Management of an LCHADD Patient During Pregnancy and High Intensity Exercise

Abstract

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.

Higher dietary protein intake preserves lean body mass, lowers liver lipid deposition, and maintains metabolic control in participants with long‐chain fatty acid oxidation disorders

“…Nor do they improve the lethargy and exercise intolerance commonly experienced among patients with defects in FAOD. 1 As a result, patients often have a more sedentary lifestyle than similarly aged normal counterparts. 12 A relatively low protein intake could compound the loss of LBM that accompanies disuse atrophy, and aging sarcopenia contributing to the lethargy and exercise intolerance that patients with FAOD already experience.…”

“…Many patients with LC-FAOD report muscle pain and lethargy with exercise and can become increasingly more sedentary over time. 1,31 Disuse muscle atrophy would be expected to affect both LBM and the ability to maintain activities of daily living. We did not measure participant activity in this study, so we cannot report whether these differences in LBM between the diet groups was able to close the "activity gap" in TEE of participants with LC-FAODs compared to normal controls that we have previously hypothesized.…”

“…For patients with late-onset LC-FAOD, the most common presentation is episodic myopathy associated with illness, stress, or prolonged exercise. 1 However, the severity of these episodes may range from mild exercise intolerance to rhabdomyolysis. 2 Current dietary management for patients with a LC-FAOD emphasizes avoiding prolonged fasting, restricting dietary long-chain fatty acid (LCFA) intake, and supplementing with medium-chain triglycerides (MCT) at meals and before exercise.…”

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

“…Restricting the consumption of specific fatty acids has been trialled in several FAO disorders [112][113][114], aiming to reduce the build-up of potentially toxic intermediates [115]. In a similar fashion, ketogenic (keto) diets are designed to decrease the amount of long-chain fatty acids, reducing the burden on medium-chain and short-chain acyl-CoA dehydrogenases to limit the build-up of fatty acyl-CoA intermediates [116,117].…”

Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation Disorders

“…In addition to these dietary regimens, many FAOD patients are given carnitine supplementation to prevent secondary carnitine deficiency due to acylcarnitine secretion. While a few studies have demonstrated positive effects of MCT [78-80] there is most certainly a need for better therapeutic options. Unfortunately, a drug known as bezafibrate that showed promise in cell culture studies [81] was recently assessed in clinical trials and found to have no efficacy in patients with long-chain FAOD [82, 83].…”