Assessment of Low Ceruloplasmin with Family History of Wilson's Disease
This patient's ceruloplasmin of 0.18 g/L (in the borderline range of 0.1-0.2 g/L) combined with a first-degree family history of Wilson's disease warrants immediate further diagnostic workup, as this presentation scores at least 2 points on the Leipzig scoring system and could represent either Wilson's disease itself or heterozygous carrier status. 1
Interpretation of Laboratory Values
Your patient's results place them in a diagnostic gray zone that requires systematic evaluation:
- Ceruloplasmin 0.18 g/L: This falls in the intermediate range (0.1-0.2 g/L), scoring 1 point on the Leipzig diagnostic system 1
- Serum copper 9.9 μmol/L: This is low (normal range typically 11-24 μmol/L), but total serum copper is unreliable as most is bound to ceruloplasmin 1
- Family history: Having a mother with Wilson's disease is critical, as this is an autosomal recessive condition 2, 3
Critical Diagnostic Considerations
Low ceruloplasmin alone has only a 6% positive predictive value for Wilson's disease, making it insufficient as a standalone test 4, 5. However, the family history dramatically changes the pre-test probability. 4
Why This Level Is Concerning But Not Diagnostic
The ceruloplasmin level of 0.18 g/L could represent several scenarios:
- Wilson's disease: 15-36% of children with confirmed Wilson's disease have ceruloplasmin in the normal range 1
- Heterozygous carrier: Approximately 20% of heterozygotes (carriers with one mutated ATP7B gene) have decreased ceruloplasmin without copper overload disease 1
- Other causes: Malabsorption, protein loss, celiac disease, or other liver disease 1, 4
Importantly, ceruloplasmin is an acute phase reactant, so inflammation or estrogen use can falsely normalize levels, potentially masking Wilson's disease. 1, 6
Mandatory Next Steps
Given the family history, you must proceed with the complete diagnostic algorithm:
Immediate Testing Required
Slit-lamp ophthalmologic examination for Kayser-Fleischer rings (present in all neurologic Wilson's disease but absent in up to 50% of hepatic presentations) 1, 7
24-hour urinary copper excretion: Values >1.6 μmol/24h (>100 μg/24h) are suggestive of Wilson's disease 1, 3
Calculate non-ceruloplasmin-bound ("free") copper: Values >1.6 μmol/L are concerning for Wilson's disease 1
Liver function tests and hepatic imaging to assess for liver involvement 3
ATP7B genetic testing: This is definitive, especially given the known family history—you can test for the specific mutations found in the mother 8
Apply the Leipzig Scoring System
Based on current information 1:
- Ceruloplasmin 0.1-0.2 g/L: 1 point
- Kayser-Fleischer rings: Unknown (0 or 2 points)
- Neurologic symptoms: Unknown (0-2 points)
- Hemolytic anemia: Unknown (0 or 1 point)
A score of ≥4 establishes diagnosis, 3 indicates possible disease requiring more testing, and ≤2 makes diagnosis very unlikely. 1
Clinical Implications and Urgency
If Wilson's Disease Is Confirmed
Untreated Wilson's disease is fatal, progressing to cirrhosis, neurologic degeneration, and death. 2, 3 Treatment with D-penicillamine (starting 250 mg/day, increasing to 0.75-1.5 g/day) is highly effective when started early. 9, 7
The mortality rate in one pediatric series was 38%, primarily due to late diagnosis and treatment discontinuation. 3
If Heterozygous Carrier Status
Heterozygous carriers do not develop copper overload disease and require no treatment, only genetic counseling. 1
Common Pitfalls to Avoid
Do not rely on ceruloplasmin alone: The positive predictive value is only 5.9-6% in unselected populations, though higher with family history 4, 5
Do not dismiss normal ceruloplasmin: Up to 36% of children with Wilson's disease have normal levels 1, 6
Do not use immunologic ceruloplasmin assays exclusively: These may overestimate levels by detecting apoceruloplasmin (copper-free form) 1
Do not delay genetic testing: In a reported case, a child with ceruloplasmin 0.16 g/L was incorrectly cleared during family screening, only to be diagnosed 18 years later via genetic testing 8
Bottom Line Recommendation
Proceed immediately with slit-lamp examination, 24-hour urinary copper, free copper calculation, and ATP7B genetic testing. 1, 9, 4 Given the maternal history, genetic testing comparing your patient's mutations to the mother's known mutations will provide definitive diagnosis. 8 Do not wait for symptoms to develop, as early treatment prevents irreversible organ damage and death. 2, 3