What is the diagnosis for a patient with hypercupremia (elevated copper levels) and myoclonus (involuntary muscle jerks)?

From the Guidelines

Elevated copper levels and myoclonus are highly suggestive of Wilson's disease, and prompt evaluation by a neurologist and hepatologist is essential to initiate treatment and prevent further complications. The diagnosis of Wilson's disease should be considered in any individual with liver abnormalities or neurological movement disorders of uncertain cause, as stated in the EASL clinical practice guidelines 1.

Key Considerations

• Wilson's disease is an autosomal recessive disorder affecting copper metabolism, causing copper accumulation in the liver, brain, and other tissues.
• The presence of Kayser-Fleischer rings, low serum ceruloplasmin level, and basal 24-hour urinary excretion of copper >1.6 μmol are typical findings in symptomatic patients 1.
• Neurologic evaluation and imaging of the brain, preferably by MR imaging, should be considered prior to treatment in all patients with neurologic Wilson’s disease 1.
• Myoclonus can be managed with anticonvulsants like levetiracetam (500-1500 mg twice daily) or clonazepam (0.5-2 mg three times daily), as suggested by the European Resuscitation Council and European Society of Intensive Care Medicine guidelines 1.

Treatment Approach

• Initial treatment typically includes chelation therapy with D-penicillamine (starting at 250-500 mg/day, gradually increasing to 1000-1500 mg/day) or trientine (1000-2000 mg/day in divided doses), along with zinc acetate (50 mg three times daily) to block copper absorption.
• Pyridoxine (vitamin B6, 25 mg daily) should be added when using D-penicillamine to prevent deficiency.
• Dietary copper restriction is also important, avoiding foods like liver, shellfish, chocolate, nuts, and mushrooms.

Monitoring and Follow-up

• Regular monitoring of copper levels, liver function, and neurological symptoms is essential, with treatment typically continuing lifelong.
• Family members should be screened as well, as early detection in asymptomatic relatives can prevent disease progression 1.

From the FDA Drug Label

The diagnosis, if suspected on the basis of family or individual history or physical examination, can be confirmed if the plasma copper-protein ceruloplasmin** is less than 20 mg/dL and either a quantitative determination in a liver biopsy specimen shows an abnormally high concentration of copper (greater than 250 mcg/g dry weight) or Kayser-Fleischer rings are present Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal-recessive defect that leads to an accumulation of copper far in excess of metabolic requirements The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread

Elevated copper levels are associated with Wilson's disease, which can cause neurological symptoms, including myoclonus.

• The diagnosis of Wilson's disease can be confirmed by low plasma copper-protein ceruloplasmin and high copper concentration in liver biopsy or presence of Kayser-Fleischer rings.
• Myoclonus is not explicitly mentioned in the provided drug labels as a symptom of Wilson's disease, but it can be a neurological symptom associated with the disease.
• Treatment of Wilson's disease with penicillamine or zinc acetate aims to reduce copper accumulation and promote its excretion 2, 3.

From the Research

Elevated Copper Levels and Myoclonus Diagnosis

• Elevated copper levels are associated with Wilson's disease, a genetic disorder that causes copper accumulation in the body 4, 5, 6, 7, 8.
• Myoclonus, a neurological symptom characterized by sudden, involuntary muscle jerks, can be a manifestation of Wilson's disease 4, 5, 7, 8.
• Treatment of Wilson's disease typically involves the use of anti-copper agents, such as penicillamine, trientine, and zinc salts, to reduce copper levels and prevent long-term complications 4, 5, 6, 7, 8.
• The choice of treatment depends on various factors, including the patient's symptoms, medical history, and potential side effects of the medications 4, 5, 6, 7, 8.
• Studies have shown that zinc salts, such as zinc acetate, are effective in controlling copper levels and toxicity in Wilson's disease, with a lower risk of adverse effects compared to other anti-copper agents 6, 7, 8.
• In patients with neurological symptoms, such as myoclonus, zinc salts may be a preferred treatment option due to their safer profile and potential for improved neurological outcomes 7, 8.
• Regular monitoring of copper levels, liver enzymes, and neurological symptoms is essential to ensure effective treatment and prevent complications in patients with Wilson's disease 4, 5, 6, 7, 8.