Background: Wilson disease (WD) and tuberous sclerosis complex (TSC) are rare genetic disorders with distinct pathophysiologies. Their co-occurrence has not been previously reported. When atypical clinical features emerge in a patient with an established genetic diagnosis, comprehensive reassessment, including thorough physical examination and expanded genetic testing, becomes critical. Case Presentation: We describe a 28-year-old Chinese woman with a confirmed diagnosis of WD who developed focal seizures after substantial clinical improvement during copper chelation therapy. Her seizures were controlled with carbamazepine (600 mg/day), but repeated attempts to withdraw carbamazepine led to seizure recurrence, prompting diagnostic reassessment. Physical examination revealed characteristic TSC stigmata, including facial angiofibromas, periungual fibromas, a shagreen patch, and hypomelanotic macules. Laboratory evaluation demonstrated markedly low serum copper (1.38 & micro;mol/L) and ceruloplasmin (65.0 mg/L), along with elevated 24-h urinary copper excretion (218.20 & micro;g/24 h), measured during penicillamine treatment. Imaging showed nodular liver changes, a left renal hamartomatous lesion, bilateral basal ganglia abnormalities, a probable cortical tuber, and subependymal nodules. In January 2025, whole-exome sequencing identified a homozygous pathogenic ATP7B variant (NM_000053.4: c.2333G>T; p.Arg778Leu), confirming WD, and an apparently de novo heterozygous pathogenic TSC2 frameshift variant (NM_000548.5: c.2816dup; p.Ser939ArgfsTer21). The TSC2 variant was absent in both tested parents, but biological parentage was not independently confirmed. Conclusion: To our knowledge, this is the first reported case of concomitant WD and TSC. Given their distinct genetic etiologies, including a de novo TSC2 variant in this patient, the co-occurrence is most appropriately interpreted as an exceptionally rare independent dual diagnosis rather than evidence of a biological link. The case highlights diagnostic overshadowing and the importance of renewed physical examination and expanded genetic testing when the clinical course becomes atypical for an established disorder.
[1]Anhui Univ Chinese Med, Inst Neurol, Affiliated Hosp, Hefei, Anhui, Peoples R China.
[2]Wannan Med Univ, Wuhu, Anhui, Peoples R China.
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