A Challenging Case of Wilson's Disease: Neurological Symptoms Leading to Diagnosis

Wilson's disease (WD), first described in 1912, is a genetic disorder that affects copper metabolism. This inherited condition, caused by mutations in the ATP7B gene, disrupts the body's ability to properly transport copper. As a result, copper accumulates in various organs, particularly the liver, brain, and cornea, leading to a range of symptoms.

While WD is often associated with liver dysfunction, approximately 40% to 50% of patients initially present with neurological symptoms. These can include dysarthria, gait abnormalities, ataxia, dystonia, tremor, parkinsonism, and drooling. The age of onset can vary, but it is generally considered to be before the age of 40.

The Importance of Early Diagnosis

Recognizing WD early is crucial for effective treatment and preventing irreversible damage. However, the diversity of clinical presentations can make diagnosis challenging. To address these challenges, the Leipzig score was developed in 2003. This diagnostic tool helps to improve accuracy by systematically evaluating clinical, laboratory, and imaging findings.

The Leipzig score takes into account several factors, including Kayser-Fleischer rings (copper deposits in the cornea), neurological symptoms, liver biopsy results (total liver copper levels), and laboratory parameters (serum and urine copper levels, serum ceruloplasmin, hemolytic anemia, and genetic testing).

A Case Report: From Possible WD to Diagnosis

This case report highlights the challenges of diagnosing WD when neurological symptoms are the primary presentation. A 38-year-old male patient was admitted with complaints of imbalance, gait disturbance, weakness in the legs, speech impairment, tremors in the hands, syncope, and drooling. These symptoms had been gradually increasing over the past 8 years, and previous diagnoses of epilepsy had not resulted in improvement.

Neurological Findings and Imaging

Neurological examination revealed a range of impairments, including impaired recent memory, weakened judgment and abstract thought, dysarthria, hypophonia, muscle weakness, myoclonic jerks, tremors, dysmetria, dysdiadochokinesis, bradykinesia, masked face, postural instability, and drooling.

Magnetic resonance imaging (MRI) revealed hyperintensities in the globus pallidus, at the bilateral basal ganglia, particularly in FLAIR, T1, and T2 sequences. These findings were compatible with the known MRI patterns in WD, where hyperintensities are commonly observed in the putamen (45–85%), globus pallidus, mesencephalon, and pons.

The Role of the Leipzig Score

Initially, the patient's laboratory investigations revealed low serum ceruloplasmin levels and normal 24-hour urine copper levels. Based on these findings, the Leipzig score indicated 'possible WD' with a total of three points. Further investigations were deemed necessary.

Confirmation of Diagnosis

A D-penicillamine challenge test and ATP7B gene analysis were performed. While the genetic analysis was negative, the 24-hour urine copper levels significantly increased after the D-penicillamine challenge, exceeding the upper limit by more than five times. The Leipzig score was recalculated, and a diagnosis of WD was established with a total score of five.

Treatment and Management

Following the diagnosis, the patient was started on Trientine chelation therapy and Zinc supportive therapy. A low copper diet was also implemented.

Conclusion

This case highlights the importance of considering WD, even in the absence of classic diagnostic features such as Kayser-Fleischer rings or high 24-hour urine copper levels. The Leipzig score provides a valuable tool for assessing the likelihood of WD and guiding further investigations. Early diagnosis and prompt treatment are essential for managing WD effectively and preventing long-term complications.

It is crucial to distinguish WD in patients with young-onset movement disorder and neurological symptoms. The presence of these symptoms, along with other clinical and laboratory findings, should prompt careful consideration of WD and prompt appropriate testing and management.

Moving Forward: Understanding the Impact of WD

The complex nature of WD and the potential for neurological involvement underscore the importance of ongoing research and awareness. Continued efforts to understand the underlying mechanisms of WD and develop more effective treatment strategies are crucial for improving the lives of individuals affected by this disease.