(Kiosk 3) A Severe Presentation of Double Seronegative, anti-lrp4 Mediated Myasthenia Gravis

Case Diagnosis: This case report discusses a patient with new diagnosis of double seronegative, anti-low density lipoprotein receptor-related protein-4 (LRP4) positive Myasthenia Gravis (LAPMG).

Case Description or Program Description: We present a devastating case of a 74-year-old male with past medical history of hypertension, hyperlipidemia, and coronary artery disease who admitted to the intensive care unit for progressive failure to thrive and encephalopathy due to severe hypercapnic, hypoxic respiratory failure.

Setting: University-based teaching hospital

Assessment/Results: During this hospitalization, extensive work-up did not reveal central nervous system, infectious, or paraneoplastic disease. Inflammatory markers were within normal limits. Electromyography (EMG) showed neuro-transmissional disorder involving the post-presynaptic membrane at the neuromuscular junction. Anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibodies were negative. Anti-LRP4 antibody was detected.

Discussion (relevance): By the time this patient sought medical care, he was debilitated by advanced stages of this disease. During his hospital course, the initial differential diagnosis was broad, yet was concerning for neuromuscular pathology. Although EMG was suggestive of MG, abnormal repetitive nerve stimulation in the setting of a patient with encephalopathy and generalized weakness can bear low specificity in the diagnosis. Laboratory testing confirmed the diagnosis of LAPMG, however effective medical treatment was not initiated due to laboratory processing times which later demonstrated LRP4 positivity. Unfortunately, the patient suffered further disease progression and ultimately died due to disease-related complications.
Given our need to better characterize the prevalence and clinical presentation of LAPMG, this case presentation provides additional data on known reports of anti-LRP4-mediated MG.

Conclusions: In conclusion, we need more to elucidate the clinical characteristics of LAPMG. We aim to raise awareness of this MG variant and advocate for early suspicion, diagnosis, and treatment for all variants of MG.