Challenges and dilemmas in pediatric hepatic Wilson’s disease

Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q.This leads to copper deposition in various organs,most importantly in the liver and brain.The genetic mutations are vast,well reported in the West but poorly documented in developing countries.Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians.Diagnostic scoring systems are not fool-proof.The availability and affordability of chelators in developing countries impact the drug compliance of patients.While D-penicillamine is a potent drug,its side effects lead to drug discontinuation.Trientine is cost-prohibitive in developing countries.There is no single test to assess the adequacy of chelation.Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool.In the presence of cirrhosis,hypersplenism clouds the assessment of myelosuppression of drugs.Similarly,it may be difficult to distinguish disease tubulopathy from druginduced glomerulonephritis.Neurological worsening due to chelators may appear similar to disease progression.Presentation as fulminant hepatic failure requires rapid workup.There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices.This review addresses the challenges and clinical dilemmas faced at beside in developing countries.

肝豆灵片对痰瘀互结型Wilson病肝硬化预后的影响

目的:探讨肝豆灵片对痰瘀互结型Wilson病肝硬化预后的影响。方法:选择2020年4月至2021年4月住院的106例痰瘀互结型Wilson病肝硬化患者为研究对象,按照是否服用肝豆灵片分为观察组和对照组,对两组患者定期随访2年,随访期结束后计算两组患者生存率,选择Kaplan-Meier法绘制两组患者生存曲线,运用log-rank检验进行比较。根据患者生存结局,采用Cox回归分析Wilson病肝硬化预后的危险因素。结果:生存分析显示观察组患者2年生存率高于对照组(P<0.05),进一步分析显示在Child-Pugh分级为A级和B级患者中,两组患者生存率差异有统计学意义(P<0.05),C级中两组患者生存率差异无统计学意义(P>0.05)。Cox回归分析显示病程、脾切除、Child-Pugh评分和肝豆灵片是影响Wilson病肝硬化预后的独立危险因素(P<0.05)。结论:痰瘀互结型Wilson病肝硬化患者出现病程长、脾脏切除、Child-Pugh评分高、未服用肝豆灵片者其预后较差。肝豆灵片能提高痰瘀互结型Wilson病肝硬化患者生存率,但这种保护作用局限在Child-Pugh A级和B级患者。

不同中医证型Wilson病患者肝脏纤维化差异及其与弹性硬度值的关系

目的:探讨不同中医证型Wilson病(WD)患者肝脏硬度值(LSM)及纤维化指标差异及两者的关系。方法:回顾性收集2021年2月至2023年4月住院确诊的110例WD患者的临床资料,中医证型采用指标聚类分析,绘制聚类图。采用简单对应分析中医证型与ADL分级的相关性。比较不同中医证型的一般临床资料、LSM及肝纤维化相关指标,从而探讨LSM与肝纤维化及中医证型分布的关系。结果:WD患者中医证型以湿热内蕴证(59例,53.64%)居多,痰瘀互结证(43例,39.09%)次之,肝肾阴虚证(5例,4.54%)、脾肾阳虚证(3例,2.73%)较少;痰瘀互结证偏向0~Ⅰ级,湿热内蕴证偏向Ⅱ级,肝肾阴虚证偏向Ⅲ~Ⅳ级,脾肾阳虚证在二维投影图中间,并未偏向WD病变程度某一分级;痰瘀互结证、肝肾阴虚证、脾肾阳虚证患者肝脏LSM均高于湿热内蕴证(P<0.05);肝肾阴虚证、脾肾阳虚证患者血清透明质酸(HA)和Ⅳ型胶原(Ⅳ-C)水平高于湿热内蕴证、痰瘀互结证组(P<0.05),4组患者Ⅲ型前胶原氨基端肽(PⅢNP)、层黏连蛋白(LN)水平差异无统计学意义(P>0.05)。湿热内蕴证、痰瘀互结证、肝肾阴虚证中LSM与HA、Ⅳ-C均呈不同程度的正相关。结论:LSM联合血清学指标能更好地评估不同证型WD患者肝纤维化程度。

抑郁倾向Wilson病患者的注意偏向特征及与反刍思维的关系研究

目的 探究抑郁倾向Wilson病(WD)患者的注意偏向特征及与反刍思维的关系。方法 招募2022年1月至2023年1月安徽中医药大学神经病学研究所附属医院收治的WD患者51例,根据贝克抑郁量表(BDI)评分将其分为抑郁组(≥5分,30例)和非抑郁组(≤4分,21例)。比较两组反刍思维量表(RRS)评分及情绪Stroop范式试验结果,并分析观察指标间的关联性。结果 抑郁组在RRS的症状反刍、反省深思、强迫思考维度得分及总分均高于非抑郁组,差异有统计学意义(P<0.05)。抑郁组对负性词的反应时间显著慢于非抑郁组(P<0.05);两组对中性词及正性词的反应时间比较差异无统计学意义(P>0.05)。WD患者对负性词反应时间与BDI评分、RRS总分、RRS的症状反刍维度得分呈正相关(P<0.05),对正性词和中性词反应时间与BDI评分、RRS总分及RRS各维度得分的相关性不显著(P>0.05)。多因素线性回归分析结果显示,BDI评分、RRS总分、RRS的症状反刍维度得分是WD患者对负性词反应时间的影响因素(P<0.05)。结论 抑郁倾向WD患者会过多关注负性情绪信息,反刍思维可能是导致抑郁倾向WD患者负性情绪注意偏向的原因之一。

Wilson's disease:Revisiting an old friend

Wilson's disease(WD)is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs,such as the central nervous system.It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter.This protein facilitates the incorporation of copper into ceruloplasmin.More than 800 mutations associated with WD have been described.The onset of the disease frequently includes manifestations related to the liver(as chronic liver disease or acute liver failure)and neurological symptoms,although it can sometimes be asymptomatic.Despite it being more frequent in young people,WD has been described in all life stages.Due to its fatal prognosis,WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms.The diagnosis is established with a combination of clinical signs and tests,including the measurement of ceruloplasmin,urinary copper excretion,copper quantification in liver biopsy,or genetic assessment.The pharmacological therapies include chelating drugs,such as D-penicillamine or trientine,and zinc salts,which are able to change the natural history of the disease,increasing the survival of these patients.In some cases of end-stage liver disease or acute liver failure,liver transplantation must be an option to increase survival.In this narrative review,we offer an overview of WD,focusing on the importance of clinical suspicion,the correct diagnosis,and treatment.

Clinical Efficacy and Safety of Chelation Treatment with Typical Penicillamine in Cross Combination with DMPS Repeatedly for Wilson's Disease

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine （PCA） in cross combination with sodium 2, 3-dimercapto-l-propane sulfonate （DMPS） repeatedly in patients with Wilson＇s disease （WD）. Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocy- topenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Im- proved or recovered liver fimction in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up pe- riod of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maitain lifelong therapy.

Diagnostic challenges of Wilson’s disease presenting as acute pancreatitis, cholangitis, and jaundice

Wilson’s disease is a rare disorder of copper transport in hepatic cells,and may present as cholestatic liver disease;pancreatitis and cholangitis are rarely associated with Wilsons’s disease.Moreover,cases of Wilson s disease presenting as pigmented gallstone pancreatitis have not been reported in the literature.In the present report,we describe a case of a 37-year-old man who was admitted with jaundice and abdomina pain.The patient was diagnosed with acute pancreatitis,cholangitis,and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography.However,because of his long-term jaundice and the presence of pigmented gallstones,the patient underwent further evaluation for Wilson’s disease,which was subsequently confirmed.This patient’s unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson’s disease and cholestasis,and the difficulties associated with their differentiation.It suggests thatWilson’s disease should be considered in patients with pancreatitis,cholangitis,and severe protracted jaundice caused by pigmented gallstones.

Clinically diagnosed late-onset fulminant Wilson's disease without cirrhosis: A case report

A 64-year-old woman was referred to our hospital with jaundice of the bulbar conjunctiva and general fatigue. After admission, she developed hepatic encephalopathy and was diagnosed with fulminant hepatitis based on the American Association for the Study of Liver Disease(AASLD) position paper. Afterwards, additional laboratory findings revealed that serum ceruloplasmin levels were reduced, urinary copper levels were greatly elevated and Wilson's disease(WD)-specific routine tests were positive, but the Kayser-Fleischer ring was not clear. Based on the AASLD practice guidelines for the diagnosis and treatment of WD, the patient was ultimately diagnosed with fulminant WD. Then, administration of penicillamine and zinc acetate was initiated; however, the patient unfortunately died from acute pneumonia on the 28 th day of hospitalization. At autopsy, the liver did not show a bridging pattern of fibrosis suggestive of chronic liver injury. Here, we present the case of a patient with clinically diagnosed late-onset fulminant WD without cirrhosis, who had positive disease-specific routine tests.

Hepatocellular carcinoma in a non-cirrhotic patient with Wilson's disease

We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis with fibrosis, but no cirrhosis. The disease was treated with D-penicillamine for 3 years until acute discomfort in the right upper quadrant led to detection of multifocal hepatocellular carcinoma, which was successfully resected. The histological examination confirmed the malignant nature of the 4 lesions, which were classified according to Edmondson and Steiner as poorly differentiated hepatocellular carcinoma grade 3. The non-tumoral parenchyma showed 80% steatosis with ballooned cells, lobular inflammation, septal fibrosis but no cirrhosis. Hepatocellular carcinoma is rare in Wilson's disease, especially in the absence of cirrhosis. The literature's 28 published cases are reviewed and the contributory role of copper in the hepatocarcinogenic process is discussed.

Genotype phenotype correlation in Wilson's disease within families-a report on four south Indian families

AIM: To study the genotype phenotype correlation in Wilson's disease (WD) patients within families. METHODS: We report four unrelated families from South India with nine members affected with WD. Phenotype was classified as per international consensus phenotypic classifi cation of WD. DNA was extracted from peripheral blood and 21 exons of ATP7B gene and flanking introns were amplified by polymerase chain reaction (PCR). The PCR products were screened for mutations and the aberrant products noted on screening were sequenced. RESULTS: Four separate ATP7B mutations were found in the four families. ATP7B mutations were identical amongst affected members within each family. Three families had homozygous mutations of ATP7B gene while one family had compound heterozygous mutation, of which only one mutation was identifi ed. We noted concordance between ATP7B gene mutation and Wilson's disease phenotype amongst members within each family. The age of onset of symptoms or of detection of asymptomatic disease, baseline serum ceruloplasmin and baseline urinary copper levels were also similar in affected members of each family. Minor differences in phenotype and baseline serum ceruloplasmin level were noted in one family.CONCLUSION: We report concordance between ATP7B mutation and WD phenotype within each family with > 1 member affected with WD. Homozygous ATP7B mutation was present in 3 of the 4 families studied. Our report supports allelic dominance as a determinant of WD phenotype. However, in one family with compound heterozygous mutation, there was a similar WD phenotype which suggests that there may be other factors determining the phenotype.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

The role of mTOR signaling pathway in regulating autophagy in liver injury of TX mice with Wilson’s disease

Wilson disease(WD),known as hepatolenticular degeneration(HLD),is a treatable autosomal recessive disorder of copper metabolism.Because copper deposits in the liver first,the liver is not only the original defective organ but also the most affected organ.The liver injury is also one of the main causes of death throughout the course of the disease.Therefore,the treatment of liver injury is the main task of WD treatment,which is of great significance to improve the prognosis of patients.Autophagy is a process that promotes cell survival through degradation,recycling,and absorption in order to maintain the normal physiological function of cells,while excessive autophagy can aggravate cell death.In view of the abnormal damage of liver cells in patients with WD,which may be related to the change of autophagy level,in this study,we established an animal model of WD through toxic milk(TX)mice,observed the change of autophagy level in the liver,and observed the change of liver damage in mice after treatment with autophagy inhibitors.It was found that the mTOR signaling pathway was activated and autophagy was inhibited in Wilson mouse liver.After treatment with rapamycin,the autophagy level of mice liver was upregulated,and the copper content of mice liver was reduced,and the damage was alleviated.TX mouse hepatocytes were isolated,after using siRNA to interfere with mTOR expression,the copper accumulation was significantly reduced,which was the same with RAPA treatment.The results showed that in TX mice,the damage caused by copper accumulation in the liver may be related to the decrease of autophagy level caused by the activation of the mTOR signaling pathway.Our findings suggested that RAPA or the use of siRNA targeting mTOR may have potential applications in the treatment of Wilson’s disease.

Liver transplantation in Wilson's disease: Single center experience from Saudi Arabia

AIM: To determine liver transplantation outcomes in Wilson's disease (WD) patients, focusing on neurological manifestations. METHODS: This retrospective study assessed data from 16 WD patients (nine males, 56%) who had liver transplants between 1991 and 2007. Survival, graft function, and neurological complications were assessed during a follow-up period of up to 15 years. In addition, each patient's medical record was reviewed in detail to find the type of Wilson's disease (hepatic or hepatic plus neurological WD), indication for liver transplantation, use of chelating agents prior to transplantation, immediate and long term complications following transplantation, the donor details, and the pathology of explanted liver. RESULTS: End-stage liver disease was the indication for transplantation in all 16 WD patients. Four patients displayed WD-related neurological symptoms in addition to liver disease. Living-related liver transplantation was done in three cases. One patient died on postoperative day 6 due to primary graft non-function. Oneyear post liver transplant survival was 94%. Neurological manifestations of all four patients disappeared during their follow-up. Four patients developed acute cellular rejection, but all responded to treatment. One patient developed chronic ductopenic rejection after 15 years post-transplantation and their graft failed; this patient is currently waiting for re-transplantation. Fourteen patients (88%) are still living. The long-term average survival is currently 10.5 years, with a current median survival of 8 years. Long-term graft survival is currently 81%. CONCLUSION: Shortand long-term survival in WD patient liver transplantation was excellent, and neurological and psychological WD manifestations disappeared during long-term follow-up.

Acute liver failure with hemolytic anemia in children with Wilson’s disease:Genotype-phenotype correlations?

BACKGROUND Wilson’s disease(WD)is a rare autosomal recessive inherited disorder of copper metabolism.Acute liver failure(ALF)and hemolytic anemia represent the most severe presentation of WD in children.No clear genotype-phenotype correlations exist in WD.Protein-truncating nonsense,frame-shift,or splice-site variants may be associated with more severe disease.In contrast,missense variants may be associated with late-onset,less severe disease,and more neurological manifestations.Recently,a gene variant(HSD17B13:TA,rs72613567)with a possible hepatic protective role against toxins was associated with a less severe hepatic phenotype in WD.AIM To analyze the possible genotype-phenotype correlations in children with WD presented with ALF and non-immune hemolytic anemia.METHODS The medical records of children with WD diagnosed and treated in our hospital from January 2006 to December 2020 were retrospectively analyzed.The clinical manifestations(ALF with non-immune hemolytic anemia or other less severe forms),laboratory parameters,copper metabolism,ATP7B variants,and the HSD17B13:TA(rs72613567)variant were reviewed to analyze the possible genotype-phenotype correlations.RESULTS We analyzed the data of 51 patients with WD,26 females(50.98%),with the mean age at the diagnosis of 12.36±3.74 years.ALF and Coombs-negative hemolytic anemia was present in 8 children(15.67%),all adolescent girls.The Kayser-Fleisher ring was present in 9 children(17.65%).The most frequent variants of the ATP7B gene were p.His1069Gln(c.3207A>G)in 38.24% of all alleles,p.Gly1341Asp(c.4021G>A)in 26.47%,p.Trp939Cys(c.2817G>T)in 9.80%,and p.Lys844Ter(c.2530A>T)in 4.90%.In ALF with hemolytic anemia,p.Trp939Cys(c.2817G>T)and p.Lys844Ter(c.2530A>T)variants were more frequent than in other less severe forms,in which p.His1069Gln(c.3207A>G)was more frequent.p.Gly1341Asp(c.4021G>A)has a similar frequency in all hepatic forms.For 33 of the patients,the HSD17B13 genotype was evaluated.The overall HSD17B13:TA allele frequency was 24.24%.Its frequency was higher in patients with less severe liver disease(26.92%)than those with ALF and hemolytic anemia(14.28%).CONCLUSION It remains challenging to prove a genotype-phenotype correlation in WD patients.In children with ALF and hemolytic anemia,the missense variants other than p.His1069Gln(c.3207A>G)and frame-shift variants were the most frequently present in homozygous status or compound heterozygous status with site splice variants.As genetic analysis is usually time-consuming and the results are late,the importance at the onset of the ALF is questionable.If variants proved to be associated with severe forms are found in the pre-symptomatic phase of the disease,this could be essential to predict a possible severe evolution.

Procedural learning changes in patients with Wilson's disease

In the present study, we compared explicit memory performance, using the Wechsler Memory Scale and implicit memory performance, using the Nissen software version of the serial reaction time task, in patients with Wilson＇s disease to normal controls. The Wilson＇s disease patients exhibited deficits in explicit memory tasks, such as figure recall and understanding memory. Moreover, the Wilson＇s disease patients exhibited deficits in implicit memory tasks, including significantly prolonged response times. These findings indicate that Wilson＇s disease patients have explicit and implicit partial memory impairments.

Practical insights into chronic management of hepatic Wilson’s disease

Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate

AIM:To investigate the side effects of a zinc sulphate therapy in a cohort of Polish pediatric patients with Wilson's disease. METHODS:We retrospectively analyzed a cohort of 53 pediatric patients with Wilson's disease treated at the Children's Memorial Health Institute in Warsaw, Poland between the years 1996 and 2011 with zinc sulphate. Patients were diagnosed with Wilson's disease according to the scoring system of Ferenci, with 49 cases confirmed by mutation analysis. Data about the dosage scheme of zinc sulphate, side effects and efficacy and toxicity of the treatment were collected and recorded in the patient's medical chart at each visit to the hospital. RESULTS:Mean age of diagnosis for the entire cohort was 10 years (range, 2.5-17 years). Duration of treatment with zinc sulfate was 83.3 wk (range, 8-344 wk). Side effects, all of gastrointestinal origin, were observed in 21 patients (40% 9 males and 12 females), irrespective of the duration of therapy. Thirteen out of 21 patients were over the age of 10 years. The most common ATP7B mutation was p.H1069Q. Esophagogastroduodenoscopy, performed in 7 patients (33.3%) suffering from persistent and severe abdominal pain, revealed gastrointestinal ulcerations or erosions with negative Helicobacter pylori tests in all subjects investigated. The above mentioned 7 patients were treated with proton pump inhibitors. Three of those experienced resolution of symptoms, whereas proton-pump inhibitors failed to alleviate symptoms of the remaining four children and conversion of therapy to D-penicillamine was needed. CONCLUSION:Zinc sulphate appears to cause significant gastrointestinal side effects, which children on therapy for Wilson's disease should be closely monitored for.

P wave dispersion is prolonged in patients with Wilson's disease

AIM:To investigate the P wave dispersion as a non-invasive marker of intra-atrial conduction disturbances in patients with Wilson's disease. METHODS:We compared Wilson's disease patients (n = 18) with age matched healthy subjects (n = 15) as controls. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary and hepatic copper concentrations). P wave dispersion, a measurement of the heterogeneity of atrial depolarization, was measured as the difference between the duration of the longest and the shortest P-waves in 12 lead electrocardiography. RESULTS:All the patients were asymptomatic on cardiological examination and have sinusal rhythm in electrocardiography. Left ventricular and left atrial diameters, left ventricular ejection fraction and left ventricular mass index were similar in both groups. The Wilson's disease patients had a significantly higher P wave dispersion compared with the controls (44.7 ± 5.8 vs 25.7 ± 2.5, P < 0.01). CONCLUSION:There was an increase in P wave dispersion in cardiologically asymptomatic Wilson's disease patients which probably represents an early stage of cardiac involvement.

Impact of COVID-19 pandemic on the neuropsychiatric status of Wilson’s disease

We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.

Assessment of LV Function in Children with Wilson’s Disease: Speckle Tracking Imaging Study

Background and Objective: Wilson’s disease is a genetic disorder of copper metabolism that affects liver and other organs including heart. In early stages of myocardial affection, the left ventricle (LV) appears apparently normal when evaluated by traditional two-dimensional (2D) echocardiography. The aim of this study was to detect subclinical LV dysfunction in children with Wilson’s disease using 2D speckle tracking echocardiography. Patients and Methods: Twenty children with Wilson’s disease were compared with age- and sex-matched 20 healthy children. All subjects were evaluated by traditional 2D echocardiography and speckle tracking echocardiography. Results: There were no significant differences between patients and controls regarding conventional echo parameters except for lower E mitral flow and E' annular septal peak velocity in patient group. The regional peak longitudinal strain of apical 4 chamber view was -17.8% ± 4.2% in patients and -20.1% ± 2.3 % in control subjects (P = 0.043), and for apical 2 chambers view, it was -20.1%± 3.6% in patients and -22.6% ± 3.4% in control subjects (P = 0.034) and it was -18% ± 3.5% in patients and -20.5% ± 3.2% in control subjects (P = 0.025) in apical long axis view. The global peak longitudinal strain was also lower in patients than control group (18.3% ± 3.2%, and 20.85% ± 2.4%) respectively (P = 0.014). There were no significant differences between both groups regarding circumferential and radial strains (P > 0.05). Conclusions: Despite apparently normal LV systolic function, the children with Wilson’s disease demonstrated significantly lower peak longitudinal strain as an indicator for early affection of LV systolic function.