Clinical and genetic heterogeneity in Wilson disease - A review

Advithi Rangaraju, Sridhar MS, Poonam Naik

Pdf Page Numbers :- 192-197

Advithi Rangaraju^1,*, Sridhar MS² and Poonam Naik¹

¹KIMS Foundation and Research Centre, Minister Road, Secunderabad-500003, Telangana, India

²Department of Ophthalmology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad-500003, Telangana, India

*Corresponding author: Dr. Advithi Rangaraju, Ph.D., Scientist (Genetics), KIMS Foundation and Research Centre, Minister Road, Secunderabad-500003, Telangana, India. Email: advithi.rangaraju@gmail.com

Received 22 June 2015; Revised 19 August 2015; Accepted 27 August 2015; Published 5 September 2015

Citation: Advithi Rangaraju, Sridhar MS, Poonam Naik. Clinical and genetic heterogeneity in Wilson disease - A review. J Med Sci Res. 2015; 3(4):192-197. DOI: http://dx.doi.org/10.17727/JMSR.2015/3-037

Copyright: © 2015 Advithi Rangaraju, et al. Published by KIMS Foundation and Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Wilson disease (WD) is an inborn error of copper metabolism leading to its accumulation in liver, kidney and cornea. It is caused by a defective ATPase protein which is coded by ATP7B gene. It follows an autosomal recessive mode of inheritance with a prevalence of 1 in 30,000. WD shows varied clinical heterogeneity making clinical diagnosis a difficult task. The corneal Kayser-Fleischer (KF) ring is an important diagnostic criterion as it is invariably present in 95% of the WD cases.  In this review, we discussed the varied clinical manifestations of WD which makes diagnosis a challenging process. Though genetic testing is a reliable technique to confirm clinical diagnosis, genotype-phenotype correlations are yet to be established. This could be attributed to the consanguinity and ethnic variation observed in the Indian population, suggesting genetic heterogeneity leading to clinical heterogeneity making diagnosis difficult. Further, genetic studies are warranted to establish genotype-phenotype correlations which can pave way for early diagnosis and treatment. Genetic testing will help in identifying pre-symptomatic siblings and other family members of the patient who should be advised for regular follow-up. A combination of clinical and genetic studies should be considered for proper understanding of disease manifestation and for making an early clinical diagnosis of WD. 

Keywords: Wilson disease; copper metabolism; genetic testing; ATP7B gene; KF ring