Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation

Behrend, Annie M.; Harding, Cary O.; Shoemaker, James D.; Matern, Dietrich; Sahn, David J.; Elliot, Diane L.; Gillingham, Melanie B.

doi:10.1016/j.ymgme.2011.09.030

Cited by 48 publications

(41 citation statements)

References 19 publications

(19 reference statements)

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“…Combining MCTs with carbohydrates accelerates MCT oxidation without negatively affecting endogenous carbohydrate oxidation. The positive effect of MCT supplementation on exercise performance in long chain fatty acids disorders has been described before, but it remained unclear whether this effect was due to improved metabolic efficiency at the level of the heart, the skeletal muscle or both (Gillingham et al 2006;Behrend et al 2012).…”

Section: Discussionmentioning

confidence: 92%

“…A study in nine LCHADD patients showed a positive effect of MCT supplementation (0.5 g/kg lean body mass) on exercise tolerance (Gillingham et al 2006). A second study in 11 patients showed a lower steady state heart rate at the same workload after using pre-exercise MCT supplementation (0.5 g/kg lean body mass) compared to isocaloric carbohydrate supplementation in long chain fatty acid oxidation disorders (Behrend et al 2012). In addition, a positive effect of an odd chain triglyceride, triheptanoate, on exercise performance in a single LCHADD patient has been reported (Karall et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD, OMIM 600890) is a rare inborn error of long chain fatty acid metabolism, resulting in mitochondrial dysfunction with subsequent energy shortage as well as toxic effects of fatty acid metabolites (den Boer et al 2002). Clinically, this results in hypoketotic hypoglycaemia, metabolic acidosis, cardiomyopathy and liver disease presenting in infancy (den Boer et al 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Clinically, this results in hypoketotic hypoglycaemia, metabolic acidosis, cardiomyopathy and liver disease presenting in infancy (den Boer et al 2002). In those patients who survive early childhood, the main characteristics are fatigue and exercise intolerance, retinopathy and less common peripheral neuropathy (Spiekerkoetter 2010).…”

Section: Introductionmentioning

confidence: 99%

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Management of an LCHADD Patient During Pregnancy and High Intensity Exercise

et al. 2016

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In this report we describe a female Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) patient who suffered from severe exercise intolerance. At age 34, the patient became pregnant for the first time. After an uneventful first 32 weeks of pregnancy she developed sinus tachycardia (resting heart rate 120-134 bpm) and lactate and creatinine kinase levels increased (3.3 mmol/L and 264 U/L, respectively). Increasing MCT supplementation (dose and frequency of administration) lowered heart rate and improved biochemical parameters. At 34 weeks the heart rate rose again and it was decided to deliver the child by caesarean section. Postpartum both mother and child did well.Prior to pregnancy, she performed exercise tests with different doses of medium chain triglycerides (MCTs) to establish a safe and effective exercise program (baseline test, second test with 10 g MCTs and third test with 20 g of MCTs). In the MCT supplemented tests the maximal power output was 23% (second test) and 26% (third test) higher, while cardiac output at maximal power output was the same in all three tests (~15.8 L/min).In conclusion, this is the first report of pregnancy in an LCHADD patient, with favourable outcome for both mother and child. Moreover, in the same patient, MCT supplementation improved cardiac performance and metabolic parameters during high intensity exercise. Using impedance cardiography, we got a clear indication that this benefit was due to improved muscle energy generation at high intensity exercise, since at the same cardiac output a higher power output could be generated.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Management of an LCHADD Patient During Pregnancy and High Intensity Exercise

et al. 2016

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“…(b) Blood glucose concentration during the standard incremental cycle test -samples taken from earlobe (in mg/dL). Y-axis is blood glucose concentration in mg/dL oxidation of medium chain fats, decreased the oxidation of glucose, and lowered cardiac workload during exercise when compared with carbohydrate supplementation in eight LCHADD out of 11 FAOD patients (Behrend et al 2012). However, these reports did not focus on the anaerobic threshold during incremental or endurance physical exertion tests in these patients.…”

Section: Discussionmentioning

confidence: 99%

Sports in LCHAD Deficiency: Maximal Incremental and Endurance Exercise Tests in a 13-Year-Old Patient with Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency (LCHADD) and Heptanoate Treatment

Mair¹,

Albrecht

Niedermayr

et al. 2014

JIMD Reports

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Exercise and subsequent catabolism is a potential trigger for creatine kinase (CK) concentration increase (rhabdomyolysis) in patients with LCHADD, therefore we evaluated the clinical and biochemical stability under physical exertion conditions at the age of 13 years in a currently 14-year-old LCHADD patient treated with heptanoate.LCHADD was diagnosed during first decompensation at age 20 months. In the following 2 years, the patient had several episodes of rhabdomyolysis. Heptanoate 0.5-1 g/kg/day was started at 4 years, with no further CK elevations since. He is clinically stable, has retinopathy without vision impairment or polyneuropathy. Maximal incremental and endurance exercise tests were performed to evaluate both clinical and metabolic stability during and after exertion.Physical fitness was adequate for age (maximum blood lactate 7.0 mmol/L, appropriate lactate performance curve, maximum heart rate of 196 bpm, maximum power 139 Watt = 2.68 Watt/kg body weight). There were no signs of clinical (muscle pain, dark urine) or metabolic derangement (stable CK, acyl carnitine profiles, blood gas analyses) - neither after maximal incremental nor endurance exertion.This case illustrates that both under maximal incremental and endurance exertion, clinical and biochemical parameters remained stable in this currently 14-year-old LCHADD patient receiving heptanoate treatment.

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Understanding the role of OXPHOS dysfunction in the pathogenesis of ECHS1 deficiency

Burgin

McKenzie

2020

FEBS Letters

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Mitochondria provide the main source of energy for eukaryotic cells, oxidizing fatty acids and sugars to generate ATP. Mitochondrial fatty acid β‐oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two key pathways involved in this process. Disruption of FAO can cause human disease, with patients commonly presenting with liver failure, hypoketotic glycaemia and rhabdomyolysis. However, patients with deficiencies in the FAO enzyme short‐chain enoyl‐CoA hydratase 1 (ECHS1) are typically diagnosed with Leigh syndrome, a lethal form of subacute necrotizing encephalomyelopathy that is normally associated with OXPHOS dysfunction. Furthermore, some ECHS1‐deficient patients also exhibit secondary OXPHOS defects. This sequela of FAO disorders has long been thought to be caused by the accumulation of inhibitory fatty acid intermediates. However, new evidence suggests that the mechanisms involved are more complex, and that disruption of OXPHOS protein complex biogenesis and/or stability is also involved. In this review, we examine the clinical, biochemical and genetic features of all ECHS1‐deficient patients described to date. In particular, we consider the secondary OXPHOS defects associated with ECHS1 deficiency and discuss their possible contribution to disease pathogenesis.

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Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation

Cited by 48 publications

References 19 publications

Management of an LCHADD Patient During Pregnancy and High Intensity Exercise

Management of an LCHADD Patient During Pregnancy and High Intensity Exercise

Sports in LCHAD Deficiency: Maximal Incremental and Endurance Exercise Tests in a 13-Year-Old Patient with Long-Chain 3-Hydroxy Acyl-CoA Dehydrogenase Deficiency (LCHADD) and Heptanoate Treatment

Understanding the role of OXPHOS dysfunction in the pathogenesis of ECHS1 deficiency

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