Congenital Sucrase‐isomaltase Deficiency

Haberman, Yael; Segni, Ayelet Di; Loberman-Nachum, Nurit; Barel, Ortal; Kunik, Vered; Eyal, Eran; Kol, Nitzan; Hout‐Siloni, Goni; Kochavi, Brigitte; Avivi, Camila; Schvimer, Michael; Rechavi, Gideon; Anikster, Yair; Barshack, Iris; Weiss, Batia

doi:10.1097/mpg.0000000000001424

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…This study also confirmed presence of heterozygous SI gene mutations in symptomatic cases with varied disaccharidase deficiency patterns, including low sucrase with and without low isomaltase, and PDD (3,7,10,32,37). Moreover, 71% of abnormal cases had concurrent lactase deficiency.…”

Section: Discussionsupporting

confidence: 79%

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Sucrase‐isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders

Deb

Campion

Derrick

et al. 2020

J. pediatr. gastroenterol. nutr.

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Objectives: The aim of the study was to determine prevalence and characterize sucrase-isomaltase (SI) gene variants of congenital sucrase-isomaltase deficiency in non-Hispanic white pediatric and young adult patients with functional gastrointestinal disorders (FGIDs), and abnormal sucrase activity on histologically normal duodenal biopsy. Methods: Clinical symptoms and disaccharidase activities data were collected for an abnormal (low) sucrase (≤25.8 U, n = 125) activity group, and 2 normal sucrase activity groups with moderate (≥25.8–≤55 U, n = 250) and high (>55 U, n = 250) sucrase activities. SI gene variants were detected by next-generation sequencing of DNA from formalin-fixed paraffin-embedded tissues of these patients. FGIDs symptoms based on Rome IV criteria and subsequent clinical management of abnormal sucrase activity cases with pathogenic SI gene variants were analyzed. Results: Thirteen SI gene variants were found to be significantly higher in abnormal sucrase cases with FGIDs symptoms (36/125, 29%; 71% did not have a pathogenic variant) compared to moderate normal (16/250, 6.4%, P < 0.001) or high normal (5/250, 2.0%, P < 0.001) sucrase groups. Clinical management data were available in 26 of abnormal sucrase cases, and only 10 (38%) were correctly diagnosed and managed by the clinicians. Concomitant lactase deficiency (24%; 23/97) and pan-disaccharidase deficiency (25%; 13/51) were found in the abnormal sucrase group. Conclusions: Heterozygous and compound heterozygous mutations in the SI gene were more prevalent in cases with abnormal sucrase activity presenting with FGIDs, and normal histopathology. This suggests heterozygous pathogenic variants of congenital sucrase-isomaltase deficiency may present as FGIDs. Concomitant lactase or pan-disaccharidase deficiencies were common in abnormal sucrase cases with SI gene variants.

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Section: Discussionsupporting

confidence: 79%

“…In recent studies, compound and simple heterozygous CSID variants were detected in patients diagnosed with IBS (3,5). Other studies reported high prevalence of sucrase enzyme deficiency in duodenal biopsies from patients with functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and nausea (3,5,7,10,11).…”

Section: What Is Newmentioning

confidence: 99%

Sucrase‐isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders

Deb

Campion

Derrick

et al. 2020

J. pediatr. gastroenterol. nutr.

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“…Patients with an onset of CSID in infancy typically present symptoms that include diarrhea and failure to thrive, as observed in our case. Patients with an onset of CSID in childhood or adulthood present milder symptoms with only chronic diarrhea and have normal growth rates (11). According to a summary of previously reported cases (2,(6)(7)(8)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), the incidence of CSID differs between females and males (19/60) (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Patients with an onset of CSID in childhood or adulthood present milder symptoms with only chronic diarrhea and have normal growth rates (11). According to a summary of previously reported cases (2,(6)(7)(8)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), the incidence of CSID differs between females and males (19/60) (Table 1). However, in some of these cases, sex was not reported.…”

Section: Discussionmentioning

confidence: 99%

Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China

et al. 2021

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Background: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive inherited disease that leads to the maldigestion of disaccharides and is associated with mutation of the sucrase-isomaltase (SI) gene. Cases of CSID are not very prevalent in China or worldwide but are gradually being identified and reported.Case Presentation: We report a case involving a 14-month-old male who presented with failure to thrive that had begun after food diversification and was admitted for chronic diarrhea. We used a whole-exome sequencing (WES) approach to identify mutations in this patient's genome. WES revealed two novel heterozygous mutations in the SI gene, c.2626C > T (p.Q876*) and c.2872C > T (p.R958C), which were confirmed by Sanger DNA sequencing. With a strict sucrose- and starch-restricted diet, the patient's diarrhea was resolved, and he began to gain weight.Conclusions: We report a case of novel variants in the SI gene that caused CSID. This report provides valuable information for the clinical field, especially in China.

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“…The SI gene, which encodes the SI enzyme, is located on chromosome 3 and harbors a number of rare pathogenic mutations across functional domains, including the sucrase domain, the isomaltase domain, the cytosolic tail, the transmembrane domain, the stalk region, and the trefoil 1 domain (Figure 2). [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] These variants are predicted to result in reduced SI function or complete loss of SI function, 26 and thereby CSID.…”

Section: Genetic Variation In the Sucrase-isomaltase Genementioning

confidence: 99%

Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives

Senftleber¹,

Ramne²,

Moltke³

et al. 2023

TACG

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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.

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Congenital Sucrase‐isomaltase Deficiency

Cited by 8 publications

References 22 publications

Sucrase‐isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders

Sucrase‐isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders

Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China

Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives

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