Patients with aldolase B deficiency are characterized by an increased intrahepatic triglyceride content.

CONTEXT: There is an ongoing debate on whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglycerides (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 subjects 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 compared to controls (2.5% versus 0.6%, p=0.001), at a background of a 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 beta-hydroxybutyrate, a biomarker of hepatic beta-oxidation, was lower in aldo B-/- patients compared to 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 beta-oxidation are involved in the pathogenesis.