Wilson disease is a rare, autosomal recessive, inherited disorder of copper metabolism characterized by the excessive accumulation of copper throughout the organs and tissues, especially the liver, brain, and eyes.1

Wilson disease affects around 1 in every 30,000 people and manifests at varying ages, ranging from 1 to 70 years. Disease onset most commonly occurs between the ages of 5 and 45 years.1,2

Initial symptoms in children and young adults commonly involve the liver, the primary site of copper metabolism; however, the first symptoms to manifest in individuals diagnosed at later ages are often neurological or psychiatric in nature.1 

Common Comorbidities

Researchers examined common and severe comorbidities in 3242 adults with Wilson disease. Almost all of the patients (96.3%) demonstrated at least 1 hepatic, psychiatric, neurologic, renal, cardiac, or pain-related comorbidity.3

Hepatic 

Hepatic comorbidities occurred in 44% of patients. The most common hepatic comorbidities included ascites/edema (21.4%), liver cirrhosis (20.4%), fatty liver (19.6%), portal hypertension/varices (11.8%), and acute hepatic failure (11.4%). Of the 3242 patients, 9% underwent liver transplantation.3

Psychiatric 

Psychiatric comorbidities included anxiety (34%), depression (31.9%), insomnia (14.3%), mood disorders (11.3%), encephalopathy (9.6%), and schizophrenia (6.3%).3 Another study reinforced the need to rule out psychiatric comorbidities in patients with Wilson disease due to these comorbidities causing decreased quality of life and worse psychosocial outcomes.4

Other 

Other comorbidities experienced by the 3242 adults with Wilson disease included pain-related (70.5%), renal (66.6%), neurologic (55%), and cardiac (28.8%) problems.3

Rare Comorbidities in Case Studies

Several researchers have published case studies describing comorbid conditions in patients with Wilson disease. One case study described a 37-year-old woman with a complicated medical history including fibromyalgia, microscopic colitis with chronic secretory diarrhea, severe chronic obstructive pulmonary disease, electrolyte abnormalities, hepatic enzyme elevation, hyperammonemia, borderline personality disorder, bipolar disorder, and persistent methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. She was hospitalized for sepsis secondary to bowel perforation. While in the hospital, she was found to have low serum ceruloplasmin levels and acute liver failure with encephalopathy following a workup for liver disease, resulting in her eventual diagnosis of Wilson disease.5

Another case study presented a rare combination of 3 genetic diseases in a 15-year-old boy who had comorbid fulminant-type Wilson disease, Gitelman syndrome, and hereditary sensory autonomic neuropathy type IV.6 

A third case study described a 44-year-old man diagnosed with Wilson disease (hepatolenticular degeneration) who presented with mild hepatic damage, psychiatric symptoms, difficulty speaking, and cognitive impairments. He exhibited motor aphasia and psychomotor delays. Following lumbar puncture, prion proteins (PrPSc) were detected in the patient’s cerebrospinal fluid. Brain magnetic resonance imaging confirmed elevated signals in the basal ganglia and a cortical ribbon sign in the cerebral cortex, indicating not only Wilson disease but also Creutzfeldt-Jakob disease. This case study suggests that Creutzfeldt-Jakob disease and Wilson disease might share a common pathogenic origin related to copper.7

Renal/Musculoskeletal 

Renal and musculoskeletal comorbidities include kidney stones and metabolic bone disease, which may manifest as rickets, osteoporosis, osteopenia, osteomalacia, lower limb deformities, and renal tubular acidosis.8-10

Hematologic 

Coombs-negative hemolytic anemia co-occurs in around 10% to 15% of patients with Wilson disease. Researchers speculate that the early destruction of erythrocytes occurs due to oxidative stress, membrane damage, and the inactivation of glycolytic pathways and pentose phosphate enzymes caused by the storage of excess copper within red blood cells.11

References

  1. Wilson disease. MedlinePlus. Updated July 11, 2022. Accessed September 16, 2022.
  2. Hermann W. Classification and differential diagnosis of Wilson’s disease. Ann Transl Med. 2019;7(Suppl 2):S63. doi:10.21037/atm.2019.02.07
  3. Kruger E, Nedzesky J, Thomas NA, Cataldo J. Common and serious comorbidities among adults with Wilson disease. Value Health. 2021;24(Suppl 1):S211. doi:10.1016/j.jval.2021.04.1057
  4. Mura G, Zimbrean PC, Demelia L, Carta MG. Psychiatric comorbidity in Wilson’s disease. Int Rev Psychiatry. 2017;29(5):445-462. doi:10.1080/09540261.2017.1311845
  5. Culpepper T, Kelkar AH. Undiagnosed Wilson’s disease and fibromyalgia masking bowel perforation. Cureus. 2021;13(2):e13504. doi:10.7759/cureus.13504
  6. Kim JY, Park SS, Yang HR. Wilson disease comorbid with hereditary sensory autonomic neuropathy type IV and Gitelman syndrome. Pediatr Gastroenterol Hepatol Nutr. 2019;22(4):392-399. doi:10.5223/pghn.2019.22.4.392
  7. Koutsouraki E, Michmizos D, Patsi O, et al. A probable role of copper in the comorbidity in Wilson’s and Creutzfeldt-Jakob’s diseases: a case report. Virol J. 2020;17(1):35. doi:10.1186/s12985-020-01309-x
  8. Wiebers DO, Wilson DM, McLeod RA, Goldstein NP. Renal stones in Wilson’s disease. Am J Med. 1979;67(2):249-254. doi:10.1016/0002-9343(79)90399-1
  9. Palkar AV, Shrivastava MS, Padwal NJ, Padhiyar RN, Moulick N. Renal tubular acidosis due to Wilson’s disease presenting as metabolic bone disease. BMJ Case Rep. 2011;2011:bcr0420114121. doi:10.1136/bcr.04.2011.4121
  10. Kapoor N, Shetty S, Thomas N, Paul TV. Wilson’s disease: an endocrine revelation. Indian J Endocrinol Metab. 2014;18(6):855-857. doi:10.4103/2230-8210.141383
  11. Sharma S, Toppo A, Rath B, Harbhajanka A, Lalita Jyotsna P. Hemolytic anemia as a presenting feature of Wilson’s disease: a case report. Indian J Hematol Blood Transfus. 2010;26(3):101-102. doi:10.1007/s12288-010-0034-2

Reviewed by Hasan Avcu, MD, on 9/25/2022.

READ MORE ON WD