Neurogenic orthostatic hypotension as a rare presentation of Waldenström macroglobulinemia associated with light-chain amyloidosis: A diagnostic challenge

Neurogenic orthostatic hypotension (nOH) is frequently associated with synucleinopathies like pure autonomic failure (PAF). However, systemic diseases may mimic this presentation, posing a diagnostic challenge. We report a patient with isolated nOH initially suggestive of PAF. Detailed work-up revealed Waldenström macroglobulinemia with associated AL amyloidosis (WM-AL), affecting isolated postganglionic autonomic fibers but without classic systemic organ involvement. This case underscores the importance of considering secondary causes in patients with isolated autonomic dysfunction. Unlike idiopathic PAF, paraproteinemic neuropathies such as WM-AL require distinct diagnostic and therapeutic approaches. WM-AL can mimic primary autonomic disorders like PAF and should be included in the differential diagnosis of nOH, even in the absence of systemic manifestations.