Can Wilson's disease (hepatolenticular degeneration) present with neurological symptoms without hepatic symptoms for the first time at 40 years of age?

From the Guidelines

Yes, Wilson's disease can present with neurological symptoms without hepatic symptoms for the first time at age 40. While Wilson's disease typically manifests before age 40, late-onset cases have been documented, with some patients presenting with isolated neurological symptoms in their 40s or even later, as noted in the EASL clinical practice guidelines: Wilson's disease 1. Neurological manifestations can include tremors, dysarthria, dystonia, parkinsonism, and psychiatric disturbances, occurring without obvious liver involvement. This happens because copper accumulation can affect the brain independently of liver damage.

Key Considerations

• The diagnosis and treatment of Wilson's disease have been updated in recent guidelines, emphasizing the importance of early detection and treatment to prevent irreversible damage 1.
• The EASL clinical practice guidelines: Wilson's disease provide a comprehensive overview of the diagnosis, treatment, and management of Wilson's disease, including the presentation of neurological symptoms without hepatic symptoms 1.
• A practice guideline on Wilson disease also highlights the importance of a high index of suspicion for diagnosis, including serum ceruloplasmin measurement, 24-hour urinary copper excretion, slit-lamp examination for Kayser-Fleischer rings, and possibly brain MRI and genetic testing 1.

Diagnosis and Treatment

• Diagnosis in such cases requires a high index of suspicion and should include serum ceruloplasmin measurement, 24-hour urinary copper excretion, slit-lamp examination for Kayser-Fleischer rings, and possibly brain MRI and genetic testing.
• Treatment typically involves copper chelation therapy with D-penicillamine (initial dose 250-500 mg/day, gradually increased to 1000-1500 mg/day) or trientine (1000-2000 mg/day in divided doses), along with zinc supplementation (50 mg elemental zinc three times daily), as recommended in the guidelines 1.
• Early diagnosis and treatment are crucial even in late-onset cases to prevent irreversible neurological damage, emphasizing the need for prompt medical attention if symptoms suggestive of Wilson's disease are present, regardless of age.

From the Research

Presentation of Wilson's Disease

• Wilson's disease (WD) is a disorder of copper transport that can present with a wide range of symptoms, including hepatic, neuropsychiatric, and neurological manifestations 2.
• The disease can manifest at any age, and the symptoms of presentation may be hepatic or neuropsychiatric, with a vast range of disturbances for both groups of symptoms 2.
• Neurologic symptoms in WD appear at an older age compared to hepatic symptoms and can manifest in patients with misdiagnosed liver disease, in patients when the hepatic stage is clinically silent, or with treatment failure 3.

Neurological Symptoms without Hepatic Symptoms

• Neurological symptoms in WD can occur without hepatic symptoms, and the disease can present with neurological symptoms for the first time at an older age, including at 40 years of age 3, 4.
• The most common neurologic symptoms of WD are movement disorders, including tremor, dystonia, parkinsonism, ataxia, and chorea, which are associated with dysphagia, dysarthria, and drooling 3, 4.
• Patients with WD can have a purely neurological presentation, without hepatic symptoms, and the diagnosis can be challenging in these cases 5.

Diagnosis and Treatment

• The diagnosis of WD is based on a combination of clinical, laboratory, and genetic findings, including the presence of Kayser-Fleischer rings, low serum ceruloplasmin, and abnormal liver function tests 2, 5.
• The treatment of WD involves the use of copper chelators, such as penicillamine and trientine, and zinc salts to reduce copper overload and improve neurological symptoms 2, 6.
• Early diagnosis and treatment can prevent further damage and improve the quality of life for patients with WD 3, 6.