Wilson disease is a rare autosomal recessive disorder of copper metabolism resulting from pathogenic variants in the ATP7B gene on chromosome 13(13q14.3). This gene encodes a copper transporting P type ATPase essential for biliary copper excretion and incorporation of copper into ceruloplasmin. Defective or absent ATP7B function leads to impaired biliary copper excretion and toxic accumulation of copper in the liver, brain, cornea, kidneys and other organs. The worldwide incidence is approximately 1 in 30,000 live births. The clinical spectrum of wilson disease is broad and age dependent, with hepatic manifestations being more common in children and neurological or psychiatric symptoms predominating in adults. Hepatic presentations range from asymptomatic transaminitis to acute liver failure or cirrhosis, whereas neurological features include tremor,dystonia,dysarthira and parkinsonian symptoms. Psychiatric manifestations such as personality changes, depression and behavioural disturbances may also occur. A pathognomic sign is the presence of Kayser-Fleisher(KF) rings due to copper deposition in descement membrane of cornea. Diagnosis relies on clinical suspicion supported by low serum ceruloplasmin, elevated 24 hour urinary copper excretion, increased hepatic copper content and genetic testing of ATP7B mutations. Early recognition is crucial because wilson disease is potentially fatal if untreated but fully treatable with copper chelating agents such as penicillamine or trientine and zinc therapy to reduce intestinal copper absorption in advanced cases, liver transplantation remains as the only option.

CASE PRESENTATION

11 year old male child came to our hospital with total duration of illness of around 1 year 5 months. To start with he developed drooling of saliva from mouth and developed nasal tone to his speech and not able to speak clear words which worsened gradually and some difficulty in eating. After 3 months he was not able to walk properly without support and then gradually was unable to stand  and sit without support. He also developed aggresive behaviour intermittently, abnormal laughter at times. In last 7 days he developed 1 episode of GTCS convulsion. There was no fever, involuntary movements, altered sensorium, sleep disturbances. There is a history of 1 sibling loss at 11 years of age, cause not known to parents. On general physical examination, patient was alert, cooperative and oriented. Neurological examination- some cognitive decline present, gag reflex was sluggish, dysarthria present. Cerebellar signs were positive like finger nose test, dysdiadokinesia, heel knee test, Ataxic gait seen. On abdominal examination, hepatomegaly present with liver span 12cms. Lab investigations including CBC, LFT, RFT were within normal limits, HbsAg, HCVAb were negative. Abdominal sonography revealed hepatomegaly.

As there was loss of achieved milestones, some cognitive decline, seizure, subtle cerebellar signs a possibility of neuroregression mixed type (gray matter+white matter+cerebellar) was thought of, MRI brain was done it showed signs of diffuse gyral swelling hyperintensity involving superior frontal and right temporal lobe, bilateral basal ganglia and thalamic diffusion restriction. We were planning to go for Whole exome sequencing. Suddenly we thought, because there was intact mentation, drooling of saliva, psychiatric features, we went for a slit lamp examination of eyes and K F rings came out to be present in both eyes. Then we did serum ceruloplasmin levels which came out to be low(<3mg/dl), total 24 hour urinary copper after D-penicillamine challenge test came out to be high(3862.88µg/day).

These helped in confirmation of diagnosis of Wilson disease, treatment regimen was planned as follows: restriction of copper rich food, penicillamine 250 mg twice daily and zinc tablet 50 mg once daily, levetiracetam  500mg twice daily was given and asked for regular follow up.

Fig-1:Kayser–Fleischer (KF) ring seen with naked eyes.

Fig-2: Kayser–Fleischer (KF) ring seen in slit-lamp examination.

Fig-3 & Fig-4: MRI Brain Film:Diffuse Gyral Swelling WithT2wi/Flair Hyperintencity Noted Involving Bilateral Superior Frontal Lobe And Right Temporal Lobe Without Any Diffusion Restriction.

Bilateral Diffuse Symmetrical T2wi Hyperintencity Noted In Bilateral Basal Ganglia And Bilateral Thalamic Showing Central Diffusion Restriction In Thalamic Region.

Fig-5: Serum Ceruloplasmin report –Low (<3mg/dl)

Fig-6: 24 Hour Urine Copper Report – High (3862.88µg/day)

DISCUSSION

Wilson’s disease is an autosomal recessive disorder of copper metabolism. The defect results in impaired biliary excretion of copper and its accumulation in various organs like liver, brain, cornea and kidney. 

The disease usually begins in late childhood or adolescence with hepatic / neurological or psychiatric symptoms depending on prominent site of copper deposition. 

In our case, the 11-year-old male presented with regression of achieved milestones and seizure, which is a relatively unusual manifestation of Wilson disease.

Neurological features such as nasopharyngeal weakness, dysarthria, cerebellar signs, and behavioural changes were noted at presentation. MRI brain showed involvement of frontal and temporal lobe involvement apart from basal ganglia and thalamus involvement. Due to these cognitive, behavioural, some psychiatric changes and dysarthria, ataxia, we were not able to correlate with hepatomegaly as LFT was normal so, we went for slit lamp examination which showed the presence of Kayser–Fleischer rings in both eyes which paved our path to drive on right path. Further detailed tests showed low serum ceruloplasmin levels, increased 24-hour urinary copper excretion after penicillamine challenge test which confirmed Wilson disease.

While movement disorders and dysarthria are common neurological features in Wilsons, seizure and developmental regression have been described in only limited subsets of patients likely due to cortical and subcortical copper deposition. Concomitant hepatic involvement evidenced by hepatomegaly, further supports multisystem nature of disease. Early recognition of such atypical presentation is essential as it is a potentially reversible cause of progressive neurological dysfunction in children. Mainstay of therapy involves copper chelators such as  D-penicillamine along with zinc supplementation to reduce intestinal copper absorption. Dietary restriction of copper-rich foods plays an adjunct role. Addition of levetiracetam for seizure control was appropriate in this case. This case highlights the importance of considering Wilson’s disease in any child presenting with unexplained neurological regression and new onset seizures.

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