Sucrase-isomaltase Deficiency Research Articles

Recurrent calcium oxalate calculi: the culprit in disguise.

Congenital sucrase isomaltase deficiency (CSID) is a rare autosomal recessive monogenic disorder of small intestinal malabsorption and manifests typically in early childhood with chronic osmotic diarrhoea. Though there have been case reports in adults presenting with hypercalcemia and renal calculi in CSID, this is quite rare in children. We hereby report a 6-year-old boy who presented with recurrent episodes of calcium oxalate calculi without any gastrointestinal symptoms and was confirmed as having sucrase isomaltase deficiency by genetic analysis.

S4748 Hidden Malabsorptive Syndrome: Sucrase-Isomaltase Deficiency Finally Unveiled in Adulthood

S4748 Hidden Malabsorptive Syndrome: Sucrase-Isomaltase Deficiency Finally Unveiled in Adulthood

Disaccharidase deficiencies and gastrointestinal symptoms in patients referred to gastroscopic examination: a single center study from Norway

Objective Gastrointestinal illnesses have been reported in relation to low disaccharidase activity, yet both the prevalence of disaccharidase deficiency and its association with gastrointestinal symptoms and irritable bowel syndrome (IBS) are largely unknown. We aimed to determine the association between low activity of disaccharidase enzymes on gastrointestinal symptoms and presence of IBS. Methods Patients referred for gastroscopic examination due to gastrointestinal complaints were consecutively included. A pinch biopsy was taken from the distal part of duodenum, and disaccharidase activity was measured using the Dahlqvist method. Gastrointestinal symptom severity was measured using IBS-Symptom Severity Score (IBS-SSS). Results A total of 40 patients were included. Disaccharidase deficiency was detected in 24 patients (60%). Half of the patients (n = 21) had IBS according to Rome IV criteria. A majority (75%) of all patients reported moderate to severe gastrointestinal symptoms. Moderate to severe gastrointestinal symptoms were reported by 16 patients (67%) with disaccharidase deficiency and in 14 patients (88%) with normal disaccharidase activity. Lactase deficiency was detected in 22 patients (55%), maltase deficiency in 11 patients (28%), sucrase deficiency in 9 patients (23%), isomaltase deficiency in 13 patients (33%) and glucoamylase deficiency in 12 patients (30%). The activity of all enzymes was reduced in 8 patients (20%). Degree of disaccharidase deficiency was not associated with either the severity of gastrointestinal symptoms or the diagnosis of IBS. Enzymes levels were not associated with gastrointestinal symptom scores. Conclusion Our findings did not reveal any association between biochemically measured disaccharidase deficiency and gastrointestinal symptoms or the presence of IBS.

GENETIC DETERMINANTS OF CARBOHYDRATE METABOLISM: INTRA- AND INTERETHNIC VARIABILITY OF THE LACTASE LCT, TREHALASE TREH AND SUCRASE-ISOMALTASE SI GENES IN THE EVENKI AND OTHER INDIGENOUS PEOPLES OF SIBERIA

Introduction. The authors consider the features of genetic determinants of disaccharide assimilation as the corollary of adaptation to the environment. The aim of the study was to assess the polymorphism of the genes that determine activity of disaccharidase enzymes lactase (LCT, rs4988235), trehalase (TREH, rs2276064) and sucrase-isomaltase (SI, rs781470490) in different territorial groups of Evenks. Materials and methods. Biomaterial samples from 1365 unrelated individuals representing 15 ethno-territorial population groups in European Russia, Siberia, and the Far East of the Russian Federation were genotyped. "Focus" groups include "Western" (N=65), "Transbaikal" (N=50), and "Okhotsk" (N=81) Evenks (Krasnoyarsk Krai, Northern Transbaikalia, Okhotsk-Aldan region). The other study groups allow us to assess the specificity of the distribution of genetic determinants of disaccharide assimilation in populations that differ from racial, ecological, and subsistence perspectives. Results. The Evenki territory subgroups do not differ from each other in terms of allele frequencies and genotype distribution of LCT (p>0.2) and TREH (p>0.8) and are similar to Yakuts, Buryats, Mongols, and populations of the Far East and Chukotka. The SI delAG deletion was not found in the Western Evenki subgroup. Discussion. A question of similarity between taiga hunters Evenks to cattle breeders Buryats, Mongols, and Yakuts in terms of C*LCT frequencies requires further elaboration. Possible explanations may include a weakening of selection for the T*LCT allele due to the shift in traditional diet toward replacement of fresh milk with fermented dairy products, high activity of specific intestinal microflora, or the existence of other lactase synthesis genetic determinants, besides LCT*C/T-13910. The evolutionary origins of the clinal variation in the TREH gene allele frequencies, which appears to be associated with the expression of the Mongoloid ancestral component in the gene pool of populations in Northern Eurasia, remain unclear. It seems appropriate to conduct genetic screening in the indigenous populations of the Russian Far East in order to assess the prevalence of SI delAG deletion as an inducer of the sucrase-isomaltase deficiency.

Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations.

Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea. In this study, the genotype-phenotype relationships of close relatives of an index case with congenital sucrase-isomaltase deficiency were investigated. A 23-month-old female patient with a sucrase-isomaltase gene c.317G>A (p.C106Y) homozygous mutation was diagnosed as an index case and her pedigree analysis was performed subsequently. The family members with and without sucrase- isomaltase gene mutations were compared in terms of clinical symptoms. The study included 109 cases [mean age ± SD: 22.6 ± 17.2 years (0.1-75 years), 61 males (56%)] of 130 family members of the index case. Sucrase-isomaltase gene c.317G>A (p.C106Y) heterozygous mutation was detected in 27 cases (24.7%); 14 (51.9%) were male and had a mean age of 23.2 ± 18.3 years. The most common complaints of 12 (44.4%) symptomatic patients with mutations were abdominal pain (37%), gas irritability (33.3%), bloating (22.2%), and foul-smelling stools (18.5%). Compared with the cases without mutation, a statistically significant difference was observed in the incidence of gas irritability, foul-smelling stool, ≥2 gastrointestinal symptoms, postprandial complaints, and food allergy (P = .005, P = .047, P = .049, P = .017, P = .021, respectively). Sacrosidase enzyme replacement was applied to 7 patients whose symptoms did not improve with dietary elimination. Clinical response was obtained after enzyme treatment. Despite its autosomal recessive inheritance, congenital sucrase-isomaltase deficiency can also be symptomatic in heterozygous individuals. Further studies are required to clarify the genotype-phenotype relationship and management of the disease.

Congenital sucrase–isomaltase deficiency in Türkiye; a single center experience

Background Congenital sucrase–isomaltase deficiency (CSID) is a rare inherited carbohydrate malabsorption disorder caused by sucrase–isomaltase (SI) gene variants. In CSID, an autosomal recessively inherited disease, symptoms can also be seen in individuals with heterozygous mutations. Methods The variant spectrum was evaluated retrospectively in individuals who presented with chronic diarrhea between 2014 and 2022 and had undergone genetic testing of the SI gene considering CSID due to diet-related complaints. Results Ten patients with chronic diarrhea were genetically evaluated with SI gene sequencing. In patients diagnosed with CSID and whose symptoms improved with enzyme replacement therapy, the genetic mutation zygosity was found to be heterozygous at a rate of 90%. In 10% of the patients, the mutation was homozygous. Limiting consuming sucrose and isomaltose foods reduced the patients’ complaints, but the symptoms did not disappear completely. With the initiation of sacrosidase enzyme replacement therapy, the patient’s complaints completely disappeared. Conclusion In CSID, defined as an autosomal recessive disease, clinical symptoms can also be seen in heterozygous cases previously described as carriers, and these patients also benefit from sacrosidase enzyme replacement therapy. In light of these findings, the autosomal recessive definition of CSID does not fully characterize the disease. What is Known: CSID is a rare inherited carbohydrate malabsorption disorder caused by sucrase–isomaltase gene variants. In congenital sucrase–isomaltase deficiency, an autosomal recessively inherited disorder, symptoms can also be seen in individuals with heterozygous mutations. What is new: Severe disease symptoms can also be seen in heterozygous cases, which were thought to be carriers because the disease was previously described as autosomal recessive. Sacrosidase enzyme replacement therapy also eliminates the disease symptoms in patients with heterozygous CSID mutations. This is the second study on sucrase–isomaltase enzyme deficiency pediatric groups in Türkiye and Europe.

Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.

Healthcare Burden in Greenland of Gastrointestinal Symptoms in Adults with Inherited Loss of Sucrase-Isomaltase Function.

Congenital sucrase isomaltase deficiency (CSID) is in general a very rare disease. However, 2-3% of the Greenlandic population are homozygous (HO) carriers of an Arctic-specific loss-of-function (LoF) variant in the sucrase-isomaltase (SI) encoding gene, causing CSID. The condition is characterized by gastrointestinal symptoms such as stomachache, diarrhea, and weight loss when consuming sucrose, the most common dietary sugar. However, the awareness of the condition in the population and the healthcare system seems to be limited, potentially leading to a higher healthcare burden. Hence, we aimed to investigate whether HO-carriers visit the healthcare system more with gastrointestinal symptoms compared to the control groups by using registry data. We performed a case-control study identifying cases and controls using genotype information from the 1999-2001 and 2005-2010 Greenlandic health population cohorts. The cases were defined as HO LoF SI-carriers and controls were defined as non-carriers and were matched (1:1) on sex, age, place of residence, and European genetic admixture. We used electronic medical records to assess the number of electronic medical record contacts (EMRc) related to gastrointestinal symptoms and the number of gastrointestinal-related diagnostic procedures. A total of 80 HO-carriers and 80 non-carriers were included. The HO-carriers had 19% more EMRc related to gastrointestinal symptoms (IRR, 1.19, 95% CI [1.02;1.40], p=0.02) and had a 41% higher incidence of gastrointestinal related diagnostic procedures compared to controls (IRR, 1.41, 95% CI [1.05-1.92], p=0.02). Only one HO-carrier was aware of the condition according to the electronic medical records. HO-carriers of the LoF SI-variant had both significantly more gastrointestinal-related EMRc and significantly more diagnostic procedures conducted due to gastrointestinal symptoms. Only one HO-carrier was aware of the condition. Given the high prevalence of HO-carriers in the Greenlandic population, we anticipate that diagnosing more patients with CSID and providing dietary advice could potentially reduce symptom burden and healthcare visits among HO-carriers.

Genetics of sucrose metabolism disorders in different population groups

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

Impaired digestive function of sucrase-isomaltase in a complex with the Greenlandic sucrase-isomaltase variant

Sucrase isomaltase (SI) is the most prominent disaccharidase in the small intestine. Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene.A homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), has been identified in CSID in the Greenlandic population. This variant eliminates the luminal domain of SI and results in loss of its digestive function.Surprisingly, the truncated mutant is transport-competent and localized at the cell surface; it interacts avidly with wild type SI and negatively impacts its enzymatic function.The data propose that heterozygote carriers of p.Gly92Leufs*8 may also present with CSID symptoms.

A starch- and sucrose-reduced diet may lead to improvement of intestinal and extraintestinal symptoms in more conditions than irritable bowel syndrome and congenital sucrase-isomaltase deficiency

ObjectivesA starch- and sucrose-reduced diet has been found to improve gastrointestinal and extraintestinal symptoms in irritable bowel syndrome, as well as reduce weight and improve psychological well-being. Our hypothesis was that a starch- and sucrose-reduced diet would also be beneficial in other conditions with similar symptoms. The aim of the present research letter was to describe the role of a starch- and sucrose-reduced diet in a pilot project in patients with diarrhea having varying causes. MethodsOne man, age 36 y, suffering from functional diarrhea and one woman, 56 y, suffering from microscopic colitis, were randomized to a starch- and sucrose-reduced diet for 4 wk. At baseline, dietary information was given, and blood samples collected. Weight and waist circumference were measured. The participants completed the irritable bowel syndrome severity scoring system for evaluating specific gastrointestinal and extraintestinal symptoms and visual analog scale for irritable bowel syndrome for evaluation of specific gastrointestinal symptoms and psychological well-being. The degrees of satiety and sweet craving were measured on visual analog scales. After 4 wk, all procedures were repeated. ResultsWeight, body mass index, and waist circumference were decreased during the intervention. The total amount of gastrointestinal symptoms was decreased in the participants with functional diarrhea, and diarrhea and bloating were decreased in both participants. Both had reduced extraintestinal symptoms and improved psychological well-being. Blood levels had mainly unchanged or slightly increased values of measurements reflecting nutrient intake. ConclusionsA starch- and sucrose-reduced diet may lead to weight reduction, reduced symptoms, and improved well-being in several patient categories, not only in patients suffering from irritable bowel syndrome. Future randomized trials should be done.

Prevalence of congenital sucrase-isomaltase deficiency in Turkey may be much higher than the estimates

Prevalence of congenital sucrase-isomaltase deficiency in Turkey may be much higher than the estimates

Sucraid (sacrosidase) is the only treatment for CSID: should there be a better option?

Sucraid (sacrosidase) is the only treatment for CSID: should there be a better option?

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.

The effect of sucrase-isomaltase deficiency on metabolism, food intake and preferences: protocol for a dietary intervention study

ABSTRACT In Greenland, traditional marine foods are increasingly being replaced by sucrose- and starch-rich foods. A knock-out c.273_274delAG variant in the sucrase-isomaltase (SI) gene is relatively common in Greenland, with homozygous carriers being unable to digest sucrose and some starch. The variant is associated with a healthier metabolic phenotype in Greenlanders, which is confirmed by SI-knockout mice. We aim to assess if the healthy phenotype is explained by metabolic and microbial differences and if food and taste preferences differ between SI-genotypes. This paper describes the protocol for a randomised cross-over trial conducted in Greenland in 2022 with two dietary interventions of three days; a traditional meat- and fish-rich diet and a starch-rich Western diet with 11 energy% sucrose. The power calculation showed that 22 homozygous SI-carriers and 22 non-carriers were sufficient to detect a 0.5 mmol/L difference in glycaemic variability (80% power, α=0.05). We enrolled 18 carriers and 20 non-carriers. We examined food preferences at baseline and collected samples before and after each intervention for metabolic, metabolome, and microbiome profiling. Analyses of samples have not been completed yet. The Ethics Committee of Greenland approved the study. Results will be disseminated in international peer-reviewed journals and to the general Greenlandic population. NCT05375656.

Development of a legume-enriched feed for treatment of severe acute malnutrition.

Background: Outcomes in children hospitalised with severe acute malnutrition (SAM) remain poor. The current milk-based formulations focus on restoring weight-gain but fail to address modification of the integrity of the gut barrier and may exacerbate malabsorption owing to functional lactase, maltase and sucrase deficiency. We hypothesise that nutritional feeds should be designed to promote bacterial diversity and restore gastrointestinal (GI) barrier function. Methods: Our major objective was to develop a lactose-free, fermentable carbohydrate-containing alternative to traditional F75 and F100 formulae for the inpatient treatment of SAM. New target nutritional characteristics were developed and relevant food and infant food specific legislation were reviewed. Suitable certified suppliers of ingredients were identified. Processing and manufacture steps were evaluated and optimised for safety (nutritional, chemical and microbiological), and efficacy at meeting target characteristics (lactose-free, containing resistant starch 0.4-0.5% final product weight). Results: A final validated production process was developed and implemented to produce a novel food product for the inpatient treatment of SAM in children in Africa designed to reduce risk of osmotic diarrhoea and support symbiotic gut microbial populations. The final product matched the macronutrient profile of double-concentrated F100, adhered to all relevant legislation regulating infant foods, was lactose free, and contained 0.6% resistant starch. Chickpeas were selected as the source of resistant starch, since they are widely grown and eaten throughout Africa. Micronutrient content could not be matched in this ready-to-use product, so this was replaced at the point of feeding, as was fluid lost through concentration. Conclusions: The processes and product described illustrate the development steps for a novel nutritional product. The new feed product was ready for evaluation for safety and efficacy in a phase II clinical trial in Ugandan children admitted to hospital with SAM (Modifying Intestinal MicroBiome with Legume-Based feed 2: MIMBLE feed 2 (ISRCTN10309022)).

Estimating the prevalence of congenital disaccharidase deficiencies using allele frequencies from gnomAD

Background: There are currently three known congenital disaccharidase deficiencies: congenital lactase deficiency (CLD), congenital sucrase-isomaltase deficiency (CSD), and congenital trehalase deficiency (CTD). No congenital deficiency has been described for maltase-glucoamylase (MGAM).Methods: A literature search was performed in PubMed for the pathogenic variants CLD, CSD, and CTD and the articles retrieved were analyzed to estimate the prevalence of congenital disaccharidase deficiencies.Results: Based on reported variants, the estimated prevalence was 1.3 per 106 births (95% CI: 1.1–1.7) for CLD, and 31.4 per 106 births (95% CI: 28.3–34.8) for CSD. Using data on previously reported variants and variants predicted to be loss-of-function in gnomAD, the overall estimated prevalence was 2.3 per 106 births (95% CI: 1.9–2.9) for CLD, 57.6 per 106 births (95% CI:52.5–63.2) for CSD, and 9.2 per 106 births (95% CI: 2.5–3.7) for CTD.Conclusion: The prevalence of CSD was found to be relatively high, while for other congenital disaccharidase deficiencies, the estimated prevalence was very low.

Severe pathogenic variants of intestinal sucrase-isomaltase interact avidly with the wild type enzyme and negatively impact its function and trafficking

Sucrase-isomaltase (SI) is the major disaccharidase of the small intestine, exhibiting a broad α-glucosidase activity profile. The importance of SI in gut health is typified by the development of sucrose and starch maldigestion in individuals carrying mutations in the SI gene, like in congenital sucrase-isomaltase deficiency (CSID). Common and rare defective SI gene variants (SIGVs) have also been shown to increase the risk of irritable bowel syndrome (IBS) with symptoms and clinical features similar to CSID and also in symptomatic heterozygote carriers. Here, we investigate the impact of the most abundant and highly pathogenic SIGVs that occur in heterozygotes on wild type SI (SIWT) by adapting an in vitro system that recapitulates SI gene heterozygosity. Our results demonstrate that pathogenic SI mutants interact avidly with SIWT, negatively impact its enzymatic function, alter the biosynthetic pattern and impair the trafficking behavior of the heterodimer. The in vitro recapitulation of a heterozygous state demonstrates potential for SIGVs to act in a semi-dominant fashion, by further reducing disaccharidase activity via sequestration of the SIWT copy into an inactive form of the enzymatic heterodimer. This study provides novel insights into the potential role of heterozygosity in the pathophysiology of CSID and IBS.

Sucrose intolerance in adults with common functional gastrointestinal symptoms

Sucrose intolerance is a form of carbohydrate malabsorption caused by sucrase-isomaltase deficiency that is more common than recognized. Its symptoms include postprandial cramping, bloating, gas, and diarrhea, which are difficult to distinguish from irritable bowel syndrome. The gold standard test for diagnosing sucrase deficiency is a sucrase enzyme assay of duodenal biopsies obtained by endoscopy. Hydrogen-methane or 13C-sucrose breath tests are noninvasive methods to screen for sucrose malabsorption. This chart review included 258 consecutive adults (47 men and 211 women) with chronic unexplained gastrointestinal symptoms and suspected sucrose intolerance who were screened with a hydrogen-methane or 13C-sucrose breath test. The incidence of sucrose malabsorption with two different hydrogen-methane breath tests was 34.4% (21/61) (Commonwealth Diagnostics International, Inc., Salem, MA) and 40% (20/50) (Aerodiagnostics, Concord, MA). The incidence of sucrose malabsorption with the 13C-sucrose breath test was 26.5% (39/147). In a subgroup of patients with positive breath tests and clinical follow-up, counseling regarding diet and/or enzyme replacement led to symptomatic improvement in 26/43 (60%). In conclusion, sucrose malabsorption may present with irritable bowel syndrome symptoms in a proportion of adult patients, and breath tests may be useful in identifying sucrose malabsorption and differentiating it from other gastrointestinal disorders.

Glycogen Storage Disease type IA refractory to cornstarch: Can next generation sequencing offer a solution?

Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase production) which may explain their persistent symptoms. WES confirmed the GSD-Ia diagnosis, with all three probands harboring the homozygous p.R83C variant in G6PC. While no other significant variants were identified for patients A and B, a homozygous p.G276V variant in the SI gene was detected in patient C, establishing the dual-diagnosis of GSD-Ia and Sucrase-Isomaltase Deficiency. To conclude, we suggest that WES should be considered in GSD-Ia patients who show persistent symptoms despite optimal dietary management.