In an elderly patient with long-standing balance and gait issues, did the provider likely recommend checking ceruloplasmin (copper metabolism indicator) or serum copper levels?

Ceruloplasmin vs. Serum Copper for Balance and Gait Issues

The provider most likely meant ceruloplasmin, as this is the primary screening test for copper-related neurological disorders, particularly Wilson disease, which can present with balance and gait disturbances in adults. 1

Why Ceruloplasmin is the Intended Test

Primary Diagnostic Value

• Ceruloplasmin is the recommended first-line test when evaluating unexplained neurologic abnormalities in children and adults through middle age. 1
• The American Association for the Study of Liver Diseases specifically recommends that serum ceruloplasmin should be routinely measured during evaluation of unexplained neurologic symptoms. 1
• Ceruloplasmin functions as the major carrier for copper in blood, accounting for 90% of circulating copper in normal individuals. 1

Clinical Context for Balance/Gait Issues

• Wilson disease, the primary copper-related disorder causing neurological symptoms, commonly presents with movement disorders including gait disturbances. 1
• Low ceruloplasmin (<200 mg/L or <20 mg/dL) is consistent with Wilson disease, and extremely low levels (<50 mg/L or <5 mg/dL) provide strong diagnostic evidence. 1

Why Serum Copper Alone is Less Useful

Diagnostic Limitations

• Total serum copper is usually decreased in Wilson disease (proportional to decreased ceruloplasmin), making it paradoxically low in a disease of copper overload. 1
• Serum copper measurement alone cannot distinguish between copper bound to ceruloplasmin (non-toxic) and free copper (toxic). 1
• The diagnostic value comes from calculating non-ceruloplasmin-bound copper, which requires both serum copper AND ceruloplasmin measurements. 1

Measurement Challenges

• The major problem with using serum copper diagnostically is that it depends on the adequacy of methods for measuring both serum copper and ceruloplasmin. 1
• If ceruloplasmin measurement overestimates holoceruloplasmin, the estimated non-ceruloplasmin-bound copper may yield a negative number that cannot be interpreted. 1

Practical Testing Approach

Initial Workup

• Order ceruloplasmin as the primary screening test. 1
• If ceruloplasmin is low or borderline, then add serum copper to calculate free (non-ceruloplasmin-bound) copper. 1
• Consider 24-hour urinary copper excretion if ceruloplasmin is abnormal (normal <40 μg/24 hours; Wilson disease typically >100 μg/24 hours). 1, 2

Interpretation Algorithm

• Extremely low ceruloplasmin (<50 mg/L) = strong evidence for Wilson disease 1
• Modestly subnormal ceruloplasmin (50-200 mg/L) = requires further evaluation with urinary copper and possibly genetic testing 1
• Normal ceruloplasmin does NOT exclude Wilson disease, as 10-20% of patients have normal levels 1, 2

Critical Caveats

Common Pitfalls

• Approximately 20% of heterozygotes for Wilson disease have decreased ceruloplasmin but do not have the disease. 1
• Ceruloplasmin is an acute phase reactant and may be falsely elevated during inflammation or infection, potentially masking Wilson disease. 1
• Enzymatic assays measuring oxidase activity are preferred over immunologic assays, as immunologic methods may overestimate functional ceruloplasmin. 1, 3

Age Considerations

• Wilson disease typically presents before age 40-45, making it highly relevant for this elderly patient if symptoms are long-standing from earlier onset. 2
• However, copper deficiency (which also causes low ceruloplasmin) can occur at any age and should be considered in the differential. 2

Vitamin E Context

• The concurrent recommendation to check vitamin E suggests the provider is considering nutritional/metabolic causes of ataxia and gait disturbance, which makes sense alongside copper evaluation. 4