Wilson’s disease (WD), a rare cause of neuropsychiatric deterioration, is associated with mutations in the
ATP7Bgene. Prion diseases are also rare causes of neuropsychiatric deterioration that can occur sporadically without an identifiable cause, or can be attributed to mutations in the PRNPgene. Case presentation
Here we describe a biological “experiment of nature” in which a patient presented with severe neuropsychiatric decline and strong biochemical evidence of WD. Genetic analysis revealed that he was a compound heterozygote for two
ATP7Bsequence variants (c.2165dupT, p.Arg723Glufs*32; and c.4039G > A, p.Gly1347Ser), the first having been reported once previously, and the second being novel. In addition, the patient was heterozygous for a PRNPvariant, c.160G > A, p.Gly54Ser, that has been reported in a neuropsychiatric patient only once previously in association with a similarly severe clinical course of neuropsychiatric disease and early age of onset, but no accompanying information on ATP7Bgenotype. Of particular interest was the observation that the patient’s older sister, who carried the same ATP7Bgenotype and laboratory evidence for biochemical WD but was clinically asymptomatic, lacked the PRNPvariant allele. Conclusions
We propose that synergism may occur between at least some allelic variants of
ATP7Band PRNP, possibly exerted through effects on cellular copper metabolism.