R778L mutations in the ATP7B gene may be associated with an earlier presentation of Wilson disease (WD) and lower ceruloplasmin (CP) levels in Chinese patients, according to a systematic review and meta-analysis published in Pediatric Neurology.

Using a common-effect model, age was found to be significantly lower in patients with the R778L mutation than those without it (standardized mean difference [SMD], -.18; 95% CI, -.28 to -.08; P =.0004). These results included information from 1674 patients across 19 studies with no significant heterogeneity (I2 = 0%; P =.80).

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A significant association was also observed between patients with the R778L mutation and lower CP levels (SMD, -.21; 95% CI, -.40 to -.02; P =.03) in the 1553 patients included from the 13 eligible studies identified. Significant heterogeneity was observed in these studies, however (I2 = 51%; P =.02).

No significant correlations were observed between the R778L mutation and sex between the studies. No correlation was also observed between mutation status and the phenotypes of symptoms at first presentation, such as hepatic, neurologic, a mixture of the 2, or asymptomatic.

“Our meta-analysis supported that WD patients in China with R778L had a lower level of CP concentration and were younger at the time of onset, which might be valuable in the diagnosis or treatment of WD in clinical practice,” the authors wrote.

Subgroup analysis showed no difference between the northern and southern portions of China divided by the Qingling Mountain and the Huaihe River. 

Analysis based on reference type found that when the included data was limited to grey literature as defined by the Cochrane Handbook for Systematic Reviews of Interventions (including theses and ongoing reports) the significant correlations disappeared. When the study was limited to non-grey literature, which included published studies, the results were in conformity with the overall results.

Ultimately 23 studies were included in the review and meta-analysis, including the authors’ own laboratory experiments in 22 patients. Of the 22 patients directly analyzed by the authors, 11 patients had the R778L mutation, while the other 11 did not. Ultimately, the R778L mutation was present in 31.8% of alleles.


Xue Z, Chen H, Yu L, Jiang P. A systematic review and meta-analysis of the R778L mutation in ATP7B with Wilson’s disease in China. Pediatr Neurol. Published online May 8, 2023. doi:10.1016/j.pediatrneurol.2023.04.026