Cardiac function and exercise adaptation in 8 children with LPIN1 mutations

Introduction: Lipin-1 deficiency is a major cause of rhabdomyolysis that are precipitated by febrile illness. The prognosis is poor, with one-third of patients dying from cardiac arrest during a crisis episode. Apart from acute rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac ultrasound parameters. Patients and methods: We report cardiac and exercise examinations of 8 children carrying two LPIN1 mutations. The examinations were performed outside of a myolysis episode, but one patient presented with fever during one examination. Results: All but one patient displayed normal resting cardiac function, as determined by echocardiography. One patient exhibited slight left ventricular dysfunction at rest and a lack of increased stroke volume during cycle ramp exercise. During exercise, peripheral muscle adaptation was impaired in 2 patients compared to healthy controls: they presented an abnormal increase in cardiac output relative to oxygen uptake: dQ/dVO(2) = 8.2 and 9.5 (> 2DS of controls population). One patient underwent 2 exercise tests; during one test, the patient was febrile, leading to acute rhabdomyolysis in the following hours. He exhibited changes in recovery muscle re oxygenation parameters and an increased dQ/dVO(2) during exercise compared with that under normothermia (7.9 vs 6), which did not lead to acute rhabdomyolysis. The four patients assessed by cardiac H-1-magnetic resonance spectroscopy exhibited signs of intracardiac steatosis. Conclusion: We observed abnormal haemodynamic profiles during exercise in 3/8 patients with lipin-1 deficiency, suggesting impaired muscle oxidative phosphorylation during exercise. Fever appeared to be an aggravating factor. One patient exhibited moderate cardiac dysfunction, which was possibly related to intracardiac stored lipid toxicity.