Metabolism and energy requirements in pantothenate kinase-associated neurodegeneration

Abstract

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder of coenzyme A homeostasis caused by defects in the mitochondrial pantothenate kinase 2. Patients with PKAN present with a progressive neurological decline and brain iron accumulation, but general energy balance and nutrition status among these patients has not been reported. To determine if defects in PANK2 change basic energy metabolism in humans, we measured body composition, resting energy expenditure, dietary intake, and blood metabolites among 16 subjects with PKAN. Subjects had a broad range of disease severity but, despite the essential role of coenzyme A in energy metabolism, the subjects had remarkably normal body composition, dietary intake and energy metabolism compared to population normal values. We did observe increased resting energy expenditure associated with disease severity, suggesting increased energy needs later in the disease process, and elevated urinary mevalonate levels.