Original articleKayser–Fleischer ring in Wilson's disease: A cohort study
Introduction
Wilson's disease (WD) is a rare metabolic hereditary, autosomal recessive transmitted disorder, characterised by a hepatic bile copper excretion defect, leading to copper accumulation in different organ tissues, including the liver, nervous system, eyes and kidneys [1]. Average annual incidence is 12–29 cases per million individuals. Of those affected, 1/90 are heterozygotes. Geographically, incidence is highest in Costa Rica with 49 cases per million inhabitants [2]; and Japan with 30–35 cases [3]. In Europe, the highest frequency is seen in Sardinia [4] with 10–12 cases diagnosed per million inhabitants per year [5]. The Kayser–Fleischer ring (KF) is the most frequently observed ophthalmological manifestation.
The term KF refers to the golden-brown, golden-green, green-yellow, golden-yellow, bronze or reddish-brown colouring of the Descemet membrane in the limbic area of the cornea. KF is considered pathognomic of WD and represents a primary criteria in diagnosis of WD. It is an indicator of severe copper overload and appears correlated to the clinical presentation of the illness [6]. In fact, it is diagnosed in 90.4–100% of patients with neurological and psychological manifestations [7], [8], in 50–60% with non-neurological manifestations [9] and in only 10–40% of asymptomatic subjects [10]. A much less common ocular manifestation of WD is the so-called “sunflower cataract” [11].
In this cohort of 67 Sardinian WD patients, illness characteristics in relation to KF presence, ophthalmological picture modifications over the years, its correlation with the prescribed therapy and systemic evolution of the illness were evaluated respectively.
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Materials and methods
A total of 67 Sardinian patients affected by Wilson's disease (WD) (35 male, 32 female), aged 13–62 years (average age ± SEM 40 ± 10 years) were enrolled and treated initially at the Istituto di Clinica Medica II and subsequently at the Department of Gastroenterology at the Policlinico Universitario in Cagliari, between 1980 and January 2011.
Following the exclusion of other known causes, diagnosis of WD in each patient was based on the presence of alterations of liver function tests and/or of the
Results
The clinical features of patients are summarised in Table 1.
Illness onset occurred between the ages of 4–12 years in 14/67 patients (21%), between 13 and 34 years in 37/67 (55%), and in 16/67 (24%) it occurred at > 35 years (late onset).
Evident neurological clinical picture was observed in 21/67 (31%) patients and psychiatric manifestations in 6/67 (9%).
Analysis revealed that 44/67 (66%) WD patients presented hepatic involvement only, 17/67 (25%) hepatic and neurological involvement, and 4/67 (6%)
Discussion
The term Kayser Fleischer ring (KF) refers to the golden-brown, brown-green, green-yellow, golden-yellow, bronze or reddish-brown colouring of the Descemet membrane in the limbic area of the cornea [20].
KF presence appears correlated to the clinical presentation of the illness [21]. It is in fact diagnosable in 90.4–100% of patients with neurological and psychiatric manifestations [8], [22], in 50–60% of patients without neurological signs and in only 10–40% of asymptomatic subjects [9], [23],
Learning points
Our study highlights the peculiar characteristics of WD in the Sardinian population:
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low presence of KF
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even distribution of KF in the different age groups
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correlation between KF presence and clinical neurological manifestations of the illness and with neuro-radiological pictures studied from encephalic MRI and ECD-SPECT
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no correlation between KF regression and improvement in the neurological picture, from both a clinical and neuro-imaging profile and the hepatic picture
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KF ring regression with
Conflict of interest statement
I certify that there is no conflict of interest with any financial organisation regarding the material discussed in the manuscript.
Acknowledgements
We would like to thank Barry Mark Wheaton for his invaluable linguistic assistance.
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