There is significant heterogeneity in the diagnosis and management of Wilson disease across reference centers in Spain, whether large or small, according to a new multicenter cohort study published in Gastroenterología y Hepatología.

The authors of the study suggest that the incorporation of genetic testing could improve the diagnosis of the disease.

To explore whether the approach to Wilson disease was homogeneous among different centers, a team of researchers led by Rocio Gonzalez, MD, from Servicio de Aparato Digestivo, Hospital Regional Universitario de Málaga in Spain collected data on patients with Wilson disease who were followed at 31 hospitals in Spain. 

They identified 153 patients with the disease, of whom 58% were male and 69.1% had a hepatic presentation. The average age of the patients at diagnosis was 20.6 years, and they were followed for an average of 15.5 years.

Read more about the diagnosis of Wilson disease

The results showed that for 39.8% of noninvasive laboratory parameters, there were discordant results between centers. In 82.4% of cases, the concentration of intrahepatic copper was pathologic. 

In only 56.6% of cases, a genetic test was done, and 83.9% of tested cases yielded positive results. 

A definitive diagnosis of Wilson disease was confirmed in 92.5% of cases retrospectively. 

In 75.2% of cases, the standard initial therapy consisted of chelating agents. Treatment was often modified to maintenance zinc. 

In one-third of cases, enzyme normalization was not achieved, mostly due to poor compliance to treatment, a lack of genetic mutations, or cardiometabolic risk factors. 

The researchers also found trends for sex differences in the number of diagnosed cases, the age of the patient at diagnosis, and their biochemical response to treatment. However, statistical significance was not reached.

“Sex differences need to be further explored,” the researchers concluded.


Berenguer M, Vergara M, Almohalla CC, et al. Significant heterogeneity in the diagnosis and long-term management of Wilson disease: results from a large multicenter Spanish study. Gastroenterol Hepatol. Published online November 11, 2022. doi:10.1016/j.gastrohep.2022.10.018