Is Wilson disease a cause of peripheral neuropathy?

Wilson Disease and Peripheral Neuropathy

Wilson disease can cause peripheral neuropathy, though it is not among the most common neurological manifestations of the disease. While Wilson disease primarily affects the liver and central nervous system, peripheral nervous system involvement can occur both as a direct consequence of copper accumulation and as a complication of treatment.

Neurological Manifestations of Wilson Disease

Wilson disease presents with a wide spectrum of neurological manifestations, primarily affecting the central nervous system. According to the European Association for the Study of the Liver (EASL) guidelines, the most common neurological presentations include 1:

• Akinetic-rigid syndrome similar to Parkinson's disease
• Pseudosclerosis dominated by tremor
• Ataxia
• Dystonic syndrome

The characteristic neurological features often involve:

• Coarse, irregular proximal "wing beating" tremor
• Dystonia (focal, segmental, or generalized)
• Dysarthria (speech changes)
• Drooling
• Facial grimacing
• Difficulty controlling movement

Peripheral Neuropathy in Wilson Disease

While peripheral neuropathy is not prominently featured in the main clinical presentations described in the guidelines, evidence suggests it can occur in two contexts:

1. As a direct manifestation of Wilson disease: Copper accumulation can affect peripheral nerves, though this is less common than central nervous system involvement 2.

2. As a complication of treatment: More commonly, peripheral neuropathy develops as a consequence of copper deficiency resulting from overtreatment of Wilson disease, particularly with zinc salts and chelating agents 3, 4.

A case report documented axonal sensory motor neuropathy in a Wilson disease patient in the context of copper deficiency due to treatment with zinc and chelators 4. After treatment adjustment, only mild clinical improvement was noted during long-term follow-up, suggesting that treatment-induced neuropathy may be partially irreversible.

Monitoring and Prevention

To prevent treatment-related peripheral neuropathy, patients with Wilson disease should be:

• Closely monitored during treatment, especially when receiving zinc salts 3
• Regularly evaluated with complete blood counts, which may provide early detection of copper deficiency before neurological damage occurs 3
• Assessed for new neurological signs not consistent with typical Wilson disease manifestations

Clinical Implications

Healthcare providers should:

1. Consider Wilson disease in the differential diagnosis of patients with peripheral neuropathy, especially when accompanied by liver disease or other neurological manifestations
2. Be vigilant for signs of peripheral neuropathy in Wilson disease patients undergoing treatment
3. Promptly recognize and address any signs of copper deficiency to prevent irreversible neurological damage

Treatment Considerations

When peripheral neuropathy is identified in a Wilson disease patient:

• Evaluate copper status to determine if it's due to copper excess or deficiency
• Adjust treatment regimens if neuropathy appears to be treatment-related
• Consider treatment options with potentially fewer neurological side effects, such as tetrathiomolybdate salts or CNS-penetrable trientine 5

Early diagnosis and appropriate management of Wilson disease are crucial to prevent both copper toxicity-related and treatment-related neurological complications.