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We reported a middle-aged man who initially presented with anhidrosis for 20 years and subsequently developed severe orthostatic hypotension, gastrointestinal dysmotility, and urogenital dysfunction. Due to progressive symptom aggravation, he was hospitalized and underwent comprehensive clinical assessment, neurophysiological studies, autonomic function tests, and multidisciplinary team (MDT) evaluation. The final diagnosis was pure autonomic failure (PAF). This case describes in detail the patient's long diagnostic course, differential diagnostic reasoning, the pivotal role of MDT management, and individualized treatment strategies and outcomes. The report aims to enhance the understanding of primary autonomic disorders characterized by neurogenic orthostatic hypotension for physicians, emphasizing the importance of systematic etiological screening and multidisciplinary collaboration in rare disease diagnosis and management to reduce misdiagnosis and improve prognosis and quality of life.