Tomasz Litwin

Institute of Psychiatry and Neurology · Second Department of Neurology

Introduction: Wilson’s disease (WD) is a potentially treatable, inherited disorder resulting from impaired copper metabolism. Pathological copper accumulation causes a range of symptoms, most commonly hepatic and a wide spectrum of neurological symptoms including tremor, dystonia, chorea, parkinsonism, dysphagia, dysarthria, gait and posture distur...

Objective: D-penicillamine (DPA) belongs to the most frequently used drugs in Wilson’s disease (WD) treatment. Despite the effectiveness in WD treatment, DPA could be involved in many adverse drug reactions (ADRs), which should be recognized early. Background: WD is a genetic disorder with copper accumulation in tissues leading to clinical symptoms...

Objective: Minimum clinically important differences (MCID) on the Unified Wilson Disease Rating Scale (UWDRS) Part III were estimated using data from a phase III trial of tiomolibdate choline (TMC; INN: tiomolibdic acid; ALXN1840) vs standard of care (SoC) in patients (pts) with Wilson disease (WD). Background: FoCus is an open-label randomized tri...

La EW es causada por las variantes de ATP7B que alteran el eflujo de cobre y provocan una acumulación excesiva de cobre, principalmente en el hígado y el cerebro. El diagnóstico de la EW se ve dificultado por su evolución clínica variable, su aparición, su morbilidad y el tipo de variante ATP7B. Actualmente se diagnostica mediante una combinación d...

Wilson’s disease (WD) is a genetic disorder with copper accumulation in various tissues leading to related clinical symptoms (mainly hepatic and neuropsychiatric) which can be in 85% of patients successfully treated with anti-copper agents. However, during WD treatment neurological deterioration may occur in several patients. D-penicillamine (DPA)...

Introduction. Our study assessed changes in concentrations of serum markers for brain damage and blood-brain barrier (BBB) dysfunction in untreated and treated Wilson’s disease (WD) patients, and examined correlations between these changes and neurological impairment. Objective. These results hold the potential to determine BBB impairment and neur...

Background: Treatment of Wilson’s disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may occur. We systematically reviewed the literature to describe treatment patterns, symptoms and outcomes associated with CD. Methods: Using preferred reporting items for syste...

Background and aims: Wilson’s disease (WD) is a genetic disorder with copper accumulation in tissues leading to clinical symptoms (mainly hepatic, neuropsychiatric). The copper metabolism results in WD patients show increased serum “free copper” with its normalization during WD treatment. As WD treatment is lifelong, the possibility of copper...

Background and aims: In Wilson’s disease (WD), free copper may impair the blood-brain barrier (BBB) function and contribute to central nervous system damage. The study assessed changes in serum concentrations of BBB integrity markers in untreated and treated WD patients and examined correlations between these changes and neurological impairme...

Introduction Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson’s disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors. Methods Using...

Purpose: Access to electroneurographic/electromyographic (ENG/EMG) examinations and the number of patients referred for electrodiagnostic (EDX) examination are increasing. We aimed to determine the accuracy of the initial clinical diagnosis made by outpatient medical care physicians who referred patients to the EMG laboratory. Methods: We analyz...

Wilson's disease (WD) is an inherited disorder of copper metabolism with clinical symptoms related to pathological copper accumulation, which are mainly hepatic and/or neuropsychiatric. The disease is potentially treatable with pharmacological agents (chelators or zinc salts). As such, key factors for a favorable treatment outcome are early diagnos...

Introduction. Many neurodegenerative disorders are associated with olfactory dysfunction (OD), but little is known about OD in Wilson’s Disease (WD). We evaluated olfactory function in patients with WD. Material and methods. OD was examined in 68 patients with WD and 70 sex- and age-matched healthy controls using subje�ctive testing with‘Sniffin S...

Objectives. Wilson’s disease (WD) is a genetically inherited disease associated with disorder of copper metabolism and its pathological deposition in many organs (mainly in the liver and brain) and their secondary damage. Clinical symptoms of WD are mainly symptoms of liver damage (from a mild increase in the activity of liver enzymes to liver...

Introduction: Wilson's disease (WD) is a treatable genetic disorder caused by impaired copper metabolism. Early diagnosis and correct anti-copper treatment are crucial for therapeutic success. Brain magnetic resonance imaging (MRI) is used both for diagnosis and treatment monitoring. Several neuroradiological signs have been proposed to be pathogno...

Background: Wilson's disease (WD) is a rare autosomal recessive disorder causing excessive copper deposition and a spectrum of manifestations, particularly neurological and hepatic symptoms. Over seven decades (<1959 to 2019), we analysed the clinical characteristics of patients with WD admitted to the country's only reference centre, which provid...

Background Although brain atrophy is common in neurological Wilson's disease, longitudinal studies are lacking. Objective The objective of this study was to measure longitudinal brain atrophy rate and to relate it to the change in neurological impairment in Wilson's disease. Methods We included patients with brain imaging done at diagnosis and at...

Objectives/introduction: Wilson's disease is a disorder of copper metabolism which causes its accumulation in various organs – mainly in liver or brain. It is a liver as well as a neurodegenerative disorder and may lead to sleep disturbance (SD). It maybe be expected that SD will show similar prevalence among individuals with Wilson's disease as wi...

Background In Wilson’s disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD. Methods Early neurological deterioration, within 6 months from diagnosis, was d...

Purpose Wilson's disease (WD) is an inherited disorder involving copper accumulation in the liver and brain. An important mechanism responsible for hepatocyte injury in WD is mitochondria destruction, although damage may also be caused by oxidative stress and lipid peroxidation. Patients/methods The study included 54 treated patients with WD witho...

Background: Wilson's disease (WD) is a rare, autosomal disorder of copper metabolism, in which antibodies mediate and modulate the clinical manifestation of the CNS disease. The aim of this study was to investigate the presence and impact of autoantibodies in the clinical course of WD. Method: Study involved 88 WD diagnosed and already treated pati...

Wilson's disease (WD) is a rare, treatable genetic disorder with multi-organ symptoms related mainly to copper accumulation. Most patients become aware of the disease as young adults, thus knowledge on fertility, pregnancy course and outcome is very important both for patients and physicians. The aim of this study was to perform a systematic review...

Symptoms of Wilson disease (WD) vary and additional factors such as autoimmu-nity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies, neuronal surface anti-bodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays an...

Background and aims: Early neurological deterioration in Wilson’s disease (WD) is one of the main challenges in disease management. It may happen even on anti-copper therapy, especially with d-penicillamine, however a lot of questions are open. Aim of our approach was to determine the frequency and risk factors of early neurological deterioration i...

Background and aims: WD is a rare genetic disorder causing copper accumulation and subsequent liver and brain damage. Since the end of the 1950s, life-long anti-copper therapies (mainly d-penicillamine - DP, trientine, zinc salts) have been available. We present seven decades of experience of a single reference centre covering most adult Wilson dis...

I won the 1st prize at the Internal Medicine Session held during the 30th International Medical Students Conference Cracow in the beginning of June 2022. My work was titled: “Long Term Follow-Up of Wilson Disease Patients in Poland - Report from the National Reference Center”, mentored by Dr hab. n. med. Maciej Niewada and Prof. dr hab. n. med. An...

Background: In mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA) associated with C19orf12 mutations, patients suffer from: dystonia, parkinsonism, optic nerve atrophy and dementia. Previous studies showed the de- crease in heart rate variability (HRV) in 24-h Holte...

The metabolic disorder Wilson’s disease (WD) is caused by copper accumulation in the tissues due to a biallelic pathogenic mutation of the gene ATP7B, encoding intracellular copper transporter ATPase-7B. As copper is a redox active metal; aberrations in its homeostasis may create favourable conditions for superoxide-yielding redox cycling and oxida...

Background and aim: Since the first desription of hepatolenticular degeneration by SK Wilson the expertise about Wilson disease (WD) clinic, pathogenesis, diagnosis and therapy has increased our daily practice. The aim of our study is to present seven decades of experience of a single reference centre covering most adult WD patients in Poland Metho...

Background and aim: Copper deposition may lead to inflammation in organs and tissues of Wilson's disease (WD) patients, impairing the blood-brain barrier (BBB) function and accelerating brain injury. Therefore, our study aimed to follow-up changes in markers for the BBB integrity in untreated and treated WD patients. Methods: One hundred seventy-on...

Background: Aceruloplasminemia is an ultra-rare, adult onset, autosomal recessive disease, one of the neurodegeneration with brain iron accumulation (NBIA). It is caused by mutations in the ceruloplasmin gene (CP), encoding ceruloplasmin. Ceruloplasmin is a multicopper oxidase with ferroxidase activity that oxidizes ferrous iron which enables its t...

Background: early neurological deterioration in Wilson’s disease (WD) after treatment initiation is still one of the main challenges of WD treatment and often predicts its outcome. The available evidence on this phenomenon is conflicting, with a lack of reliable biomarkers. The aim of our study was to investigate risk factors of early neurological...

Introduction Most neurodegenerative and chronic liver disorders are associated with sleep disturbances (SD). SD may be expected to occur in patients with Wilson’s disease (WD), an inherited disorder of copper metabolism that mostly afects the liver and brain; however, there is a lack of observations, particularly in treatment-naïve WD patients. M...

Introduction Wilson’s disease (WD) is a genetic disorder with pathological copper accumulation and associated clinical symptoms in various organs, particularly the liver and brain. Neurological disease is assessed with the clinical Unifed Wilson’s Disease Rating Scale (UWDRS). There is a lack of quantitative objective markers evaluating brain invol...

Background Clinical scales and neuroimaging are used to monitor nervous system injury in Wilson's disease, while data on serum markers are scarce. Objective To investigate whether serum concentrations of neurofilament light chain (sNfL) correlate with brain injury in Wilson's disease patients. Methods In 61 treatment-naïve patients, the Unified Wil...

Introduction Wilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. However, in almost 50% of WD patients, neurological symptoms persist despite treat�ment, and in up to 10% of patients, neurological deterioration is irreversible. International guidelines...

Aceruloplazminemia należy do rzadkich, genetycznie uwarunkowanych zaburzeń metabolizmu żelaza. Schorzenie to dziedziczy się w sposób autosomalny recesywny i jest spowodowane przez mutacje w genie kodującym białko ceruloplazminę zlokalizowanym na chromosomie 3. Ceruloplazmina dzięki aktywności ferrooksydazy bierze udział w utlenianiu jonów żelaza. B...

Choroba Wilsona u osób dorosłych przebiega najczęściej z objawami wątrobowymi (od bezobjawowego wzrostu enzymów wątrobowych, objawy przypominające ostre zapalenie wątroby czy skompensowaną lub zdekompensowaną marskość wątroby) i/lub neurologicznymi (szerokie spektrum ruchów mimowolnych). Według różnych danych większość pacjentów w przebiegu choroby...

Abnormal blink refex (BR) results mainly from the dysfunction of reticular brainstem pathways and is one of the features of degenerative brain disorders. We aimed to investigate whether patients with Wilson’s disease (WD) have abnormal BR. This was a prospective, observational, single-center study. BR was assessed in accordance with generally acce...

Objectives. Wilson’s disease (WD) is a genetic, neurodegenerative disorder caused by copper metabolism disturbances with subsequent pathological copper accumulation in organs and tissues (mainly liver and brain) with their secondary damage and clinical symptoms related to affected organs. The treatment of the disease is based on medications leadin...

Wilson’s disease (WD) is an autosomal recessive genetic disorder of copper metabolism leading to liver or brain injury due to accumulation of copper. Diagnosis is based on: clinical features, biochemical tests including plasma ceruloplasmin concentration, 24h urinary copper excretion, copper content in the liver, and molecular analysis. Pharmacolog...

Purpose: To investigate whether patients with Wilson disease have abnormal motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation. Methods: In a prospective, observational, single-center study, transcranial magnetic stimulation was used to examine MEPs recorded from the abductor digiti minimi in 24 newly diagnosed treatment-na...

Objective: Wilson’s disease (WD) is an inherited disorder of copper metabolism with copper accumulation in different organs and clinical symptoms related to the affected organs (mainly hepatic and/or neuropsy-chiatric). D-penicillamine (DPA) is a drug frequently used in WD therapy.Background: DPA may cause adverse drug reactions (ADRs) whichjustify...

Objective: We present seven decades of experience of a single refer-ence centre covering most adult Wilson disease (WD) patients in Poland.Background: WD is a rare genetic disorder causing copper accumula-tion and subsequent liver and brain damage. Consequently, two symptom-atic forms, neurological and hepatic, are recognized; additionally,presympt...

WD is caused by ATP7B variants disrupting copper efflux resulting in excessive copper accumulation mainly in liver and brain. The diagnosis of WD is challenged by its variable clinical course, onset, morbidity, and ATP7B variant type. Currently it is diagnosed by a combination of clinical symptoms/signs, aberrant copper metabolism parameters (e.g.,...

Wilson's disease (WD) is a rare hereditary disorder of copper metabolism. Some data suggest that iron metabolism is disturbed in WD and this may affect the course of the disease. The current study aimed to determine whether anti-copper treatment could affect iron metabolism in WD. One hundred thirty-eight WD patients and 102 controls were examined....

Wilson's disease (WD) is a rare hereditary disorder of copper metabolism. Some data suggest that iron metabolism is disturbed in WD and this may affect the course of the disease. The current study aimed to determine whether anti-copper treatment could affect iron metabolism in WD. One hundred thirty-eight WD patients and 102 controls were examined....

Choroba Wilsona (WD, Wilson’s disease) jest schorzeniem genetycznym, dziedziczonym autosomalnie recesywnie, związanym z zaburzeniami metabolizmu miedzi, które prowadzą do odkładania się jej w wielu narządach i tkankach. Główne objawy kliniczne wynikają z uszkodzenia wątroby i mózgu. Choroba ta zwykle jest skutecznie leczona, a nawet można zapobiec...

Choroba Wilsona (WD, Wilson’s disease) jest schorzeniem genetycznym związanym z patologicznym odkładaniem miedzi w wielu narządach (głównie wątroba, mózg i rogówka), z objawami klinicznymi w zależności od uszkodzonych tkanek i narządów. Głównym celem leczenia WD jest przywrócenie prawidłowego lub wytworzenie negatywnego bilansu miedzi w organizmie...

Objective: Wilson's disease (WD) is a genetic disorder with pathological copper accumulation in different organs with clinical symptoms related to damage of affected tissues (mainly hepatic or/and neurological). The advance of neurological disease in WD was usually assessed with physical examination. Currently the clinical scales like Unified Wilso...

Introduction: Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare genetic disorders associated with progressive movement disorders and excessive iron accumulation in the brain. One of the NBIA subtypes, mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by a mutation in the orphan gene C19orf12,...

Objective: Wilson's disease is genetically induced failure of cooper metabolism that can be successfully treated with pharmacological agents. However, approximately 25% of patients do not take medication regularly, which impacts treatment effectiveness. We present a case report of a patient who after initial improvement, deteriorated due to treatme...

Objective: Diagnosis of Wilson's disease (WD) is based on the presence of clinical symptoms, laboratory (serum ceruloplasmin, serum copper, urinary copper excretion) and genetic findings. Diagnostic criteria of WD are summarized in Leipzig scoring. Radioactive copper incorporation is used when standard diagnostic criteria are insufficient. Methods...

Objective: Wilson's disease (WD) is a hereditary disorder of copper metabolism. The metabolic pathways of copper and iron are interrelated. Our goal was to determine the frequency of the two most common mutations in the coding region of the human iron homeostatic protein gene (HFE) in Europe: C282Y (rs1800562) and H63D (rs1799945) in WD patients, a...

Background and Aims: Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, with its main pathology attributed to copper-mediated oxidative damage. The limited therapeutic effect of copper chelators and the early occurrence of mitochondrial deficits, however, undermine the prevalence of this mechanism. Methods: We characterized...

Introduction: In mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA), patients suffer from optic nerve atrophy and dementia, which are also typical for another group of diseases, the mitochondrial diseases (MD). Around 30% of patients with MD have heart disease, com...

Background/aim Wilson’s disease (WD) is a hereditary disorder characterized by abnormal metabolism of copper. For unknown reasons, the clinical picture of this disease appears to be sex-dependent. Because the metabolism of copper and iron is interrelated, we aimed to evaluate whether the variability in the clinical picture of WD could be explained...

Objectives: Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson's disease. To evaluate the accuracy of collagen proportionate ar...

Objectives: Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson's disease. To evaluate the accuracy of collagen proportionate a...

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...

Introduction: Wilson's Disease (WD) is an inherited disorder of impaired hepatic copper metabolism that leads to copper accumulation in organs such as the liver and brain. Using transcranial sonography (TCS), we investigated brain changes in WD patients during de-coppering treatment. Methods: Forty-one consecutive treatment-naïve WD patients wer...

Background MRI is a sensitive method for the assessment of brain abnormalities in Wilson disease, that is, T2 hyperintensities, T2 hypointensities, and atrophy, but a validated scoring system for the classification of radiological severity is lacking. The objective of this study was to develop and validate a brain MRI visual rating scale for Wilson...

Background. In multiple sclerosis (MS), insufficient blood supply might worsen energy deficiency of the brain tissue. Thus, cerebrovascular reactivity (CVR), which is the capacity of cerebral circulation to match blood supply to metabolic demand, might be important in MS pathology. Objectives. The objective of this study was to investigate the rela...

Background: Gastrointestinal symptoms are common in patients with Wilson disease (WD) and may be related to the disease itself or to adverse drug reactions (ADRs). Aim: To investigate gastroscopy findings in patients with WD and to analyze the risk of gastropathy in the context of different manifestations and treatments of WD as well as Helicobacte...

In the originally published version of this article, there was an error. The metabolomics platform used for the analysis is GCTOF-MS, Gas Chromatography Time-of-Flight Mass Spectrometry and not Hydrophilic Interaction Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry as indicated in the original version. The wrong methodology is rep...

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylch...

Background: Wilson disease (WD) is genetically induced failure of copper metabolism which can be successfully treated with pharmacological agents. The prognosis for survival in most WD patients is favorable if diagnosis and anti-copper treatment are provided early. Many observations imply that persistence with drug treatment is generally low in pa...

Wilson disease (WD) is a genetic copper overload condition, with variable clinical presentation, including hepatic and neuropsychiatric manifestations. The pathogenesis of WD is not understood. A major role is played by reactive oxygen species (ROS) production with consequent damage affecting cellular organelles and bioenergetics. Choline is an ess...

Abstract Background Wilson disease (WD) is a genetic disorder involving impaired copper metabolism, which presents with hepatic, neurological, and/or psychiatric manifestations. WD requires lifelong pharmacotherapy and treatment persistence may be problematic. We studied social characteristics, education, and work-related activities and how they ar...

Introduction: Wilson’s disease (WD) is one of the few genetic disorders that can be successfully treated if diagnosed early and treated correctly. Currently two group of drugs are used in WD treatment: chelators or zinc salts. Both treatments lead to negative copper body balance, reversing the pathological accumulation of copper in tissues and remo...

Neurological impairment is a characteristic of Wilson disease (WD) and is the first clinical symptom in nearly 50% of patients. Copper accumulates in all parts of brain tissues in WD, but the greatest injury is observed in basal ganglia. Characteristics include pathological forms of astroglia, neuronal death, and brain atrophy. The neurological man...

Introduction To determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson’s disease. Methods In 48 treatment-naïve patients, we assessed functional and neurological impairments with the Unified Wilson’s Disease Rating Scale, measured normalized brain volumes...

Neurologic symptoms in Wilson disease (WD) appear at an older age compared to hepatic symptoms and manifest in patients with misdiagnosed liver disease, in patients when the hepatic stage is clinically silent, in the case of non-compliance with anti-copper treatment, or with treatment failure. Neurologic symptoms in WD are caused by nervous tissue...

Background and aims:Wilson disease (WD) is a genetic disease due to copper accumulation in the liver and brain. The clinical presentation is variable and suggests that environmental factors through epigenetic mechanisms may contribute to the disease phenotype. Histone deacetylases (HDACs) remove acetyl moieties from lysine residues of histone tails...