|Year : 2007 | Volume
| Issue : 4 | Page : 255-258
Wilson's disease: A study of 21 cases from north-west India
Ashok Panagariya, Rajender Kumar Sureka, Anjani Kumar Sharma, Amit Dev, Neeraj Agarwal
Department of Neurology, SMS Medical College and Attached Hospitals, Jaipur - 302004, India
7, Raj Niketan, Moti Doongri Road, Jaipur - 302 004
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Wilson's disease is an inborn error of copper metabolism, which is potentially treatable. This prospective study reports 21 cases of Wilson's disease from north-west India having various clinical, biochemical and radiological features. The study highlights that the juvenile forms showed predominantly dystonic features with high frequency of seizures, while elderly group of patients showed predominantly cerebellar features. The absence of family history and relative lack of previous hepatic involvement may lead to the delay in diagnosis.
Keywords: Ceruloplasmin, copper, Wilson′s disease
|How to cite this article:|
Panagariya A, Sureka RK, Sharma AK, Dev A, Agarwal N. Wilson's disease: A study of 21 cases from north-west India. Ann Indian Acad Neurol 2007;10:255-8
|How to cite this URL:|
Panagariya A, Sureka RK, Sharma AK, Dev A, Agarwal N. Wilson's disease: A study of 21 cases from north-west India. Ann Indian Acad Neurol [serial online] 2007 [cited 2020 Sep 28];10:255-8. Available from: http://www.annalsofian.org/text.asp?2007/10/4/255/37819
| Introduction|| |
Wilson's disease (WD) is a rare inherited autosomal recessive inborn error of copper metabolism characterized by toxic accumulation of copper in liver, brain, cornea and other tissues.  It occurs worldwide with an estimated prevalence ranging from one in 30,000 to one in 100,000 (with CNS involvement in 50% cases), but it is perhaps more commonly found in India. , At present, it has evolved from a uniformly fatal disease to a potentially treatable condition. Our understanding of the disease has progressed from the clinical description to biochemical and histological aspects and finally to the genetic basis of copper metabolism. A number of aspects make the disease particularly interesting and important for neurologists, gastroenterologists and pediatricians because of the drastically varied clinical presentation that leads to diagnostic difficulties.  Early neurological symptoms of Wilson's disease include not only Parkinsonian features but also manifestations such as cerebellar ataxia, epilepsy and Young onset dementia.  Here, we report the prospective study of 21 patients with WD. The aim was to study the clinical, biochemical and radiological profile of the disease in the north-west part of our country.
| Case Series|| |
In this study, 21 patients with WD presented to our super specialty centre in North-West India from January 2000- July 2006. All the patients were subjected to a detailed clinical history, physical and neurological examination as per the standard protocol prepared by us. The past history of hepatic or psychiatric illness and family history of similar illness was taken in all patients. An ophthalmologic examination for the presence of Keyser-Fleischer ring (KF) was carried out by the examination with naked eye and slit lamp. Routine blood counts, liver function tests and estimations of serum copper, serum ceruloplasmin and 24-h urinary copper excretion were performed. The diagnosis was based on the following: ,
- History and clinical features suggestive of Wilson's disease.
- Presence of Kayser-Fleischer ring More Details by slit-lamp examination.
- Increased 24-h urinary copper excretion (>100 mg/24 h).
- Decreased serum ceruloplasmin level (<20 mg/dl).
- Decreased serum copper level (<75 mg/dl).
Patients fulfilling the criteria 1-3 plus one or more criteria out of 4 and 5 were included. Neuroimaging (MRI/CT scan of brain) was performed for all the cases and EEG was performed wherever it was indicated.
There have been number of series and case reports from Western part of world; however, limited reports are available from the Indian literature. Wadia and Dastur (in 1963 and 1968) were the earliest to describe this disease from India. Subsequently, few more reports have been published from various parts of country; ,,,, however, this is the first series of Wilson's disease from the North-Western part of the country.
| Discussion|| |
In present series, the mean age of onset was 13.2 years; earlier, similar observations regarding the age of onset had been made in Eastern India  and Turkey.  However, other series of studies have documented a later age of onset from Great Britain  and Central India.  The cause of early age of onset in the present series and Eastern India remains largely unexplained; however, presumably, unrecognized environmental factors or habit of cooking food in copper utensils (in 40% of our cases) may be implicated as the triggering events for this illness. Male preponderance (67%) was observed in the present study, which has earlier been documented in the Indian literature. , The mean delay in diagnosis was 25.2 months in the present series whereas this delay was noted to be 12.8 months in a study from western world.  The long delay may be due to the illiteracy and ignorance of the patients along with absence of positive family history and the history of jaundice, which was recorded only in 2 (9%) and 3 (14.2%) patients in the abovementioned cases, respectively. The symptoms with which these patients approached to us are shown in [Table - 1]. The clinical spectrum included tremors (85.7%), speech abnormality (76.2%), dystonia (57.1%), high mental function abnormality (57.5%), seizures (38%) and cerebellar signs (31.7%). Among these, cerebellar signs were observed in 60% of adult group cases, while juvenile group had a preponderance of extrapyramidal syndrome in combination with seizures and cognitive deficits, which was followed by dystonia and dyskinesia. In an earlier study conducted in Central India, a similar observation was made.  However, in the series from Eastern India, the dystonic variety was more frequent (96%) in the juvenile group. Apart from the commonly encountered extrapyramidal or cerebellar syndromes, world literature reveals some unusual features such as hyper-somnolence,  circling seizures,  disturbance of circadian rhythm  and optic neuropathy. The biochemical parameters studied in our study are shown in [Table - 2], which reveals that 24-h urinary copper was more than 100 mg/24 h in all the cases; moreover, low serum ceruloplasmin and copper levels were observed in 18 and 12 patients. All the patients exhibited Kayser-Fleischer ring on slit-lamp examination.
The cranial imaging morphology in Wilson's disease has been published from Great Britain  showing abnormal findings in basal ganglia (86%), thalamus (54%), brainstem (77%), cerebral atrophy (59%) and cerebellar atrophy (50%); however, in the present series, the abnormal findings on neuroimaging, as displayed in [Table - 3], was observed in the basal ganglia (66%), thalamus (33.3%) [Figure - 1],[Figure - 2], brainstem (38%) [Figure - 3],[Figure - 4], cerebral atrophy (23.6%) and cerebellar atrophy (50%). In one patient, multiple hypodense lesions in cerebral hemisphere were documented as previously reported from Eastern India.  Although the correlation between the clinical severity of Wilson's disease and extent of neuroimaging findings is controversial, the extensive lesions may correlate well with clinical severity. Most of the studies suggest a good clinicoradiologic correlation. We found basal ganglia hyperintensities in patients with dystonic, choreic symptoms and dilatation of frontal horns in patients with cognitive deficits. Patients with the late onset of disease had cerebellar atrophy. Five symptomatic patients had normal imaging. Overall, a fair correlation between the radiological findings and the clinical symptoms was observed.
All the patients were treated with penicillamine (500 mg/day in divided doses) along with vitamin B 6 (40 mg/day) and zinc acetate (elemental zinc 75-150 mg/day) with proper dietary advice to avoid copper containing food and utensils. The symptomatic treatment for dystonia, dyskinesia and seizures was given as and when required. All the patients were followed up for 2 years. Approximately 67% (14 cases) of patients reported improvement within 4-6 weeks of treatment, while 33% (seven cases) patients showed initial deterioration, for which the drug had to be withheld temporarily. Later, when the drug was administered again, 19% (four cases) improved while 14% (three cases) did not respond to the treatment. In two cases, owing to the occurrence of pancytopenia and skin rashes, the drug had to be discontinued.
| Conclusions|| |
This series of Wilson's disease from North-West India highlights that the disease is not that rare in India and has varied clinical presentations. The juvenile forms showed dystonic features with high frequency of seizures, while the elderly group of patient showed predominantly cerebellar features. The absence of family history and relative lack of previous hepatic involvement may lead to the delay in diagnosis. Early and correct diagnosis can prevent devastating consequences as the disease is treatable.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3]