TY - JOUR

T1 - No effect of triheptanoin in patients with phosphofructokinase deficiency

AU - Raaschou-Pedersen, Daniel Emil

AU - Madsen, Karen Lindhardt

AU - Lokken, Nicoline

AU - Storgaard, Jesper Helbo

AU - Quinlivan, Ros

AU - Laforet, Pascal

AU - Lund, Allan

AU - Van Hall, Gerrit

AU - Vissing, John

AU - Orngreen, Mette

PY - 2022/4

Y1 - 2022/4

N2 - Phosphofructokinase deficiency (PFKD) is a rare disorder of glycogen metabolism. The lack of phosphofructokinase activity blocks the oxidative pathway from glucose and glycogen to pyruvate. Patients suffer from myopathy, exercise intolerance, and myoglobinuria. Currently, there is no specific treatment for PFKD. We hypothesized that 2 weeks treatment with triheptanoin could improve oxidative metabolism during exercise by bypassing the blocked pyruvate generation in PFKD. The study was a randomized, double-blind, placebo-controlled crossover study. Three genetically verified patients completed two treatment periods of 14 days each with triheptanoin (0.3-1 g x kg -1 x day -1 ) or placebo liquid. Primary outcomes were heart rate, fatty acid and total oxidation measured via stable isotope and indirect calorimetry methodology during submaximal exercise. Triheptanoin did not improve the primary outcome heart rate during submaximal exercise compared to placebo . Palmitate oxidation was increased during submaximal exercise in one patient but did not increase in the two other patients during triheptanoin treatment. Palmitate production and palmitate utilization increased during exercise and increased to a greater extent with triheptanoin treatment in all three patients. This study suggests that triheptanoin treatment has no effect on heart rate or exercise performance despite increased palmitate production and utilization in patients with PFKD. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

AB - Phosphofructokinase deficiency (PFKD) is a rare disorder of glycogen metabolism. The lack of phosphofructokinase activity blocks the oxidative pathway from glucose and glycogen to pyruvate. Patients suffer from myopathy, exercise intolerance, and myoglobinuria. Currently, there is no specific treatment for PFKD. We hypothesized that 2 weeks treatment with triheptanoin could improve oxidative metabolism during exercise by bypassing the blocked pyruvate generation in PFKD. The study was a randomized, double-blind, placebo-controlled crossover study. Three genetically verified patients completed two treatment periods of 14 days each with triheptanoin (0.3-1 g x kg -1 x day -1 ) or placebo liquid. Primary outcomes were heart rate, fatty acid and total oxidation measured via stable isotope and indirect calorimetry methodology during submaximal exercise. Triheptanoin did not improve the primary outcome heart rate during submaximal exercise compared to placebo . Palmitate oxidation was increased during submaximal exercise in one patient but did not increase in the two other patients during triheptanoin treatment. Palmitate production and palmitate utilization increased during exercise and increased to a greater extent with triheptanoin treatment in all three patients. This study suggests that triheptanoin treatment has no effect on heart rate or exercise performance despite increased palmitate production and utilization in patients with PFKD. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

KW - Metabolic Myopathies

KW - Phosphofructokinase deficiency

KW - Triheptanoin

KW - Glycogen storage disease

KW - fat and carbohydrate metabolism

KW - ACID OXIDATION DISORDERS

KW - EXERCISE INTENSITY

KW - SKELETAL-MUSCLE

KW - FAT

KW - METABOLISM

KW - DISEASE

U2 - 10.1016/j.nmd.2022.01.012

DO - 10.1016/j.nmd.2022.01.012

M3 - Journal article

C2 - 35241345

VL - 32

SP - 295

EP - 304

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

SN - 0960-8966

IS - 4

ER -