Kidney and vascular function in adult patients with hereditary fructose intolerance

Simons, Nynke; Debray, François Guillaume; Schaper, Nicolaas C.; Feskens, Edith J. M.; Hollak, Carla E. M.; Bons, J; Bierau, Jörgen; Houben, Alfons J.H.M.; Schalkwijk, Casper G.; Stehouwer, Coen D. A.; Cassiman, David; Brouwers, Martijn C.G.J.

doi:10.1016/j.ymgmr.2020.100600

Cited by 10 publications

(10 citation statements)

References 48 publications

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“…It was found that even with a restrictive diet, most patients showed mild signs of liver disease; however, this liver disease was not complemented by damage progression. HFI patients in the same study also exhibited elevated systolic blood pressure, epidermal growth factor receptor (eGFR), and plasma sE-selectin levels compared to healthy controls [ 46 ]. Therefore, when treating HFI patients, the effects of fructose restriction on blood pressure and renal function should also be considered.…”

Section: Fructose Metabolism Disordersmentioning

confidence: 99%

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

et al. 2021

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History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

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Section: Fructose Metabolism Disordersmentioning

confidence: 99%

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

et al. 2021

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“…There is a growing use of fructose, as it is widely used as a food additive, and small amounts of this sugar are hidden in many foods. Thus, it is not surprising that HFI patients develop previously unreported complications, such as liver steatosis [7,9] or signs of proximal tubular dysfunction [10,11].…”

Section: Introductionmentioning

confidence: 99%

Transferrin Isoforms, Old but New Biomarkers in Hereditary Fructose Intolerance

Cano

Alcalde

Bélanger-Quintana

et al. 2021

JCM

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Hereditary Fructose Intolerance (HFI) is an autosomal recessive inborn error of metabolism characterised by the deficiency of the hepatic enzyme aldolase B. Its treatment consists in adopting a fructose-, sucrose-, and sorbitol (FSS)-restrictive diet for life. Untreated HFI patients present an abnormal transferrin (Tf) glycosylation pattern due to the inhibition of mannose-6-phosphate isomerase by fructose-1-phosphate. Hence, elevated serum carbohydrate-deficient Tf (CDT) may allow the prompt detection of HFI. The CDT values improve when an FSS-restrictive diet is followed; however, previous data on CDT and fructose intake correlation are inconsistent. Therefore, we examined the complete serum sialoTf profile and correlated it with FSS dietary intake and with hepatic parameters in a cohort of paediatric and adult fructosemic patients. To do so, the profiles of serum sialoTf from genetically diagnosed HFI patients on an FSS-restricted diet (n = 37) and their age-, sex- and body mass index-paired controls (n = 32) were analysed by capillary zone electrophoresis. We found that in HFI patients, asialoTf correlated with dietary intake of sucrose (R = 0.575, p < 0.001) and FSS (R = 0.475, p = 0.008), and that pentasialoTf+hexasialoTf negatively correlated with dietary intake of fructose (R = −0.386, p = 0.024) and FSS (R = −0.400, p = 0.019). In addition, the tetrasialoTf/disialoTf ratio truthfully differentiated treated HFI patients from healthy controls, with an area under the ROC curve (AUROC) of 0.97, 92% sensitivity, 94% specificity and 93% accuracy.

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“…The mechanism connecting fructose to hypertension is unclear and may be an indirect product of worsened metabolic phenotype. However, there is emerging evidence that fructose metabolism in specific cell types (e.g., kidney/proximal tubule and vascular endothelium) directly promote pathways involved in increased blood pressure, including renal NHE3 upregulation [ 30 – 34 ]. While the decreased incidence of hypertension in participants with two Val49Ile variants in this dataset is encouraging, the lack of additional clinical benefits (e.g., decreased glucose, insulin, and triglycerides, as seen in fructose restriction and/or clinical KHK inhibition), as well as the fact that this association was not statistically significant among only white participants, complicates interpretation and application of the data.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants

et al. 2021

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Essential fructosuria (EF) is a benign, asymptomatic, autosomal recessive condition caused by loss-of-function variants in the ketohexokinase gene and characterized by intermittent appearance of fructose in the urine. Despite a basic understanding of the genetic and molecular basis of EF, relatively little is known about the long-term clinical consequences of ketohexokinase gene variants. We examined the frequency of ketohexokinase variants in the UK Biobank sample and compared the cardiometabolic profiles of groups of individuals with and without these variants alone or in combination. Study cohorts consisted of groups of participants defined based on the presence of one or more of the five ketohexokinase gene variants tested for in the Affymetrix assays used by the UK Biobank. The rs2304681:G>A (p.Val49Ile) variant was present on more than one-third (36.8%) of chromosomes; other variant alleles were rare (<1%). No participants with the compound heterozygous genotype present in subjects exhibiting the EF phenotype in the literature (Gly40Arg/Ala43Thr) were identified. The rs2304681:G>A (p.Val49Ile), rs41288797 (p.Val188Met), and rs114353144 (p.Val264Ile) variants were more common in white versus non-white participants. Otherwise, few statistically or clinically significant differences were observed after adjustment for multiple comparisons. These findings reinforce the current understanding of EF as a rare, benign, autosomal recessive condition.

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Kidney and vascular function in adult patients with hereditary fructose intolerance

Cited by 10 publications

References 48 publications

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

Transferrin Isoforms, Old but New Biomarkers in Hereditary Fructose Intolerance

Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants

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