Impaired ketogenesis in patients with adult-type citrullinemia

Abstract

Background/Aims: To clarify the mechanism causing fatty liver in adult-type citrullinemia, the effect of fasting on blood levels of free fatty acids, triglycerides, and ketone bodies was investigated in two cases. Methods: Blood and urine samples were collected from two patients and healthy volunteers 12, 15, 17, 21.5, and 24 hours after their last meal. Results: During 24-hour fasting free fatty acid concentrations increased in both cases to the concentrations found in the healthy volunteers. The levels of blood ketone bodies (β-hydoxybutyrate and acetoacetate) were markedly suppressed throughout the fasting test without any increase in urinary excretion of ketone bodies or organic acids in both cases when plasma citrulline concentrations were more than 10-fold higher than in controls. Serum triglyceride concentrations in case 1 paradoxically increased from 185 mg/dL to 294 mg/dL during 24-hour fasting when the citrulline concentration was extremely high. When hemodialysis was performed and plasma citrulline consequently decreased to near the normal level in case 1, levels of both serum triglycerides and blood ketone bodies responded normally to 24-hour fasting. Conclusions: These data suggest that ketogenesis was impaired in adult-type citrullinemia.