RARE DISEASE
Congenital sucrase-isomaltase deficiency
Congenital sucrase-isomaltase deficiency
Congenital sucrase-isomaltase deficiency
Synonyms: CSID, Congenital sucrose intolerance, Disaccharide intolerance
Synonyms: CSID, Congenital sucrose intolerance, Disaccharide intolerance
Synonyms: CSID, Congenital sucrose intolerance, Disaccharide intolerance
Drug discovery
2
drugs
With orphan designations
Overview
Congenital Sucrase-Isomaltase Deficiency (CSID) is a genetic disorder caused by mutations in the SI gene, leading to deficient sucrase-isomaltase enzyme activity. This results in malabsorption of sucrose and starch derivatives, manifesting as chronic diarrhea, abdominal pain, bloating, and failure to thrive in infants. Diagnosis requires endoscopic disaccharidase assays or genetic testing, though symptoms often overlap with irritable bowel syndrome (IBS), complicating identification [1][3][15][20].
Burden
Delayed diagnosis (often years) leads to growth impairment, malnutrition, and reduced quality of life [6][17].
Misdiagnosis as IBS or lactose intolerance is common, prolonging ineffective treatments [2][15][18].
Lifelong dietary vigilance is needed, with variable adherence and persistent symptoms in 25–40% despite therapy [17][18].
Therapies
Dietary modification: Restrict sucrose and starch (e.g., grains, potatoes); rice/corn starch may be tolerated after age 3–4 [15][18].
Enzyme replacement: Sacrosidase (Sucraid®) improves sucrose digestion but does not address starch malabsorption [3][13][19].
Multidisciplinary care: Requires collaboration with dietitians to manage nutritional deficits [8][17].
Categories: rare gastroenterological diseases, rare genetic diseases, rare inborn errors of metabolism
Research Papers
73 drug discovery papers about Congenital sucrase-isomaltase deficiency, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
73 drug discovery papers about Congenital sucrase-isomaltase deficiency, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-02-09 | A NOVEL HETEROZYGOUS SI GENE MUTATİON (C.1783G>T; P.G595X) İN A CHİLD WİTH CLİNİCAL FEATURES OF CONGENİTAL SUCRASE-ISOMALTASE DEFİCİENCY: A CASE REPORT
ABSTRACT Congenital sucrase–isomaltase deficiency (CSID) is increasingly recognized across a broad clinical spectrum, including milder presentations associated with heterozygous SI variants. Case: In this report, a child with chronic abdominal pain, bloating, frequent loose stools and recurrent perianal dermatitis is presented. Genetic testing identified a novel heterozygous nonsense SI variant, c.1783G>T (p.Gly595X). Cascade testing revealed the same variant in his father, who had intermittent loose stools, postprandial bloating, recurrent oral aphthae and IBS-like symptoms, suggesting a mild phenotype. Initiation of oral sacrosidase resulted in marked improvement in stool frequency, abdominal symptoms and perianal dermatitis. Conclusion: This case illustrates the clinical relevance of heterozygous SI variants and expands the mutational spectrum of CSID. The findings underscore the importance of considering SI-related carbohydrate malabsorption in children with chronic loose stools and functional gastrointestinal symptoms when routine investigations are unrevealing. KEYWORDS; Sucrase-isomaltase deficiency, SI gene, Carbohydrate malabsorption, Chronic diarrhea, Nonsense mutation, Sacrosidase therapy
2025-06-06 | Little Patients Big Discoveries: Potential Pediatric to Adult Neurogastroenterology Translation.
Pediatric neurogastroenterology conditions, including disorders of gut-brain interaction and motility disorders, affect millions of children worldwide. Owing to limited pediatric data, reference ranges and management are often extrapolated from adult studies. We review 4 pediatric neurogastroenterology areas where clinical science may translate and inform adult gastroenterology. Sucrase-isomaltase deficiency can be diagnosed through disaccharidase enzyme testing from duodenal mucosal biopsies. Dietary restriction and sacrosidase supplementation are effective, based on randomized controlled trials, in children with genetic sucrase-isomaltase deficiency; however, they remain to be rigorously studied in adults. Gastric emptying breath testing in large cohorts of children reinforces the importance of biological sex, puberty, and size while deriving normative reference values. Further study of gastric emptying breath testing in adults may help determine the influence of sex and hormones on gastric emptying rates, offering an opportunity to develop tailored reference ranges. Antegrade continence enema therapy is the most common reversible surgical treatment for children with chronic constipation, with high rates of efficacy. Few studies have investigated the efficacy of antegrade continence enema in adult populations. Auricular neurostimulation through percutaneous electrical nerve field stimulation is US Food and Drug Administration approved for use in adolescents with irritable bowel syndrome and functional dyspepsia based on sham-controlled, randomized trials with emerging efficacy data in other pediatric disorders of gut-brain interaction. To date, efficacy studies using auricular neurostimulation in adults with gastrointestinal disorders have not been performed. These areas highlight how pediatric neurogastroenterology generates discoveries with the potential to guide approaches in adult populations, underscoring the bidirectional value of translational clinical science.
2025-04-18 | Demystifying Carbohydrate Maldigestion: A Clinical Review.
Carbohydrate intolerance is a poorly understood and potentially overlooked cause of unexplained gastrointestinal symptoms, particularly among patients with disorders of gut-brain interaction. Symptoms related to carbohydrate intolerance arise from bacterial fermentation of unabsorbed carbohydrates leading to increased gases and osmotic load within the gastrointestinal tract. This mechanism is shared across various carbohydrates, including lactose, sucrose, maltose, fructose, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Primary forms of carbohydrate maldigestion typically affect one specific type of carbohydrate and result from inherited defects in specific brush-border enzymes or transport mechanisms, whereas secondary, or acquired, forms of carbohydrate maldigestion can arise from conditions that affect the structural integrity or function of the pancreas and small intestine. Although confirmation of a disaccharidase deficiency does not imply clinical relevance, obtaining a careful patient history with appropriate use of breath testing, duodenal disaccharidase assay, and response to dietary modification can help identify patients whose symptoms are associated with carbohydrate maldigestion and who may benefit from treatment. Dietary modification remains the cornerstone of therapy for patients with carbohydrate intolerance and should focus on determining the most liberal diet for patients that allows symptom control. Given the complexity and time-consuming nature of this process, clinicians are encouraged to engage the help of dietitians with expertise in the treatment of disorders of gut-brain interaction where available. Enzyme replacement therapy can also be an important adjunct to dietary management, with sacrosidase improving symptoms in sucrase-isomaltase deficiency and helping patients to liberalize their diet.
2025-04-12 | Invertase is an effective and cost-efficient alternative to sacrosidase oral solution for sucrase deficiency: a cohort study.
This study aims to evaluate the effectiveness of invertase as an alternative to sacrosidase solution for treating sucrase deficiency in paediatric patients and assess the prevalence of disaccharidase deficiencies in a tertiary care setting. A single-centre, retrospective study was conducted at the Royal Hospital for Children, Glasgow. Patients with low disaccharidase enzyme assay results, confirmed by duodenal biopsy and with normal duodenal histology, taken between 01 January 2011 and 31 August 2019, were included. Data collected included patient demographics, symptomatology, laboratory results and outcomes. The efficacy of invertase supplementation was assessed based on global clinician assessment and improvements in diarrhoea. An estimated treatment cost of invertase versus Sucraid (sacrosidase oral solution) is provided. Of 268 biopsy results from 245 patients, 38% showed low disaccharidase activity, with combinations of sucrase, maltase and lactase deficiencies observed in 19.4%, 25.0% and 29.9% of cases, respectively. Invertase was administered to nine patients with low sucrase. Following invertase treatment, 4/9 (44%) of patients experienced symptom resolution, 4/9 (44%) had a partial response and 1/9 (11%) had no response. Diarrhoea resolved or significantly improved in 8/9 (89%) of patients. The cost of invertase treatment was significantly lower than sacrosidase oral solution, with an estimated yearly cost of £1972 compared with £51 938 for sacrosidase oral solution. Invertase is an effective and cost-efficient alternative to sacrosidase for treating sucrase deficiency in paediatric patients. The study highlights the need for further prospective research to establish the prevalence of disaccharidase deficiencies and to optimise treatment strategies.
2024-12-10 | Frequency of Congenital Sucrase-Isomaltase Deficiency by Whole Exome Sequencing: Is It Really Rare?
Aim: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disease with a mutation in the sucrase-isomaltase (SI) gene and disaccharide maldigestion. With limited data, the estimated incidence of this disease is 57.59/10⁶ births and its heterozygosity rate is 1/132. We aimed to evaluate cases who underwent whole exome sequencing (WES) analysis in the medical genetics unit with regards to the frequency and clinic of CSID. Materials and Methods: The patients’ files who underwent WES between 2018-2023 were evaluated retrospectively. The demographic characteristics, complaints, physical examination, and laboratory findings of those patients with SI gene mutations were recorded. Cases with mutations were recontacted and symptom questioning was performed. Results: Mutations were detected in 25 (8.3%) of 300 patients who underwent WES analysis. One case had a compound heterozygous mutation, while 24 cases were heterozygous. The mean age was 22.4±17.6 years (1.8-52 years) and 16 (64%) were females. Nine of the cases (36%) were symptomatic. Conclusion: Data on the frequency of CSID are insufficient and variable in the literature. The SI heterozygosity rate in our study was higher than some studies. There were similar rates when compared to the study conducted on symptomatic pediatric patients in our country. Although the data of our study includes a heterogeneous group to evaluate the frequency of CSID, it consists of a group with suspected genetic diseases rather than healthy individuals. Therefore, large-scale population-based studies are needed.
small molecules
2026-04-18 | Dietary effect on glucose homeostasis is modulated by a loss-of-function variant in the sucrase-isomaltase gene: a randomised, dietary crossover intervention in Inuit.
Homozygous carriers of a loss-of-function variant in the sucrase-isomaltase (SI) gene (c.273_274delAG) are unable to digest sucrose and parts of starch. The variant is common only in Indigenous Arctic populations such as the Greenlandic Inuit and has been associated with a healthier metabolic profile. In a unique gene-diet intervention, we aimed to study whether the SI genotype modulates the effect of two different diets on glucose homeostasis and lipids. A genotype-based randomised crossover trial was conducted in homozygous SI carriers and non-carriers in Nuuk and Maniitsoq (Greenland), with two 3 day interventions and a 7 day wash-out period. Participants were ≥18 years, had no gastrointestinal disorders, diabetes nor carried an Inuit-specific high-risk type 2 diabetes variant in TBC1D4. The interventions were as follows: a Greenlandic fish- and meat-rich diet; and an isoenergetic Western diet with 11% energy from sucrose. The order of the diets was randomised by the participants using a dice and participants and personnel were not blinded. The primary outcome was glucose variability measured as CV. Fasting blood samples were drawn before and after each intervention for measurement of lipids, insulin and C-reactive protein. We assessed genotype × diet interaction effects using linear mixed models. The study was reported in accordance with the CONSORT 2010 statement: extension to randomised crossover trials and the consolidated criteria for strengthening reporting of health research involving Indigenous peoples (the CONSIDER statement). Seventeen carriers and 16 non-carriers completed the intervention. CV was higher on the Western diet than on the Greenlandic diet for non-carriers (β=5.23% [95% CI 3.02, 7.45]) but not for the carriers (β 1.27% [-0.86, 3.4]). Carriers had a 20% lower CV on the Western diet compared with non-carriers (pgenotype×diet=0.015). Carriers had lower fasting insulin levels than non-carriers at baseline, and the Greenlandic diet decreased the levels in non-carriers by 22.7 pmol/l (95% CI 5.1, 40.3) but not in carriers (pgenotype×diet=0.009). We observed no SI × diet interaction effects on lipids levels. Homozygous loss-of-function SI carriers show better glycaemic management than non-carriers on a Western diet, suggesting SI inhibition as a potential treatment target. ClinicalTrials.gov NCT05375656 FUNDING: Independent Research Fund Denmark, Greenland Research Council and Brugseni.
2025-07-30 | The Hypoglycaemic Effects of the New Zealand Pine Bark Extract on Sucrose Uptake and Glycaemic Responses in Healthy Adults-A Single-Blind, Randomised, Placebo-Controlled, Crossover Trial.
The New Zealand pine bark has been demonstrated in vitro to inhibit digestive enzymes involved in carbohydrate digestion (alpha-amylase, alpha-glucosidase, and dipeptidyl-peptidase 4 (DPP-4)). This study aims to investigate the inhibitory effects of the New Zealand pine bark on sucrose uptake and glycaemic responses in humans. A single-blind, randomised, placebo-controlled, crossover trial was carried out involving healthy adults (n = 40 (M: 12, F: 28), 30.1 ± 1.3 years, BMI 23.4 ± 0.5 kg/m2, HbA1c 32.5 ± 0.6 mmol/mol, FBG 4.7 ± 0.1 mmol/L). A control (75 g of sucrose powder only), and two doses of the pine bark extract (50 and 400 mg) were provided on separate occasions, with 75 g of sucrose mixed in 250 mL of water. Blood samples were collected at -10, 0, 15, 30, 45, 60, 90, and 120 min via a finger prick test. A linear mixed model for repeated measures (SPSS v30, IBM) was applied, and data presented as model-adjusted mean ± SEM. Compared to control (247.5 ± 14.0 mmol/L⋅min), the iAUCglucose was significantly reduced with the 400 mg dose (211.8 ± 13.9 mmol/L⋅min, 14.4% reduction, and p = 0.037), but not with 50 mg dose (220.8 ± 14.2 mmol/L⋅min, 10.8% reduction, and p = 0.184). Compared to control (9.1 ± 0.2 mmol/L), glucose peak value was significantly reduced with the 50 mg dose (8.6 ± 0.2 mmol/L, 5.5% reduction, and p = 0.016) but not with the 400 mg dose (8.7 ± 0.2 mmol/L, 4.4% reduction, and p = 0.093). There were no statistically significant changes in postprandial insulin levels with the pine bark extract compared to control. The New Zealand pine bark extract attenuated sucrose uptake with improved glycaemic responses, and may therefore be useful as a hypoglycaemic adjunct to the diet.
2024-01-07 | Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose
Sucrose is a disaccharide that is degraded into fructose and glucose in the small intestine. High-sucrose and high-fructose diets have been reported, using two-dimensional imaging, to alter the intestinal morphology and the expression of genes associated with sugar transport, such as sodium glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5). However, it remains unclear how high-fructose and high-sucrose diets affect the expression of sugar transporters and the intestinal morphology in the whole intestine. We investigate the influence of a chronic high-sucrose diet on the expression of the genes associated with sugar transport as well as its effects on the intestinal morphology using 3D imaging. High sucrose was found to increase GLUT2 and GLUT5 mRNA levels without significant changes in the intestinal morphology using 3D imaging. On the other hand, the delay in sucrose absorption by an α-glucosidase inhibitor significantly improved the intestinal morphology and the expression levels of SGLT1, GLUT2, and GLUT5 mRNA in the distal small intestine to levels similar to those in the proximal small intestine, thereby improving glycemic control after both glucose and sucrose loading. These results reveal the effects of chronic high-sugar exposure on glucose absorption and changes in the intestinal morphology.
2023-12-13 | Tune in to the terrific applications of turanose
Abstract Turanose, a rare sugar with low calorific value and glycemic index, used as an alternative to sucrose and other artificial sweeteners. The occurrence of turanose is in limited quantities, especially found in honey. Thus, it should be produced by either chemical or biological means. Turanose is released as a by-product during synthesis of the linear α -(1,4)-glucan from sucrose by the action of amylosucrase. In recent times, turanose attracted interest in several industries such as agricultural, food, and pharmaceuticals due to its feasible production. Hence, this review outlines about the history of turanose, its physiochemical properties, production along with inhibition and inducing effects. It is high time to tune in the terrific applications of turanose, as it retains the potential for more than a century of discovery, since 1889. These applications include detection of pathogens, facilitation of cellular respiration, regulation of inflammation, authentication of honey, phagodeterrency effects, osmoprotection, stabilization of therapeutical proteins, and edibility enhancement of foods.
2023-03-01 | Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives
Genetic variants causing loss of sucrase-isomaltase (SI) function result in malabsorption of sucrose and starch components and the condition congenital sucrase-isomaltase deficiency (CSID). The identified genetic variants causing CSID are very rare in all surveyed populations around the globe, except the Arctic-specific c.273_274delAG loss-of-function (LoF) variant, which is common in the Greenlandic Inuit and other Arctic populations. In these populations, it is, therefore, possible to study people with loss of SI function in an unbiased way to elucidate the physiological function of SI, and investigate both short-term and long-term health effects of reduced small intestinal digestion of sucrose and starch. Importantly, a recent study of the LoF variant in Greenlanders reported that adult homozygous carriers have a markedly healthier metabolic profile. These findings indicate that SI inhibition could potentially improve metabolic health also in individuals not carrying the LoF variant, which is of great interest considering the massive number of individuals with obesity and type 2 diabetes worldwide. Therefore, the objectives of this review, are 1) to describe the biological role of SI, 2) to describe the metabolic impact of the Arctic SI LoF variant, 3) to reflect on potential mechanisms linking reduced SI function to metabolic health, and 4) to discuss what knowledge is necessary to properly evaluate whether SI inhibition is a potential therapeutic target for improving cardiometabolic health.
gene therapies
2024-04-22 | Sucrase isomaltase dysfunction influences dietary sucrose intake and preference
Abstract Objective To characterise the role of Sucrase-isomaltase (SI) in regulating dietary behaviours, such as sweet preference and food liking in Si knockout (Sis-KO) mice and in population-based cohorts from Greenland and the UK. Design We profiled the appetitive and post-ingestive response to dietary carbohydrates in SI knockout (Sis-KO) mice. Alongside this, we conducted detailed dietary analysis of 45 foods in two Greenlandic population-based cohorts (IHIT, n=2778 and 68 foods, and B2018, n=2203 and 45 foods) with the presence of a common (allele frequency = 14.3%) SI Loss of function (LoF) variant, c.273-274delAG. Finally, we explored the association between SI hypomorphic variants, liking of 140 foods, and sucrose content using data from 134,766 UKBB participants with exome sequencing and questionnaire data available. Results Sucrose naïve Sis-KO mice had a significantly reduced intake of dietary sucrose, and preference for 10% liquid sucrose, in two-bottle preference studies. Mechanistically, oral administration of the short-chain fatty acid acetate reduced sucrose-preference in wild-type mice. In Greenlandic LoF homozygous carriers we show that the previously reported reduction in sugar intake may primarily be explained by a lower intake of cake and pastries, and of candy and chocolate and that added sugar is the main factor explaining these associations. In the UKBB, a negative association with “cake icing”, the food with the highest sucrose content per 100g, was detected in SI hypomorphic carriers, as well as in sensitivity analyses conducted only including carriers of known CSID LoF variants. Further, a negative linear relationship was also observed between the effect estimates of hypomorphic SI variants on food liking and the estimated sucrose content per 100g of 88 sucrose-containing foods, indicating that food dislike in SI carriers correlates with the amount of sucrose in food. Conclusion Collectively, we demonstrated that genetic variation in the SI gene is associated with significant changes in sucrose preference, characterised by a rapid avoidance of dietary sucrose in Sis-KO mice, as well as lower consumption and increased disliking of sucrose rich foods in Greenlanders and Europeans, respectively. This work demonstrates that genetic variation in the SI gene may impact physiology beyond the gastrointestinal tract and suggest the possibility to target SI to reduce the preference, and intake, of dietary sucrose with implications for digestive and metabolic health.
proteins
2026-02-09 | A NOVEL HETEROZYGOUS SI GENE MUTATİON (C.1783G>T; P.G595X) İN A CHİLD WİTH CLİNİCAL FEATURES OF CONGENİTAL SUCRASE-ISOMALTASE DEFİCİENCY: A CASE REPORT
ABSTRACT Congenital sucrase–isomaltase deficiency (CSID) is increasingly recognized across a broad clinical spectrum, including milder presentations associated with heterozygous SI variants. Case: In this report, a child with chronic abdominal pain, bloating, frequent loose stools and recurrent perianal dermatitis is presented. Genetic testing identified a novel heterozygous nonsense SI variant, c.1783G>T (p.Gly595X). Cascade testing revealed the same variant in his father, who had intermittent loose stools, postprandial bloating, recurrent oral aphthae and IBS-like symptoms, suggesting a mild phenotype. Initiation of oral sacrosidase resulted in marked improvement in stool frequency, abdominal symptoms and perianal dermatitis. Conclusion: This case illustrates the clinical relevance of heterozygous SI variants and expands the mutational spectrum of CSID. The findings underscore the importance of considering SI-related carbohydrate malabsorption in children with chronic loose stools and functional gastrointestinal symptoms when routine investigations are unrevealing. KEYWORDS; Sucrase-isomaltase deficiency, SI gene, Carbohydrate malabsorption, Chronic diarrhea, Nonsense mutation, Sacrosidase therapy
2025-06-06 | Little Patients Big Discoveries: Potential Pediatric to Adult Neurogastroenterology Translation.
Pediatric neurogastroenterology conditions, including disorders of gut-brain interaction and motility disorders, affect millions of children worldwide. Owing to limited pediatric data, reference ranges and management are often extrapolated from adult studies. We review 4 pediatric neurogastroenterology areas where clinical science may translate and inform adult gastroenterology. Sucrase-isomaltase deficiency can be diagnosed through disaccharidase enzyme testing from duodenal mucosal biopsies. Dietary restriction and sacrosidase supplementation are effective, based on randomized controlled trials, in children with genetic sucrase-isomaltase deficiency; however, they remain to be rigorously studied in adults. Gastric emptying breath testing in large cohorts of children reinforces the importance of biological sex, puberty, and size while deriving normative reference values. Further study of gastric emptying breath testing in adults may help determine the influence of sex and hormones on gastric emptying rates, offering an opportunity to develop tailored reference ranges. Antegrade continence enema therapy is the most common reversible surgical treatment for children with chronic constipation, with high rates of efficacy. Few studies have investigated the efficacy of antegrade continence enema in adult populations. Auricular neurostimulation through percutaneous electrical nerve field stimulation is US Food and Drug Administration approved for use in adolescents with irritable bowel syndrome and functional dyspepsia based on sham-controlled, randomized trials with emerging efficacy data in other pediatric disorders of gut-brain interaction. To date, efficacy studies using auricular neurostimulation in adults with gastrointestinal disorders have not been performed. These areas highlight how pediatric neurogastroenterology generates discoveries with the potential to guide approaches in adult populations, underscoring the bidirectional value of translational clinical science.
2025-04-18 | Demystifying Carbohydrate Maldigestion: A Clinical Review.
Carbohydrate intolerance is a poorly understood and potentially overlooked cause of unexplained gastrointestinal symptoms, particularly among patients with disorders of gut-brain interaction. Symptoms related to carbohydrate intolerance arise from bacterial fermentation of unabsorbed carbohydrates leading to increased gases and osmotic load within the gastrointestinal tract. This mechanism is shared across various carbohydrates, including lactose, sucrose, maltose, fructose, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Primary forms of carbohydrate maldigestion typically affect one specific type of carbohydrate and result from inherited defects in specific brush-border enzymes or transport mechanisms, whereas secondary, or acquired, forms of carbohydrate maldigestion can arise from conditions that affect the structural integrity or function of the pancreas and small intestine. Although confirmation of a disaccharidase deficiency does not imply clinical relevance, obtaining a careful patient history with appropriate use of breath testing, duodenal disaccharidase assay, and response to dietary modification can help identify patients whose symptoms are associated with carbohydrate maldigestion and who may benefit from treatment. Dietary modification remains the cornerstone of therapy for patients with carbohydrate intolerance and should focus on determining the most liberal diet for patients that allows symptom control. Given the complexity and time-consuming nature of this process, clinicians are encouraged to engage the help of dietitians with expertise in the treatment of disorders of gut-brain interaction where available. Enzyme replacement therapy can also be an important adjunct to dietary management, with sacrosidase improving symptoms in sucrase-isomaltase deficiency and helping patients to liberalize their diet.
2025-04-12 | Invertase is an effective and cost-efficient alternative to sacrosidase oral solution for sucrase deficiency: a cohort study.
This study aims to evaluate the effectiveness of invertase as an alternative to sacrosidase solution for treating sucrase deficiency in paediatric patients and assess the prevalence of disaccharidase deficiencies in a tertiary care setting. A single-centre, retrospective study was conducted at the Royal Hospital for Children, Glasgow. Patients with low disaccharidase enzyme assay results, confirmed by duodenal biopsy and with normal duodenal histology, taken between 01 January 2011 and 31 August 2019, were included. Data collected included patient demographics, symptomatology, laboratory results and outcomes. The efficacy of invertase supplementation was assessed based on global clinician assessment and improvements in diarrhoea. An estimated treatment cost of invertase versus Sucraid (sacrosidase oral solution) is provided. Of 268 biopsy results from 245 patients, 38% showed low disaccharidase activity, with combinations of sucrase, maltase and lactase deficiencies observed in 19.4%, 25.0% and 29.9% of cases, respectively. Invertase was administered to nine patients with low sucrase. Following invertase treatment, 4/9 (44%) of patients experienced symptom resolution, 4/9 (44%) had a partial response and 1/9 (11%) had no response. Diarrhoea resolved or significantly improved in 8/9 (89%) of patients. The cost of invertase treatment was significantly lower than sacrosidase oral solution, with an estimated yearly cost of £1972 compared with £51 938 for sacrosidase oral solution. Invertase is an effective and cost-efficient alternative to sacrosidase for treating sucrase deficiency in paediatric patients. The study highlights the need for further prospective research to establish the prevalence of disaccharidase deficiencies and to optimise treatment strategies.
2024-12-10 | Frequency of Congenital Sucrase-Isomaltase Deficiency by Whole Exome Sequencing: Is It Really Rare?
Aim: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disease with a mutation in the sucrase-isomaltase (SI) gene and disaccharide maldigestion. With limited data, the estimated incidence of this disease is 57.59/10⁶ births and its heterozygosity rate is 1/132. We aimed to evaluate cases who underwent whole exome sequencing (WES) analysis in the medical genetics unit with regards to the frequency and clinic of CSID. Materials and Methods: The patients’ files who underwent WES between 2018-2023 were evaluated retrospectively. The demographic characteristics, complaints, physical examination, and laboratory findings of those patients with SI gene mutations were recorded. Cases with mutations were recontacted and symptom questioning was performed. Results: Mutations were detected in 25 (8.3%) of 300 patients who underwent WES analysis. One case had a compound heterozygous mutation, while 24 cases were heterozygous. The mean age was 22.4±17.6 years (1.8-52 years) and 16 (64%) were females. Nine of the cases (36%) were symptomatic. Conclusion: Data on the frequency of CSID are insufficient and variable in the literature. The SI heterozygosity rate in our study was higher than some studies. There were similar rates when compared to the study conducted on symptomatic pediatric patients in our country. Although the data of our study includes a heterogeneous group to evaluate the frequency of CSID, it consists of a group with suspected genetic diseases rather than healthy individuals. Therefore, large-scale population-based studies are needed.
small molecules
2026-04-18 | Dietary effect on glucose homeostasis is modulated by a loss-of-function variant in the sucrase-isomaltase gene: a randomised, dietary crossover intervention in Inuit.
Homozygous carriers of a loss-of-function variant in the sucrase-isomaltase (SI) gene (c.273_274delAG) are unable to digest sucrose and parts of starch. The variant is common only in Indigenous Arctic populations such as the Greenlandic Inuit and has been associated with a healthier metabolic profile. In a unique gene-diet intervention, we aimed to study whether the SI genotype modulates the effect of two different diets on glucose homeostasis and lipids. A genotype-based randomised crossover trial was conducted in homozygous SI carriers and non-carriers in Nuuk and Maniitsoq (Greenland), with two 3 day interventions and a 7 day wash-out period. Participants were ≥18 years, had no gastrointestinal disorders, diabetes nor carried an Inuit-specific high-risk type 2 diabetes variant in TBC1D4. The interventions were as follows: a Greenlandic fish- and meat-rich diet; and an isoenergetic Western diet with 11% energy from sucrose. The order of the diets was randomised by the participants using a dice and participants and personnel were not blinded. The primary outcome was glucose variability measured as CV. Fasting blood samples were drawn before and after each intervention for measurement of lipids, insulin and C-reactive protein. We assessed genotype × diet interaction effects using linear mixed models. The study was reported in accordance with the CONSORT 2010 statement: extension to randomised crossover trials and the consolidated criteria for strengthening reporting of health research involving Indigenous peoples (the CONSIDER statement). Seventeen carriers and 16 non-carriers completed the intervention. CV was higher on the Western diet than on the Greenlandic diet for non-carriers (β=5.23% [95% CI 3.02, 7.45]) but not for the carriers (β 1.27% [-0.86, 3.4]). Carriers had a 20% lower CV on the Western diet compared with non-carriers (pgenotype×diet=0.015). Carriers had lower fasting insulin levels than non-carriers at baseline, and the Greenlandic diet decreased the levels in non-carriers by 22.7 pmol/l (95% CI 5.1, 40.3) but not in carriers (pgenotype×diet=0.009). We observed no SI × diet interaction effects on lipids levels. Homozygous loss-of-function SI carriers show better glycaemic management than non-carriers on a Western diet, suggesting SI inhibition as a potential treatment target. ClinicalTrials.gov NCT05375656 FUNDING: Independent Research Fund Denmark, Greenland Research Council and Brugseni.
2025-07-30 | The Hypoglycaemic Effects of the New Zealand Pine Bark Extract on Sucrose Uptake and Glycaemic Responses in Healthy Adults-A Single-Blind, Randomised, Placebo-Controlled, Crossover Trial.
The New Zealand pine bark has been demonstrated in vitro to inhibit digestive enzymes involved in carbohydrate digestion (alpha-amylase, alpha-glucosidase, and dipeptidyl-peptidase 4 (DPP-4)). This study aims to investigate the inhibitory effects of the New Zealand pine bark on sucrose uptake and glycaemic responses in humans. A single-blind, randomised, placebo-controlled, crossover trial was carried out involving healthy adults (n = 40 (M: 12, F: 28), 30.1 ± 1.3 years, BMI 23.4 ± 0.5 kg/m2, HbA1c 32.5 ± 0.6 mmol/mol, FBG 4.7 ± 0.1 mmol/L). A control (75 g of sucrose powder only), and two doses of the pine bark extract (50 and 400 mg) were provided on separate occasions, with 75 g of sucrose mixed in 250 mL of water. Blood samples were collected at -10, 0, 15, 30, 45, 60, 90, and 120 min via a finger prick test. A linear mixed model for repeated measures (SPSS v30, IBM) was applied, and data presented as model-adjusted mean ± SEM. Compared to control (247.5 ± 14.0 mmol/L⋅min), the iAUCglucose was significantly reduced with the 400 mg dose (211.8 ± 13.9 mmol/L⋅min, 14.4% reduction, and p = 0.037), but not with 50 mg dose (220.8 ± 14.2 mmol/L⋅min, 10.8% reduction, and p = 0.184). Compared to control (9.1 ± 0.2 mmol/L), glucose peak value was significantly reduced with the 50 mg dose (8.6 ± 0.2 mmol/L, 5.5% reduction, and p = 0.016) but not with the 400 mg dose (8.7 ± 0.2 mmol/L, 4.4% reduction, and p = 0.093). There were no statistically significant changes in postprandial insulin levels with the pine bark extract compared to control. The New Zealand pine bark extract attenuated sucrose uptake with improved glycaemic responses, and may therefore be useful as a hypoglycaemic adjunct to the diet.
2024-01-07 | Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose
Sucrose is a disaccharide that is degraded into fructose and glucose in the small intestine. High-sucrose and high-fructose diets have been reported, using two-dimensional imaging, to alter the intestinal morphology and the expression of genes associated with sugar transport, such as sodium glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5). However, it remains unclear how high-fructose and high-sucrose diets affect the expression of sugar transporters and the intestinal morphology in the whole intestine. We investigate the influence of a chronic high-sucrose diet on the expression of the genes associated with sugar transport as well as its effects on the intestinal morphology using 3D imaging. High sucrose was found to increase GLUT2 and GLUT5 mRNA levels without significant changes in the intestinal morphology using 3D imaging. On the other hand, the delay in sucrose absorption by an α-glucosidase inhibitor significantly improved the intestinal morphology and the expression levels of SGLT1, GLUT2, and GLUT5 mRNA in the distal small intestine to levels similar to those in the proximal small intestine, thereby improving glycemic control after both glucose and sucrose loading. These results reveal the effects of chronic high-sugar exposure on glucose absorption and changes in the intestinal morphology.
2023-12-13 | Tune in to the terrific applications of turanose
Abstract Turanose, a rare sugar with low calorific value and glycemic index, used as an alternative to sucrose and other artificial sweeteners. The occurrence of turanose is in limited quantities, especially found in honey. Thus, it should be produced by either chemical or biological means. Turanose is released as a by-product during synthesis of the linear α -(1,4)-glucan from sucrose by the action of amylosucrase. In recent times, turanose attracted interest in several industries such as agricultural, food, and pharmaceuticals due to its feasible production. Hence, this review outlines about the history of turanose, its physiochemical properties, production along with inhibition and inducing effects. It is high time to tune in the terrific applications of turanose, as it retains the potential for more than a century of discovery, since 1889. These applications include detection of pathogens, facilitation of cellular respiration, regulation of inflammation, authentication of honey, phagodeterrency effects, osmoprotection, stabilization of therapeutical proteins, and edibility enhancement of foods.
2023-03-01 | Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives
Genetic variants causing loss of sucrase-isomaltase (SI) function result in malabsorption of sucrose and starch components and the condition congenital sucrase-isomaltase deficiency (CSID). The identified genetic variants causing CSID are very rare in all surveyed populations around the globe, except the Arctic-specific c.273_274delAG loss-of-function (LoF) variant, which is common in the Greenlandic Inuit and other Arctic populations. In these populations, it is, therefore, possible to study people with loss of SI function in an unbiased way to elucidate the physiological function of SI, and investigate both short-term and long-term health effects of reduced small intestinal digestion of sucrose and starch. Importantly, a recent study of the LoF variant in Greenlanders reported that adult homozygous carriers have a markedly healthier metabolic profile. These findings indicate that SI inhibition could potentially improve metabolic health also in individuals not carrying the LoF variant, which is of great interest considering the massive number of individuals with obesity and type 2 diabetes worldwide. Therefore, the objectives of this review, are 1) to describe the biological role of SI, 2) to describe the metabolic impact of the Arctic SI LoF variant, 3) to reflect on potential mechanisms linking reduced SI function to metabolic health, and 4) to discuss what knowledge is necessary to properly evaluate whether SI inhibition is a potential therapeutic target for improving cardiometabolic health.
gene therapies
2024-04-22 | Sucrase isomaltase dysfunction influences dietary sucrose intake and preference
Abstract Objective To characterise the role of Sucrase-isomaltase (SI) in regulating dietary behaviours, such as sweet preference and food liking in Si knockout (Sis-KO) mice and in population-based cohorts from Greenland and the UK. Design We profiled the appetitive and post-ingestive response to dietary carbohydrates in SI knockout (Sis-KO) mice. Alongside this, we conducted detailed dietary analysis of 45 foods in two Greenlandic population-based cohorts (IHIT, n=2778 and 68 foods, and B2018, n=2203 and 45 foods) with the presence of a common (allele frequency = 14.3%) SI Loss of function (LoF) variant, c.273-274delAG. Finally, we explored the association between SI hypomorphic variants, liking of 140 foods, and sucrose content using data from 134,766 UKBB participants with exome sequencing and questionnaire data available. Results Sucrose naïve Sis-KO mice had a significantly reduced intake of dietary sucrose, and preference for 10% liquid sucrose, in two-bottle preference studies. Mechanistically, oral administration of the short-chain fatty acid acetate reduced sucrose-preference in wild-type mice. In Greenlandic LoF homozygous carriers we show that the previously reported reduction in sugar intake may primarily be explained by a lower intake of cake and pastries, and of candy and chocolate and that added sugar is the main factor explaining these associations. In the UKBB, a negative association with “cake icing”, the food with the highest sucrose content per 100g, was detected in SI hypomorphic carriers, as well as in sensitivity analyses conducted only including carriers of known CSID LoF variants. Further, a negative linear relationship was also observed between the effect estimates of hypomorphic SI variants on food liking and the estimated sucrose content per 100g of 88 sucrose-containing foods, indicating that food dislike in SI carriers correlates with the amount of sucrose in food. Conclusion Collectively, we demonstrated that genetic variation in the SI gene is associated with significant changes in sucrose preference, characterised by a rapid avoidance of dietary sucrose in Sis-KO mice, as well as lower consumption and increased disliking of sucrose rich foods in Greenlanders and Europeans, respectively. This work demonstrates that genetic variation in the SI gene may impact physiology beyond the gastrointestinal tract and suggest the possibility to target SI to reduce the preference, and intake, of dietary sucrose with implications for digestive and metabolic health.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Congenital sucrase-isomaltase deficiency, including 1 approved therapy.
2 orphan drug designations for Congenital sucrase-isomaltase deficiency, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Sacrosidase | proteins | EMA | — | QOL Therapeutics Holdings Limited |
Sacrosidase [Sucraid] | proteins | FDA | Approved | QOL Medical, LLC |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.