LPIN1 Mutations are an Important Cause of Rhabdomyolysis

Case Study: Recurrent rhabdomyolysis in childhood is often caused by inborn errors of mitochondrial fatty acid oxidation, oxidative phosphorylation, and glycogenolysis. In 2008, autosomal recessive LPIN1 mutation was identified as an important cause of rhabdomyolysis. Most episodes occur before 5 years of age and are precipitated by febrile illness, physical activity, or fasting. Mortality is 30%. Between episodes, patients are asymptomatic or exhibit exercise-induced myalgias, creatine kinase (CK) levels are usually normal. Symptoms improve with increasing age. The LPIN1 gene encodes lipin-1, an enzyme in triglyceride and membrane phospholipid biosynthesis. Homozygote mutations lead to rhabdomyolysis, heterozygote mutations to statin-induced myopathy, and the pathophysiology remains unclear.

A 10-year-old boy was investigated for frequent myalgias, exercise intolerance, calf hypertrophy, and elevated CK levels of 1,500 U/L. His brother had died within 2 years due to an adenovirus infection. Mutation analysis for Becker muscular dystrophy was negative and a muscle biopsy unremarkable. Shortly after, the boy developed focal rhabdomyolysis of the lateral compartment of the leg after prolonged physical activity, with compartment syndrome and residual foot drop palsy. Evaluation of defects of mitochondrial fatty acid oxidation, oxidative phosphorylation, or glycogenolysis, repeat myoglobin in urine, a muscle MRI, and a forearm ischemia exercise test were negative. A large intragenic deletion in the LPIN1 gene was detected. Over the next years, the CK repeatedly rose to 8,000 U/L after exercise with no further episodes of rhabdomyolysis, but without improvement over time.

LPIN1 mutation is an important cause of focal and generalized rhabdomyolysis in childhood. The late manifestation, the absence of improvement, and the severe focal rhabdomyolysis are unusual in this patient. In retrospect, his brother had probably died from fulminant rhabdomyolysis during an infection. LPIN1 mutation is an important cause of rhabdomyolysis which should always be considered in unclear rhabdomyolysis in childhood.

Keywords: rhabdomyolysis, neuromuscular, LPIN1 mutation.