Patients With Aldolase B Deficiency Are Characterized by Increased Intrahepatic Triglyceride Content

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 11; pp. 5056 - 5064
• Main Authors: Simons, Nynke, Debray, François-Guillaume, Schaper, Nicolaas C, Kooi, M Eline, Feskens, Edith J M, Hollak, Carla E M, Lindeboom, Lucas, Koek, Ger H, Bons, Judith A P, Lefeber, Dirk J, Hodson, Leanne, Schalkwijk, Casper G, Stehouwer, Coen D A, Cassiman, David, Brouwers, Martijn C G J
• Format: Journal Article Web Resource
• Language: English
• Published: Washington, DC Endocrine Society 01.11.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: 3-Hydroxybutyric Acid - blood; Adult; Blood Glucose - metabolism; Body Composition; Body Mass Index; Case-Control Studies; Clinics; Dextrose; Diet; Enzymes; Ethylenediaminetetraacetic acid; Fatty liver; Female; Fructose; Fructose Intolerance - diagnostic imaging; Fructose Intolerance - metabolism; Fructose-Bisphosphate Aldolase - deficiency; Genetics & genetic processes; Glucose; Glucose - metabolism; Génétique & processus génétiques; Humans; Inborn errors of metabolism; Intolerance; Lean body mass; Life sciences; Liver - diagnostic imaging; Liver - metabolism; Liver diseases; Magnetic Resonance Imaging; Magnetic resonance spectroscopy; Male; Metabolism; Metabolism, Inborn Errors - metabolism; Middle Aged; Nuclear magnetic resonance spectroscopy; Oxidation; Pathogenesis; Phosphates; Sciences du vivant; Transferrin; Transferrin - analysis; Triglycerides; Triglycerides - metabolism; Type 2 diabetes; Young Adult; Belgium; Netherlands; Germany
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2018-02795

Abstract Context There is an ongoing debate about whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglyceride (IHTG) content in mice deficient for aldolase B (aldo B−/−), the enzyme that converts fructose-1-phosphate to triose phosphates. Objective To translate these experimental findings to the human situation. Design Case-control study. Setting Outpatient clinic for inborn errors of metabolism. Patients or Other Participants Patients with hereditary fructose intolerance, a rare inborn error of metabolism caused by a defect in aldolase B (n = 15), and healthy persons matched for age, sex, and body mass index (BMI) (n =15). Main Outcome Measure IHTG content, assessed by proton magnetic resonance spectroscopy. Results IHTG content was higher in aldo B−/− patients than controls (2.5% vs 0.6%; P = 0.001) on a background of lean body mass (median BMI, 20.4 and 21.8 kg/m2, respectively). Glucose excursions during an oral glucose load were higher in aldo B−/− patients (P = 0.043). Hypoglycosylated transferrin, a surrogate marker for hepatic fructose-1-phosphate concentrations, was more abundant in aldo B−/− patients than in controls (P < 0.001). Finally, plasma β-hydroxybutyrate, a biomarker of hepatic β-oxidation, was lower in aldo B−/− patients than controls (P = 0.009). Conclusions This study extends previous experimental findings by demonstrating that aldolase B deficiency also results in IHTG accumulation in humans. It suggests that the accumulation of fructose-1-phosphate and impairment of β-oxidation are involved in the pathogenesis. Patients with aldolase B deficiency, a defect in fructose metabolism, are characterized by increased hepatic fat content and glucose intolerance compared with age-, sex-, and BMI-matched controls.