Abstract
PurposeWilson’s disease (WD) is an autosomal recessive disorder of ATP7B gene 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 faulty ATP7B gene should not exhibit symptoms of WD, but one in three heterozygotes has copper metabolism abnormalities. This study examined heterozygote ATP7B mutation carriers using TCS to assess any basal ganglia changes compared with healthy controls.MethodsHeterozygote 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.ResultsThe 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).ConclusionsSN 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.
Highlights
Wilson’s disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism that is caused by malfunction of a putative copper-transporting P-type ATPase, ATP7B
magnetic resonance (MR) changes were found in T2* sequences in 2 cases: in the first case, there was bilateral hypointensity in the globus pallidus (GP) and in the second case, there was bilateral hypointensity in the substantia nigra (SN)
It has become an additional diagnostic tool for idiopathic Parkinson’s disease (PD) as hyperechogenicity of the SN is observed in about 90% of patients in the very early clinical stages of PD [18]
Summary
Wilson’s disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism that is caused by malfunction of a putative copper-transporting P-type ATPase, ATP7B. Heterozygotic carriers of the ATP7B gene should not exhibit symptoms of the disease, but copper metabolism abnormalities have been noted, in a range from 20% of cases [14], with up to 28.6% having low ceruloplasmin, and 35% exhibiting low serum copper levels [15, 16]. Conventional MR techniques do not show any structural changes in the basal ganglia of heterozygotes; Neurol Sci (2020) 41:2605–2612 magnetic resonance spectroscopy (MRS) revealed changes in the GP and thalamus suggestive of neuronal energy impairment, gliosis and copper accumulation [17]
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