Correct Answer: B. Serum ceruloplasmin
The clinical presentation—jaundice, tremors, behavioral changes, hepatosplenomegaly, and pathognomonic Kayser-Fleischer rings—is classic for Wilson's disease (hepatolenticular degeneration), an autosomal recessive disorder of copper metabolism. The definitive diagnostic test is serum ceruloplasmin, which is markedly reduced (<20 mg/dL; normal 20–40 mg/dL) in >95% of symptomatic Wilson's disease cases. Ceruloplasmin is the primary copper-carrying protein synthesized by the liver; its deficiency leads to free copper accumulation in the brain (basal ganglia, causing tremors and rigidity), cornea (Kayser-Fleischer rings), and liver (cirrhosis). In Indian populations, Wilson's disease prevalence is ~1–2 per million, but consanguinity increases risk. Serum ceruloplasmin is the first-line screening test because it is rapid, widely available, inexpensive, and highly sensitive in symptomatic disease. While genetic testing confirms the diagnosis, it is not the definitive screening test and is reserved for confirmation or asymptomatic family members. Urinary copper and hepatic copper concentration are supportive but not diagnostic alone.
Why the other options are wrong
A. Genetic testing for ATP7B mutation — Although ATP7B mutation is the molecular basis of Wilson's disease and confirms diagnosis, genetic testing is expensive, time-consuming, and not the first-line diagnostic test in symptomatic patients. It is reserved for confirmation in borderline cases or screening asymptomatic siblings. NBE trap: students confuse 'definitive diagnosis' (genetic confirmation) with 'definitive screening test' (ceruloplasmin). C. Urinary copper — Elevated 24-hour urinary copper (>100 μg/day; normal <30 μg/day) is seen in Wilson's disease and supports diagnosis, but it is not the primary screening test. Urinary copper can be elevated in other cholestatic conditions and is less specific. It is used as a supportive test alongside ceruloplasmin, not as the definitive initial diagnostic tool. D. Hepatic parenchymal copper concentration — Hepatic copper concentration (>250 μg/g dry weight) is the gold standard for confirming copper overload but requires liver biopsy—an invasive procedure with morbidity risk. It is not practical as a first-line diagnostic test in a symptomatic adolescent. Serum ceruloplasmin achieves diagnosis non-invasively with >95% sensitivity in symptomatic disease.
High-Yield Facts
- Serum ceruloplasmin <20 mg/dL (normal 20–40 mg/dL) is present in >95% of symptomatic Wilson's disease and is the first-line screening test.
- Kayser-Fleischer rings (greenish-brown deposits in Descemet's membrane) are pathognomonic for Wilson's disease and appear when serum ceruloplasmin is severely low.
- ATP7B gene mutation causes defective copper-transporting ATPase, preventing biliary copper excretion and leading to toxic accumulation in brain and liver.
- 24-hour urinary copper >100 μg/day supports Wilson's diagnosis but is less sensitive than ceruloplasmin in early disease.
- Hepatic copper >250 μg/g dry weight on liver biopsy is diagnostic but invasive; reserved for borderline ceruloplasmin cases.
Mnemonics
Wilson's Diagnostic Triad Ceruloplasmin LOW + Kayser-Fleischer rings + Neuropsychiatric/hepatic symptoms = Wilson's disease. Ceruloplasmin is the screening test; rings confirm it. Copper Metabolism Pathway (ABCD) ATP7B gene → Biliary excretion → Ceruloplasmin (carries copper) → Deficiency = Wilson's. Low ceruloplasmin = copper trapped in tissues.
NBE Trap
NBE pairs "definitive diagnosis" with genetic testing to trap students who conflate molecular confirmation with clinical screening. In symptomatic Wilson's disease, serum ceruloplasmin is the definitive screening test; genetic testing is confirmatory and reserved for borderline or asymptomatic cases.
Clinical Pearl
In Indian pediatric practice, Wilson's disease often presents in adolescence with acute hepatitis or neuropsychiatric symptoms mimicking schizophrenia. A single serum ceruloplasmin level (<20 mg/dL) combined with slit-lamp examination for Kayser-Fleischer rings clinches diagnosis within hours, allowing early penicillamine or zinc therapy to prevent irreversible neurological damage.
_Reference: Robbins Ch. 18 (Metabolic Disorders); Harrison Ch. 356 (Wilson's Disease); KD Tripathi Ch. 35 (Trace Elements and Enzymes)_