Screening of Wilson’s disease in a psychiatric population: difficulties and pitfalls. A preliminary study

Abstract

BackgroundWilson’s disease (WD) is a rare autosomal-recessive, inherited disorder caused by a mutation in the copper-transporting gene ATP7B affecting the liver and nervous system. About 30% of patients with WD may initially present with psychiatric symptoms, and diagnosis can be difficult to establish. The objectives of the present preliminary study were [1] to evaluate the relevance of serum copper (Cu) and ceruloplasmin (Cp) measures in hospitalized patients with psychiatric disorders; and [2] to identify possible mutations in the ATP7B gene in patients with abnormal biological copper profile.MethodsAll psychiatric patients who participated in this study were hospitalized in Saint-Jean de Dieu Hospital (Lyon, France). Cp was measured by immunoturbidimetry and serum Cu by inductively coupled plasma-optical emission spectrometry. When Cp and serum Cu levels were inferior to, respectively, 0.18 g/L and 0.88 mg/L in combination with atypical psychiatric presentations, complete clinical examinations were performed by multidisciplinary physicians specialized in WD. In addition, mutation detection in the ATP7B gene was performed.ResultsA total of 269 patients completed the study. (1) 51 cases (19%) showed both decreased Cp and Cu concentrations. (2) Molecular genetic tests were performed in 29 patients, and one ATP7B mutation (heterozygous state) was found in four patients. We identified three different missense mutations: p.His1069Gln, c.3207C>A (exon 14), p.Pro1379Ser, c.4135C>T (exon 21) and p.Thr1434Met, c.4301C>T (exon 21). No pathogenic mutation on either ATP7B allele was detected.ConclusionResults of Cp and/or serum Cu concentrations below the normal limits are common in patients with psychiatric disorders and nonrelevant and/or informative for the WD diagnosis. WD diagnosis is based on a combination of clinical and biological arguments. Psychiatric patients with suspicion of WD should be evaluated in a reference center. Trial registration CPP Lyon Sud-Est IVNo 10/044, CNIL No DR-2011-470, Afssaps No B100832-40 and CCTIRS No 10.612 bis, registered 8 June 2010

Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment

“…The determination of ceruloplasmin concentration has been proposed as an initial test for WD; however, it appeared to have low sensitivity as a sole assessment. 63 , 64 Currently, in cases of first psychiatric episode (especially in young adults), baseline liver tests, an interview including history of hepatic disorders, detailed family history (including liver, neurological and psychiatric disorders including WD), physical examination (including general, neurological and ophthalmological assessment) and brain magnetic resonance imaging are recommended in order to exclude WD before beginning psychiatric pharmacological treatment. 13 – 15 In cases with abnormal results, international WD diagnostic criteria such as the Ferenci score ( Table 2 ) should be used to confirm the WD diagnosis.…”

“…However, such procedures are not routine, and serum ceruloplasmin level, often performed as a single test, is not sufficiently sensitive. 12 , 63 , 64 …”

Serum ceruloplasmin-ferroxidase activity in bipolar disorder is elevated compared to major depressive disorder and schizophrenia: a controlled study

“…Many studies have shown that dysregulation of Cu adversely influences biological processes of several psychiatric disorders including SZ [21][22][23][24][25][26][27][28][29][30], BD [25,[31][32][33], and MD [25,28,34]. The reduced [28,30,35,36], elevated [21][22][23][26][27][28][29]37,38], and unaltered [25,28,39,40] Cu levels in SZ patients have been mentioned in different studies. Higher Cu concentrations were reported in the course of the BD [41].…”

“…Cp was indicated as a serum biomarker for drug-free MD patients [49]. Unchanged levels of Cp were reported in BD and MD [25]. Lower Cp levels were shown in MD [50].…”

Schizophrenia-like disorder in Wilson's disease

“…Такие пациенты нуждаются в исследовании обмена меди, уровня церулоплазмина в сыворотке крови, состояния печеночных функций. Считается, что уровни церулоплазмина ≤0,13 г/л и меди ≤0,60 мг/л являются наиболее точными показателями для выявления потенциальной БВ у психиатрических пациентов с нормальным печеночным и неврологическим профилями [21]. Немаловажными диагностическими критериями будут кольца Кайзера-Флейшера, наличие тремора, не связанного с применением антипсихотиков [14,19].…”