A case of sudden cardiac death in a patient with LPIN1 gene mutation

Mutations in the LPIN1 gene (# 605518) are associated with lipodystrophy, hypertriglyceridemia and insulin resistance. Beyond that mutations in the LPIN1 gene were reported to cause rhabdomyolysis (Zeharia et al., 2008). Recently LPIN1 gene mutations were described as a major cause for recurrent myoglobinuria and rhabdomyolysis in childhood (Michot et al., 2010). Deficiency of the gene product lipin-1 leads to impaired synthesis of phospholipids, accumulation of detrimental intermediates in cells and defective cell membranes. Rhabdomyolysis shows often an recurrent course of disease and a high mortality. Episodes were triggered predominantly by febrile illnesses, fastening or strenuous exercise. Further repression of lipin-1 is induced by inflammatory cytokines (TNF-α, IL-1β). Between episodes of rhabdomyolysis physical examination and laboratory tests are often in normal limits.

We report a 33-month old boy who died four weeks after an acute bout of myositis beginning during a febrile airway infection. The autopsy demonstrated an acute congestive heart failure as the cause of death. A dilated cardiomyopathy with partial thinning of the cardiac muscle indicated a pre-existing damage. Furthermore a minor preductal coarctation of the aorta, and signs for a peripheral neuropathy were found. All examined muscle tissues showed myopathic damages. After his death the results of the genetic testing detected compound heterozygous LPIN1-mutations. Cause of death in this case is likely a combination of cardiac failure with respiratory exhaustion as a result of the decompensated cardiomyopathy. This might be triggered by the foregoing bout of rhabdomyolysis during a febrile infection. Furthermore cardiac arrhythmia as cause of death can't be excluded as neuropathic changes has been found on autopsy.

As conclusion, we recommend in patients with LPIN1 gene mutations preventive measures like avoiding prolonged fasting periods as well as strenuous exercises. Cardiac examinations should be performed routinely also in asymptomatic siblings.