Case Report: Co-occurrence of Wilson disease and tuberous sclerosis complex in a Chinese patient

Abstract

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 μmol/L) and ceruloplasmin (65.0 mg/L), along with elevated 24-h urinary copper excretion (218.20 μg/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.