high intensity exercise in children with mcadd

Conditions: Medium Chain Acyl CoA Dehydrogenase Deficiency

Summary: medium-chain acyl-coa dehydrogenase deficiency (mcadd) is a rare genetic disorder affecting the body's ability to break down certain fats (β-oxidation) for energy, leading to symptoms like hypoketotic hypoglycaemia, jaundice, cardiomyopathy and seizures. responsible for the dehydrogenation step of fatty acids with chain lengths between 6 and 12 carbons as they undergo beta-oxidation in the mitochondria. deficiency in mcad can result in energy deficiency, the accumulation of acylcarnitine's and low serum carnitine concentrations. the primary objective of the pilot study is to analyse the effects of high-intensity exercise (cardiopulmonary exercise testing (cpet) \& high intensity circuit exercises ) on metabolic parameters and safety. this research is a pilot study comparing four patients with mcadd to four control subjects with the same characteristics. blood samples are collected for analysis of substrate utilization.

the primary objective of the study is to analyse the effects of high-intensity exercise (cpet \& high intensity circuit exercises) on metabolic parameters and safety. since exercise is tested approximately two hours after a meal, we expect few symptoms, as fat metabolism is only minimally engaged at this intensity. of interest could be the recovery from exercise, as fat metabolism is presumably activated during this phase. each mcadd-patient will attend two experimental visits. on the day of the first visit, the patient will arrive at uz gent after 1.5-hours following the meal. after 30 minutes, they will perform a cardiopulmonary exercise test (cpet) on a cycle ergometer. the standard cpet protocol that will be used is as follows: first, three minutes of cycling at a constant load (body weight (kg) / 2) in watts), followed by a maximal exercise test (ramp protocol: (body weight (kg) / 4) in watts per minute). during the cycling test, gas exchange (spirometry) is measured, and an ecg is taken. if no symptoms are observed, the patient may return home. on the second test day, two hours before the test, a breakfast will be consumed. 1.5-hours following the meal, the patient will arrive at uz gent, where a heart monitor will be placed, and an intravenous line will be inserted. following this, the patient will undergo a high-intensity exercise circuit. blood samples will be taken before and after the exercise at various intervals: immediately, after 30 minutes, 1 hour, and 1.5-hours. also, rer will be determined at each timepoint using indirect calorimetry. if no symptoms appear, the patient may return home. the patient will report symptoms for the 48 hours following the test. in the blood samples, measures of substrate utilization will be monitored: glucose, lactate, acylcarnitine levels, free fatty acids (ffa). also a marker of muscle damage will be assessed (creatine kinase). additional measures include: anthropometric measurements, including weight and height, physical activity through the children physical activity questionnaire).

Eligibility criteria:
inclusion criteria: * 8-17y old * control subjects matched by sex, age, and self reported tanner stage. * all children: height and weight between p5-p95 exclusion criteria: * no daily medication use * no conditions other than mcadd that restrict sports participation or physiology (e.g., no heart diseases, diabetes). * \ p95 on the height-weight curve * no neuromotor developmental delay (e.g., delayed achievement of motor milestones) * no recent immobilization (\<6 months) * no surgeries involving the musculoskeletal system

Keywords: mcadd cpet high intensity exercise acylcarnitine