Study of the Correlation Between the Effort Test, With the Assessment of Peripheral Oxygen Consumption and Cardiac Output in Patients With Acute Rhabdomyolysis Related to a Hereditary Disease of Metabolism, and the Biochemical Flux on Myoblasts: Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses

Rhabdomyolysis is a poorly known symptom associated with the destruction of skeletal muscle cells. The diagnosis of rhabdomyolyses is carried when the dosage of muscle enzymes, in particular creatine phosphate kinase (KPC), is greater than 1000 U/L (normal < 160 U/L).

Rhabdomyolyses may be of viral origin, but fever and viruses are also triggers of genetic diseases. Also, the incidence of genetic rhabdomyolyses, representing 10 to 15% of all rhabdomyolyses, is underestimated. Genetic causes are heterogeneous. They are mainly attributed to hereditary diseases of metabolism, in particular fatty acid oxidation defects, Lipin-1 deficiency, muscle glycogenoses, TANGO2 deficiency, mitochondrial cytopathies and calcium channels anomalies of in particular RYR1.

Whatever the cause, traumatic, infectious or genetic, the rhabdomyolyses cause an alteration of the metabolism of adenosine triphosphate and a deregulation of the ionic channels, with the consequences of an intracytoplasmic calcium release and the destruction of muscle cells.

The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by fever and fasting. They are unpredictable. In spite of the care of patient in an intensive care unit, the occurrence of renal failure and heart rhythm disorders explains a significant acute-phase mortality rate. There is an urgent need to understand the pathophysiological mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to identify specific treatments.

The pathophysiological mechanism of rhabdomyolyses related to Lipin-1 deficiency has been identified. Two patients with Lipin-1 deficiency treated in vivo by Hydroxychloroquine (Plaquenil ®, 6 mg/kg/day by one oral intake) rapidly standardized their serum inflammatory profile and corrected their clinical phenotype: Plasma creatine phosphokinase levels, Amount of mitochondrial DNA in plasma, number of myolyses, muscular pain, quality of life. One of these two patients, suffering from cardiac dysfunction already reported in Lipin-1 deficiency (left ventricular ejection fraction or LVEF 45%), significantly and durably improved cardiac function after one month of treatment (LVEF 62%). In addition, his fatigability and sleep disturbances have dramatically improved.