Cardiac function and exercise adaptation in 8 children with LPIN1 mutations.

Area of Science:

• Cardiology
• Genetics
• Metabolic Disorders

Background:

• Lipin-1 deficiency is a primary cause of rhabdomyolysis, often triggered by fever, with a high mortality rate from cardiac arrest.
• Most patients with lipin-1 deficiency are clinically normal between acute rhabdomyolysis episodes.

Purpose of the Study:

• To investigate cardiac and exercise parameters in children with lipin-1 deficiency outside of acute rhabdomyolysis episodes.
• To assess the impact of fever on exercise response in lipin-1 deficiency.

Main Methods:

• Cardiac and exercise examinations (echocardiography, cycle ramp exercise) were performed on 8 children with LPIN1 mutations.
• Cardiac magnetic resonance spectroscopy was used in four patients.
• One patient underwent exercise testing during fever and normothermia.

Main Results:

• Most patients had normal resting cardiac function; one showed slight left ventricular dysfunction and impaired stroke volume response during exercise.
• Two patients exhibited impaired peripheral muscle adaptation during exercise, with an abnormal increase in cardiac output relative to oxygen uptake (dQ/dVO2).
• One febrile patient showed altered muscle reoxygenation and increased dQ/dVO2 compared to normothermia. Four patients had intracardiac steatosis.

Conclusions:

• Lipin-1 deficiency can lead to abnormal hemodynamic responses during exercise, suggesting impaired muscle oxidative phosphorylation.
• Fever exacerbates exercise abnormalities in lipin-1 deficiency.
• Intracardiac lipid accumulation may contribute to cardiac dysfunction in these patients.