Neutral lipid storage disease with myopathy: A family report

Objective: To study the clinical, myopathological features in neutral lipid storage disease with myopathy (NLSDM) caused by a novel PNPLA2 mutation. Methods: Two patients were siblings. The proband was a 40-year-old woman. She presented progressive limb weakness and muscle atrophy at 35 years old. Her 55-year-old brother presented deafness at 35 years old and limb weakness at 45 years old. He suffered from ventricular septal defect. Open biosies were performed on them and specimens were studied histologically enzymhistochemically, and ultrastructurally. All the exons of PNPLA2 gene were analyzed in the both patients and 3 healthy family individuals. Results: Muscle biopsy in both patients revealed hypertrophy and atrophy of fibers with proliferation of connective tissue. There were numerous lipid droplets and plenty of rimmed vacuoles in the fibers. Electron microscopy revealed lipid droplets between sarcomeres as well as myelin figures. A single homozygous base substitution was detected at the beginning of intron 2 (IVS2 + 1G > A) of PNPLA2 in two patients, but not in the healthy family individuals. Conclusion: The novel IVS2 + 1G > A mutation of PNPLA2 causes NLSDM with prominent limb weakness. The disease may be associated with auditory nerve lesions and congenital heart disease. Rimmed vacuoles with lipid storage in the fibers might have indication for diagnosis of NLSDM. © 2009 by the Chinese Medical Association.