Mitochondrial hepatopathy: Anticipated difficulties in management of fatty acid oxidation defects and urea cycle defects

Abstract

Fatty acid oxidation defects (FAOD) and urea cycle defects (UCD) are among the most common metabolic liver diseases. Management of these disorders is dotted with challenges as the strategies differ based on the type and severity of the defect. In those with FAOD the cornerstone of management is avoiding hypoglycemia which in turn prevents the triggering of fatty acid oxidation. In this review, we discuss the role of carnitine supplementation, dietary interventions, newer therapies like triheptanoin, long-term treatment and approach to positive newborn screening. In UCD the general goal is to avoid excessive protein intake and indigenous protein breakdown. However, one size does not fit all and striking the right balance between avoiding hyperammonemia and preventing deficiencies of essential nutrients is a formidable task. Practical issues during the acute presentation including differential diagnosis of hyperammonemia, dietary dilemmas, the role of liver transplantation, management of the asymptomatic individual and monitoring are described in detail. A multi-disciplinary team consisting of hepatologists, metabolic specialists and dieticians is required for optimum management and improvement in quality of life for these patients.

Keywords: Mitochondrial hepatopathy; Metabolic liver disease; Liver transplantation; Hyperammonemia; Hypoglycemia; Carnitine

Core Tip: Management of fatty acid oxidation defects and urea cycles defects has to be tailored to specific types of defects. Although dietary intervention remains the most important pillar of successful outcome, role of definitive and potential medications is assuming renewed significance. Management is challenging due to variations in type and severity of the enzyme defect.