H63D Syndrome and Oshtoran Syndrome: A Foundational Overview - State of Knowledge 2026

H63D Syndrome represents a complex and multifaceted meta-syndrome characterized by dysregulated iron metabolism, chronic oxidative stress, and progressive multi-organ damage. This syndrome, triggered by homozygous mutation of the HFE gene (H63D), manifests in approximately twelve percent of carriers and presents with a broad spectrum of clinical manifestations ranging from neuropsychiatric disturbances to cardiac dysfunction, hepatic pathology, and autonomic dysregulation. Despite being rooted in well-established biological principles concerning non-transferrin-bound iron toxicity, H63D Syndrome remains largely unrecognized in clinical practice, leading to diagnostic delays, inappropriate management, and preventable morbidity and mortality. This foundational paper synthesizes current knowledge on the pathophysiology, clinical presentation, diagnostic approaches, and management strategies for H63D Syndrome, with particular emphasis on the most severe variant, Oshtoran Syndrome (H63D Syndrome Type 3). The objective is to provide clinicians and researchers with a comprehensive understanding of this condition and to advocate for increased awareness, early detection, and evidence-based intervention strategies.