Introduction: The comorbidity of autoimmune hepatitis (AIH) and Wilson's disease (WD) can be considered, but has never been proven based on therapeutic response. There is a risk of misdiagnosis with standard diagnostic approaches. We describe a case of a challenging patients where final diagnosis could not be established with primary diagnostic approaches, and we question the coexistence of AIH and WD. Material and methods: We identified four cases among 165 patients with WD and 321 with AIH treated in our hospital, whose primary diagnosis was changed or questioned, analysis of which shows the difficulty in differentiating between these two diseases. Results: We presented four patients-three of them were diagnosed because of elevated serum aminotransferases activity and one due to acute hepatic failure. The three children were initially diagnosed as AIH, but after meticulous screening, WD was diagnosed. In the fourth case, WD was diagnosed from the beginning, but some autoimmune features and an incomplete response to the treatment prompted us to use steroids to achieve full recovery. Conclusions: WD can usually be distinguished from AIH, but in selected cases differential diagnosis is challenging. It seems to be extremely important to carry out a complete diagnostic set for WD in patients with initial diagnosis of AIH with poor response to steroids. In a large cohort of patients with WD and with AIH, only one seemed to have comorbidity, but even in this case AIH was not fully confirmed.

WD can present as early as 2 years of age. Because biochemical tests may be less sensitive in very young children, diagnoses may require a combination of tests. If molecular tests are inconclusive, liver copper content should be measured.

Background: Diagnosis of rare Wilson disease (WD) in pediatric patients is difficult, in particular when hepatic manifestation is absent. Genetic analysis of ATP7B represents the single major determinant of the diagnostic scoring system in WD children having mild symptoms.Objectives: To assess the impact of molecularly expressed ATP7B gene products in order to assist diagnosis of Wilson disease in pediatric patients having a novel mutation and subtle neuropsychiatric disease.Methods: The medical history, clinical presentation, biochemical parameters, and the genetic analysis of ATP7B were determined. Due to ambiguous clinical and biochemical findings and identification of a novel compound ATP7B mutation with unknown disease-causing status, a molecular analysis of the ATP7B gene products in a previously well characterized cell model was performed.Results: The ATP7B variants were transgenically expressed and the respective gene function molecularly characterized. Despite normal mRNA expression, low ATP7B protein expression of the mutants p.L168P and p.S1423N was observed (34.3 ± 8% and 66.0 ± 8%, respectively). Copper exposure did not result in decreased viability of transgenic cells as compared to wild type. Intracellular copper accumulation was reduced (≤47.9 ± 8%) and intracellular protein trafficking was impaired.Conclusion: Our report suggests that functional characterization of novel ATP7B mutants can assist diagnosis; however mild functional impairments of ATP7B variants may hamper the value of such approaches.

Wilson disease (WD) is a liver disorder characterized by improper copper metabolism. Although non-invasive tools are currently used to support diagnosis and management, this is still an area of unmet need, as patients present with a wide range of symptoms. Our aim was to investigate the potential utility of multiparametric magnetic resonance imaging (mpMRI) and quantitative magnetic resonance cholangiopancreatography (MRCP+) to support patient management. MRI examinations of 7 children and young adults aged 8–16 years (six at diagnosis) were performed alongside a standard of care clinical and histological examination. Images were quantitatively analyzed to derive metrics of liver (corrected T1 (cT1; fibro-inflammation), MR liver fat (proton density fat fraction; PDFF)), and biliary health (MRCP+). MRI–PDFF provided a more dynamic characterization of fat compared with that provided by ultrasound. Those with elevated histological scores of fibrosis, inflammation, and steatosis had elevated mpMRI values. MRCP+ managed to identify dilatations in the biliary tree which were not observed during the standard of care examination. mpMRI and MRCP+ metrics show early promise as markers to assess both liver and biliary health in Wilson disease. Investigations to understand and explore the utility of these markers are warranted and should be performed.

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