Diagnostic Challenges of LRP4 Antibody Testing in Myasthenia Gravis: A Case Series of Four LRP4 Positive Cases With Uncertain Diagnostic Significance

Myasthenia gravis is an autoimmune disorder characterized by muscle weakness due to impaired neuromuscular transmission. While antibodies against the acetylcholine receptor and muscle-specific kinase are commonly used for diagnosis, a subset of patients remains seronegative, necessitating alternative biomarkers. Low-density lipoprotein receptor-related Protein 4 antibodies have emerged as a potential diagnostic marker in seronegative myasthenia gravis cases. However, misleading positive results have obscured diagnosis and management. This study explores the clinical relevance of low-density lipoprotein receptor-related Protein 4 antibodies in myasthenia gravis through four patient case studies. Patients presenting with concern for myasthenia gravis underwent a comprehensive diagnostic evaluation, including antibody testing for acetylcholine receptor, muscle-specific kinase, and low-density lipoprotein receptor-related Protein 4. Volitional single-fiber electromyography was also performed. All tests were employed per standardized laboratory protocols. All four patients were initially evaluated for suspected myasthenia gravis; however, despite positive low-density lipoprotein receptor-related Protein 4 antibody results, comprehensive clinical and electrophysiological evaluation ultimately excluded the diagnosis of myasthenia gravis. These cases underscore the limitations of low-density lipoprotein receptor-related Protein 4 antibody testing.