B-Mode TCS Detection of NTBI in the Substantia Nigra: First Report in a 40-Year-Old Patient with Genetically Confirmed H63D Syndrome

H63D syndrome is a distinct, genetically determined multisystem disorder occurring in three clinical types (Type 1 “Oslo syndrome,” Type 2, and Type 3 “Oshtoran syndrome”) and must be clearly distinguished from hereditary haemochromatosis. While homozygous HFE-H63D mutation carries only a minimal risk for classical haemochromatosis (2–3 %), approximately 10 % of homozygotes develop clinically relevant H63D syndrome. Pathophysiology resembles Wilson’s disease more than haemochromatosis, with persistent hypotransferrinaemia, chronically elevated transferrin saturation, and low ferritin promoting the accumulation of toxic non-transferrin-bound iron (NTBI). We report the case of a 40-year-old male patient with genetically confirmed H63D syndrome Type 1, no signs of Parkinson’s disease, and an age deliberately below the standard screening threshold for substantia nigra hyperechogenicity. High-resolution B-Mode transcranial sonography (transtemporal approach) revealed marked, homogeneous hyperechogenicity of the substantia nigra, loss of visual contrast with surrounding mesencephalic structures, and preserved structural integrity, bilaterally. Ferritin deposition and structural lesions were excluded, leaving NTBI deposition as the only plausible explanation. This represents the first in vivo visualization of NTBI in the substantia nigra in a patient under 45 years of age. B-Mode TCS may serve as a valid non-invasive tool for NTBI detection, offering potential for early diagnosis and follow-up in H63D syndrome before irreversible nigrostriatal damage occurs. Recognition that H63D homozygosity has distinct clinical implications beyond haemochromatosis is essential for timely diagnosis and intervention.<br>