Transcranial sonography changes in heterozygotic carriers of the ATP7B gene

Abstract

Purpose Wilson's disease (WD) is an autosomal recessive disorder ofATP7Bgene leading to impaired copper metabolism. Brain imaging, such as magnetic resonance (MR) and transcranial sonography (TCS) in WD patients, shows changes mostly in the basal ganglia. Heterozygotic carriers of one faultyATP7Bgene should not exhibit symptoms of WD, but one in three heterozygotes has copper metabolism abnormalities. This study examined heterozygoteATP7Bmutation carriers using TCS to assess any basal ganglia changes compared with healthy controls. Methods Heterozygote carriers and healthy volunteers underwent the same standard MR and TCS imaging protocols. Heterozygotes were followed for 5 years and monitored for the development of neurological symptoms. Results The study assessed 34 heterozygotes (21 women), with mean age of 43 years (range of 18 to 74 years) and 18 healthy controls (13 women), with mean age of 47 years (range of 20 to 73 years). Bilateral lenticular nucleus (LN) hyperechogenicity was found in 25 heterozygotes, but none of the controls (p < 0.001). Bilateral substantia nigra (SN) hyperechogenicity was found in 8 heterozygotes and one control; another 3 heterozygotes had unilateral SN hyperechogenicity (p = 0.039 for the right;p = 0.176 for the left). Heterozygotes had larger SN area on both sides compared with controls (p = 0.005 right;p = 0.008 left). Conclusions SN and LN hyperechogenicity were more frequent in heterozygotes than in controls, probably due to copper accumulation, but it remains unknown if this predisposes to brain neurodegeneration.