Low serum creatinine levels and an age of less than 35 years appear to be independent risk factors associated with Wilson disease (WD) and could help distinguish patients with WD and normal ceruloplasmin levels from patients with liver disease due to other causes, according to a recently published study in the International Journal of Clinical Practice.

Low ceruloplasmin levels (<200 mg/L) are considered a diagnostic hallmark of WD, with the majority of patients having less than half of the cut-off values. However, many patients with WD have normal ceruloplasmin levels; in particular, patients with acute liver failure due to WD tend to have low-normal levels of ceruloplasmin.

Read more about WD diagnosis

This subset of patients is easily identifiable by measuring the aspartate aminotransferase:alanine aminotransferase ratio. On the other hand, patients with WD who are not in acute liver failure and have normal ceruloplasmin levels represent a diagnostic challenge.

Therefore, the authors performed a retrospective cohort study to identify factors that could help distinguish patients with WD and normal ceruloplasmin levels from those with other liver pathologies and to determine factors related to ceruloplasmin normalization in WD. The study included 86 patients with WD and serum ceruloplasmin levels over 140 mg/L. All relevant clinical information, such as laboratory results, mutational sites of the ATP7B gene, and radiological findings, were thoroughly analyzed in the search for indicators associated with higher ceruloplasmin levels.

The findings were compared to those of a control cohort comprising patients with liver diseases other than WD, for example, nonalcoholic steatosis hepatitis and viral hepatitis.

Patients in the WD group were subdivided into 2 groups depending on their serum ceruloplasmin levels, revealing that increased ceruloplasmin levels were associated with increased liver damage, liver cirrhosis, and increased urinary copper excretion. The study did not provide any evidence that the ATP7B gene mutation type had any correlation with ceruloplasmin levels.

The logistic regression model revealed that patients with WD-associated liver disease had lower creatinine levels and were more likely to be under the age of 35 years than patients from the control cohort. The authors explain these findings, pointing out that other causes of liver damage such as hepatitis take decades to lead to liver failure.

Therefore, patients with WD-associated liver disease tend to be younger. Researchers hypothesize that WD leads to increased oxidative stress that, in turn, results in creatine depletion.

“A regression model was established with usual indicators, age and serum [creatinine], which have good performance in identifying suspicious WD patients from undefined patients whose serum [ceruloplasmin] ≥140 mg/L,” the authors concluded.


Chen L, Shi Y, Wang N, et al. Age and serum creatinine can differentiate Wilson disease patients with pseudonormal ceruloplasmin. Int J Clin Pract. 2023;2023:9344891. doi:10.1155/2023/9344891