sucrose intolerance was the result of a deficiency of small intestinal sucrase activity (4,5). Diagnosis was based on dependency of the diarrhea on sucrose in the diet and the high fecal excretion of lactic acid when the diet contained sucrose, and on the results of an oral sucrose tolerance test (flat blood glucose response and production of acute diarrhea with acid stools that were enriched with sucrose and lactic acid). Glucose plus fructose tolerance tests, however, were normal (increase of blood glucose and no diarrhea). These patients with CSID also presented symptoms of intolerance to feeding of maltodextrins or starch, but the symptoms were of a milder degree than those after sucrose feeding and with intolerance mainly in the first year of life. The a-amylase activity in duodenal juice was found to be normal for age and tolerance for maltose feeding was normal. It was therefore supposed that starch and maltodextrin maldigestion resulted from a deficiency of isomaltase activity associated with the deficiency of sucrase activity. At that time it was not possible to measure disaccharidase activities in small intestinal biopsies. Isomaltose was unavailable in sufficient amounts for oral tolerance tests. Auricchio therefore tested the in vivo isomaltase activity by oral tolerance tests with disaccharides or oligosaccharides containing the same 1–6 a-glycosidic bond as isomaltose. The first experiments were done with peroral tolerance tests using palatinose (6-a-D-glycopyranoside-D-fructose), a bacterial transformation product of sucrose (5) and afterward, with a mixture of 1–6 a-oligosaccharides obtained by enzymatic hydrolysis of dextran, which contained enriched isomaltose and isomaltotriose (6). In contrast to normal subjects, the patients with CSID had little or no elevation of blood glucose after the test dose and promptly developed diarrhea with large amounts of palatinose or isomaltose in the stools, which had the characteristic high content of lactic acid and low pH. Results indicated that in these patients, sucrase and isomaltase activities were missing simultaneously: ‘‘the isomaltase deficiency seems to explain fully the symptoms these patients get on the ingestion of starch or dextrins since isomaltose represents the bond existing in the branch point of starch’’ (6). From the Children’s Nutrition Research Center, Baylor College of Medicine, Houston, Texas, and the yEuropean Laboratory for the Investigation of Food-Induced Diseases (ELFID), University of Naples ‘‘Federico II,’’ Naples, Italy. Address correspondence and reprint requests to Dr Buford L. Nichols Jr, Baylor College of Medicine, Emeritus Director of the Children’s Nutrition Research Center, 1100 Bates St, Houston, TX 77030-2600. B.L. N. has received honoraria from QOL Medical. S.A. reports no conflicts of interest. Copyright # 2012 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/01.mpg. 0000421400.50010. 2a FIGURE 1. Andrea Prader (1919–2001, left) with Salvatore Auricchio. A clinical conference at Kinderspital and UniversitätsKinderkliniken in Zürich, Switzerland, in the early 1960 s when CSID was first discovered and poor starch digestion in CSID first recognized. FIGURE 1. From left to right: back row, William Bryant, Justus Leibig, Mohammad Chegeni, Peter Zimmer, David Rose, Mark Gilger, Antone Opekun, Gale Borden, Christina Lecea; third row, Bruno Chumpitazi, Ronald Scott, William Treem, Sursum, Derick Cooper, Zihua Ao, Byung-Hoo Lee; second row, Amy Lin, Beth Mays, William Dupere, Susan Baker, Buford Nichols, Teresa Davis, Bruce Hamaker, Roberto Quezada-Calvillo, Steve Avery; front row, Kyra Jones, Marcia Chaudet, Hassan Naim, Mary Money-Waldman, Veda Nichols, Fatimata Cisse, Meric Simsek, Like Yan, Ann McMeans, Mary Slawson. 8th Starch Digestion Consortium Workshop JPGN Volume 55, Supplement 2, November 2012