Clinical Aspects and Treatment of Congenital Sucrase-Isomaltase Deficiency


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Congenital sucrase-isomaltase deficiency (CSID) was first described by Weijers and colleagues in 1960 and has subsequently been defined as an inherited deficiency in the ability to hydrolyze sucrose, maltose, short 1–4 linked glucose oligomers, branched (1–6 linked) α-limit dextrins, and starch (1). Exposure to these nutrients provokes osmotic diarrhea with pain, bloating, and abdominal distention; rapid small bowel transit and malabsorption of other nutrients; excessive bacterial fermentation of malabsorbed carbohydrate with colonic gas production and acidification of the stools; and at times, chronic malnutrition and failure to thrive (2). After the sucrase-isomaltase (SI) gene was identified on chromosome 3 (3q25–26) and was cloned in 1992 by Chantret and colleagues, more than 25 mutations in the gene responsible for the synthesis of SI have been discovered (3–6). These mutations result in a variety of defects in the folding of the synthesized propeptide chain; the initial high mannose and then complex glycosylation; the sequential export from the endoplasmic reticulum to the Golgi apparatus, and eventually to the apical membrane; the anchoring of the N-terminal aspect of the isomaltase subunit in the enterocyte microvillus membrane; and the normal architecture of the sucrase and isomaltase catalytic sites, which are independent of each other and can be affected separately, leading to isolated deficiencies (5,6). The intracellular phenotypic heterogeneity is reflected in a range of enzymatic capability ranging from completely absent sucrase activity to low but present residual activity and from completely absent isomaltase activity to normal activity. Because SI is responsible for approximately 60% to 80% of the maltase activity in the brush border of the enterocyte, maltase activity is also significantly reduced in almost all cases.In addition to the degree of enzyme deficiency, the appearance of overt clinical manifestations of CSID is partially determined by the amount of sugar and starch being consumed. Approximately 60% of the total calories consumed in the average diet in the United States originate from carbohydrates, with 30% of carbohydrate calories deriving from sucrose (7). The typical adult consumes about 150 lb of sugar per year and 65 lb of sucrose. The influence of the dietary consumption of sucrose is best illustrated by the natural history of CSID in Greenland, where approximately 5% to 10% of Greenland Eskimos are affected (8). Before the introduction of a Western diet in the middle part of the last century provoked by the settlement of Greenland by northern Europeans from Denmark and other European countries, CSID was unknown among the indigenous population, who consumed a fish-and-marine mammal–based diet, relatively high in fat and protein and low in carbohydrates and sucrose. A marked increase in diarrhea and other gastrointestinal symptoms in the indigenous population led to studies in the 1970s that delineated the prevalence of CSID. The early introduction of sucrose and starch in the form of baby juices, baby food fruits and certain vegetables, and sucrose- and maltodextrin-containing infant formulas also plays a role in the timing of clinical manifestations of CSID.Other hormonal and dietary factors and micronutrients also influence small intestinal sucrase activity. Unlike lactase activity that is unresponsive to lactose consumption, sucrase activity is inducible by a high-sucrose, high-carbohydrate diet and reduced by a high-protein, low-carbohydrate diet (9). Both thyroxine and corticosteroids induce the expression of SI on the brush border of the enterocyte (10). In animal models, dietary-induced iron deficiency results in decreased small-bowel disaccharidase activity, with lactase affected more than SI (11). This appears to be the result of decreased gene expression caused by overexpression of PDX-1, a repressor of the lactase and sucrase promoter regions.

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