Neutral lipid storage disease with myopathy: clinicopathological and genetic features of nine Iranian patients

Abstract

The rare disorder known as Neutral Lipid Storage Disease with Myopathy presents with a variety of clinical manifestations, including myopathy, cardiac dysfunction, and other organ complications. Early diagnosis is crucial due to the increased risk of cardiomyopathy. We describe the clinical, histopathological, muscle imaging, and genetic findings of nine neutral lipid storage myopathy patients. Proximal weakness and asymmetric involvement may suggest lipid storage myopathy. While skeletal muscle weakness was the main manifestation in our patients, one case presented only with hyperCKemia. Additionally, three patients had fertility issues, two suffered from diabetes mellitus, two had cardiomyopathy, and one had a history of hypothyroidism. Muscle histopathology revealed lipid depositions and rimmed vacuoles, prompting peripheral blood smears to detect Jordan Anomalies. All muscle biopsies and peripheral blood smear showed lipid droplets, rimmed vacuoles, and Jordan anomaly. Identifying PNPLA2 gene mutations is important for diagnosing neutral lipid storage myopathy; our cases showed some novel mutations. This study highlights the importance of early diagnosis and comprehensive evaluation in managing neutral lipid storage myopathy cases.

Keywords: Cardiomyopathy; Jordan anomaly; NLSDM; Neutral lipid storage disease with myopathy; Patatin-like phospholipase domain-containing 2; Rimmed vacuole; Skeletal myopathy.