Non-alcoholic fatty liver in hereditary fructose intolerance

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2 . The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-Lhomocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients.

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

“…Another altered pathway affected by F1P accumulation is fatty acid metabolism. Elevated F1P and subsequent activation of adenosine monophosphate (AMP) deaminase followed by inhibition of AMP-activated kinase (AMPK) leads to reduced β-oxidation of fatty acids and accumulation of triglycerides in the liver [ 28 , 29 ]. Furthermore, F1P also impacts glycosylation since it is a competitive inhibitor of liver MPI, which is critical for the N-glycosylation pathway [ 30 ].…”

“…Both hepatic and renal function are affected by ALDOB deficiency. Because of increased accumulation of triglycerides in the liver, HFI patients show a higher prevalence of fatty liver not linked to obesity or insulin resistance [ 29 ]. Pertaining to kidney function, rapid ATP consumption by renal cells to mitigate the lack of downstream metabolites produced by ALDOB leads to depletion of inorganic phosphate and ATP [ 25 , 42 ].…”

Transferrin Isoforms, Old but New Biomarkers in Hereditary Fructose Intolerance

“…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].…”

Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance

“…Besides, 93.8% had sonographic signs of liver steatosis at the end of follow-up. Recently it was suggested that non-alcoholic fatty liver disease (NAFLD) unrelated to obesity is highly prevalent in HFI patients [13]. Previously, Odievre et al considered steatosis as a side effect of long-term strict avoidance of fructose due to an unbalanced diet containing an excess of fat [14].…”