From the Guidelines
Low ceruloplasmin levels should prompt a comprehensive evaluation for Wilson's disease, including 24-hour urine copper testing, liver function tests, and possibly a liver biopsy or genetic testing, as the condition can lead to severe morbidity and mortality if left untreated. According to the European Association for the Study of the Liver (EASL) clinical practice guidelines 1, a low serum ceruloplasmin level should be taken as evidence for the diagnosis of Wilson's disease, but borderline levels require further evaluation. The guidelines also recommend that Wilson's disease should be considered in any individual with liver abnormalities or neurological movement disorders of uncertain cause 1.
Some key points to consider in the evaluation of low ceruloplasmin levels include:
- 24-hour urinary excretion of copper >1.6 μmol is typical in symptomatic patients, but in children with mild hepatic disease, basal 24-hour urinary excretion of copper can only be mildly elevated or may even be in the normal range 1
- Hepatic parenchymal copper content >4 μmol/g dry weight provides critical diagnostic information and should be obtained in cases where the diagnosis is not straightforward and in younger patients 1
- Mutation analysis with specific allelic probes or by whole-gene sequencing is currently possible and available, and specific testing for known mutations or haplotype analysis should be the primary mode for screening of first-degree relatives of patients with Wilson's disease 1
Treatment for Wilson's disease typically involves copper-chelating medications such as penicillamine, trientine, or zinc acetate, which must be taken lifelong 1. Dietary modifications to reduce copper intake are also recommended, including avoiding copper-rich foods like liver, shellfish, chocolate, nuts, and mushrooms. Regular monitoring of copper levels and liver function is essential to prevent serious complications like liver failure, neurological damage, or psychiatric symptoms. Early diagnosis and treatment are crucial to improve quality of life and prevent morbidity and mortality associated with Wilson's disease.
From the Research
Low Ceruloplasmin Levels
- Low serum ceruloplasmin levels can occur in patients without Wilson's disease (WD) liver disorders, as documented in a study published in the Journal of clinical and experimental hepatology 2.
- A total of 122 (4.0%) patients without WD had serum ceruloplasmin levels less than the lower limit of normal, with a mean age of 44 ± 14 years, and 80 (66%) were men.
- Approximately one half (65/122,53%) had underlying viral hepatitis (52% hepatitis B and 48% hepatitis C).
Association with Wilson's Disease
- Wilson's disease is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of a copper transporting P-type ATPase encoded on chromosome 13 3.
- The laboratory diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper content, and elevated hepatic copper concentration.
- Copper chelation with penicillamine is an effective therapy in most patients and hepatic transplantation is curative in individuals presenting with irreversible liver failure.
Diagnostic Thresholds
- Urinary copper excretion higher than 100 μg/24 h is useful for diagnosing Wilson's disease, and a d-penicillamine challenge test may produce higher levels than 1400 μg/24 h, allowing for better diagnostic accuracy 4.
- In children, the optimal cut-off value of 24-hour urinary copper levels to identify Wilson's disease was 70 mcg, with a sensitivity and specificity of 81.8% and 89.8%, respectively 5.
- When the serum ceruloplasmin level was < 20 mg/dl and the 24-h urinary excretion of Cu was >70 mcg, the sensitivity was 75.8%, and the specificity was 97.7%.