Congenital Glucose-Galactose Malabsorption: A Case With a Novel SLC5A1 Mutation in a Saudi Infant

Alamoudi, Loujen O.; Alfaraidi, Albaraa T.; Althagafi, Samiyah S.; Althaqafy, Majid; Hasosah, Mohammed

doi:10.7759/cureus.18440

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…56,57 Loss of SGLT results in glucose-galactose malabsorption, a rare congenital autosomal recessive disorder characterized by severe diarrhea starting at birth. 53,55 Our common variant analysis detected that having at least one copy of a minor allele at rs130406 in SLC5A1 was associated with 32% decreased risk of having an IBS-C phenotype. In addition, one IBS individual with digenic inheritance in SI and SLC5A1 reported moderate diarrhea, while other IBS symptoms were reported as mild.…”

Section: Discussionmentioning

confidence: 94%

“…We also examined genetic variations in SLC5A1 and SLC2A5 which are involved in glucose, galactose, and fructose intestinal uptake. 53–55 Cellular uptake of glucose is driven by two glucose transport families: sodium driven glucose cotransporters (SGLT) and the facilitative glucose transporters (GLUT) encoded by the solute carrier genes SLC5A1 and SLC5A2 . 56,57 Loss of SGLT results in glucose-galactose malabsorption, a rare congenital autosomal recessive disorder characterized by severe diarrhea starting at birth.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome

Hong,

Schulze,

Copeland

et al. 2023

Preprint

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Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants in TREH, SI, SLC5A1 and SLC2A5 that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB, and SLC5A1) as well as candidate disease genes (MGAM and SLC5A2), providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome

Hong,

Schulze,

Copeland

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Genetic testing is not strictly necessary to establish the diagnosis, but allows the identification of affected individuals early, and exome sequencing is suited to detect or exclude additional monogenic disorders, thus preventing serious complications and improving clinical outcomes [27]. It is highly recommended to confirm the clinical diagnosis by genetic testing and thus provide a basis for genetic counseling, carrier screening, and future family planning.…”

Section: Discussionmentioning

confidence: 99%

SLC5A1 Variants in Turkish Patients with Congenital Glucose-Galactose Malabsorption

Hoşnut,

Janecke,

Şahin

et al. 2023

Genes

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Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 encoding the apical sodium/glucose cotransporter SGLT1. We present clinical and molecular data from eleven affected individuals with congenital glucose-galactose malabsorption from four unrelated, consanguineous Turkish families. Early recognition and timely management by eliminating glucose and galactose from the diet are fundamental for affected individuals to survive and develop normally. We identified novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, which were linked to disease in two families. Stable expression in CaCo-2 cells showed that the p.Ala92Val variant did not reach the plasma membrane, but was retained in the endoplasmic reticulum. The p.Gly43Arg variant, however, displayed processing and plasma membrane localization comparable to wild-type SGLT1. Glycine-43 displays nearly invariant conservation in the relevant structural family of cotransporters and exchangers, and localizes to SGLT1 transmembrane domain TM0. p.Gly43Arg represents the first disease-associated variant in TM0; however, the role of TM0 in the SGLT1 function has not been established. In summary, we are expanding the mutational spectrum of this rare disorder.

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Renal glucosuria in children

Torun Bayram,

Kavukcu

2025

World J Clin Pediatr

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The kidneys play a critical role in maintaining glucose homeostasis. Under normal renal tubular function, most of the glucose filtered from the glomeruli is reabsorbed in the proximal tubules, leaving only trace amounts in the urine. Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced, as seen in familial renal glycosuria (FRG). FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene, which encodes the sodium-glucose cotransporter (SGLT) 2. Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes, and since FRG is often considered an asymptomatic and benign condition, it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes. However, patients with FRG may exhibit clinical features such as lower body weight or height, altered systemic blood pressure, diaper dermatitis, aminoaciduria, decreased serum uric acid levels, and hypercalciuria. Further research is needed to fully understand the pathophysiology, molecular genetics, and clinical manifestations of renal glucosuria.

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Congenital Glucose-Galactose Malabsorption: A Case With a Novel SLC5A1 Mutation in a Saudi Infant

Cited by 4 publications

References 11 publications

Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome

Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome

SLC5A1 Variants in Turkish Patients with Congenital Glucose-Galactose Malabsorption

Renal glucosuria in children

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