Like many other rare diseases that do not necessarily present with clear, pathognomonic features, Wilson disease can develop under the radar and go unnoticeable for years. This means that physicians rarely pursue the necessary investigations to arrive at a correct diagnosis. 

Additionally, Wilson disease may only become obvious at seemingly random points of the disease, meaning it has a highly heterogeneous presentation. Patients may present at a young age, when the disease is still relatively mild, or later in life, when the disease is more advanced. 

“Conversely, Wilson’s disease can also be misdiagnosed as a result of misinterpreting the medical findings,” Hermann wrote in the Annals of Translational Medicine.

Differing Types and Presentations

In Wilson disease, copper overload exerts toxicity via 2 main mechanisms: the buildup of free copper in the bloodstream, which is harmful to the host, as well as the alteration of copper-carrying ATP genes in the liver, which causes liver impairment within the first decade of life.

The disease can be broadly categorized into 2 forms: non-neurological forms of progression and neurological forms of progression. In non-neurological forms of this disease, preclinical symptoms are typically absent, but liver pathology can be significant (such as acute/chronic decompensated liver disease and liver cirrhosis). 

Read more about Wilson disease etiology 

In neurological forms of the disease, a plethora of symptoms may be noticeable. For example, pseudoparkinsonism may present as bradykinesia/hypokinesia, postural-intentional tremor, and dysarthria. Meanwhile, pseudosclerotic symptoms may include flapping and intention tremor, cerebellar ataxia, and dysarthria. 

In addition, Wilson disease tends to have a slightly different presentation according to age. Before a patient reaches pubertal age, gastrointestinal symptoms with hepatic/hemolytic findings tend to be more prominent. After puberty, symptoms affecting the central nervous system may take center stage; these include extrapyramidal and mental manifestations. 

Extensive Investigations May Be Needed

In the Journal of Current Medical Research and Opinion, Dutta et al presented the case of a 17-year-old male patient diagnosed with Wilson disease. The patient’s medical history included irregular behavior and movement of hands, followed by a dwindling ability to talk. Since the patient had been bedridden for a period of time, forcible bed sores were noted. The patient did not have a history of seizures. 

The patient underwent an Inductively Coupled Plasma Mass spectrometry (ICPMS), which is a technology that can detect levels of heavy traced copper materials in biological tissues. Other tests were also conducted to determine the patient’s copper levels: a urine assay results were 1200 ml/day and was associated with Wilson disease, and a test ceruloplasmin serum revealed 25.83 mg/dl of copper in the body. In addition, a total leucocyte count was abnormally high (15.4H; normal range: 4.0-10.0). 

The patient’s physicians started him on third-generation antibiotics followed by parkinsonism treatment; he was also prescribed general medications to regulate his heart rate and maintain gastrointestinal health. His apparent Wilson disease was then managed by efficient intake of zinc and magnesium supplements in food.

Utilizing Differential Diagnosis 

According to Dutta and colleagues, the most frequent incorrect diagnosis in a presentation of mild liver illness is viral hepatitis. The conclusive way to rule out Wilson disease is to conduct copper studies. In fact, copper studies should be pursued with the exhibition of tremors similar to early Parkinson’s disease and signs of psychiatric illness. 

In Wilson disease, an overabundance of copper accumulates in several human tissues. This may include the brain, liver, and corneas of the eyes. The natural progression of Wilson disease is that central nervous system dysfunction and hepatic disease develops, and if left untreated, may result in mortality. 

“Preventing major long-term impairment and potentially fatal complications may be possible with early diagnosis and treatment,” Dutta et al wrote. 

Read more about Wilson disease treatment

The chief goal of Wilson disease therapy is to bring excessive copper levels in the body down to normal levels. That treatment is largely effective; the main problem hampering efforts to treat individuals with Wilson disease is misdiagnosis. In other words, it is not the therapeutics that are lacking, but the insidious ways in which Wilson disease often develops in the human body while undetected for large periods of time. 

Nevertheless, a healthy clinical suspicion based on the symptoms described in this article, combined with an expansive laboratory investigation, should be sufficient to point physicians in the right direction. Once a diagnosis of Wilson disease is confirmed, physicians can focus all their efforts on normalizing copper levels and preventing further organ deterioration. 

“On the one hand, starting treatment for Wilson’s disease early on is required but on the other hand, only a reliable diagnosis justifies treatment, which involves adverse reactions,” Hermann wrote. “Starting treatment at an early stage, avoiding wrong medication and the prognostic assessment are also significant for differential diagnoses.”


Dutta S, Sarma SN, Gupta S, et al. Essential case report study on Wilson disease. Curr Med Res Opin. Published online September 5, 2022. doi:10.52845/CMRO/2022/5-9-2

Hermann W. Classification and differential diagnosis of Wilson’s diseaseAnn Transl Med. 2019;7(Suppl 2):S63. doi:10.21037/atm.2019.02.07