Urinary copper excretion <100 microgram/di Symptomatic pts. of Wilson disease invariably have urine copper levels > 100 pg per day. Wilson disease is an autosomal recessive disorder caused by mutation in the ATP 7B gene (a copper transpoing ATPase) Diagnosis - The gold standard for diagnosis is Liver biopsy with quantitative copper assayQ. Other diagnostic tests used are ? - Serum ceruloplasmin levelQ - KF rings(2 - Urine copper excretiono - DNA Helpful-ye analysisQ Serum copper values have no diagnostic value, since they may be low, normal or elevated depending upon the stage of evolution of disease. Table : Useful Diagnostic Tests for Wilson Disease Test Normal Value Wilson Disease Serum 180-350 mg/L ceruloplasmin (18-35 mg/d1) * Low in 85% * Present in 99% KF rings Absent - If neurologic or psychiatric symptoms present. * Present in 30-50% - in hepatic presentation and presymptomatic state * Urinary copper excretion is increased 24-h urine Cu 0.3-0.8 mmol - >1.6intn ol(>100mg) in symptomatic patients * 0.9 to > mmol (60 to > 100 mg) - in presymptomatic patients Liver Cu 0.3 -- 0.8 mmol/g * Liver copper is increased (20-50 mg) tissue * > 3.1 mmol (200 mg) Haplotype analysis 0 Matches 2 Matches Treatment Zinc is the treatment of choice for Wilson diseaseQ. It produces a negative copper balance - By blocking intestinal absorption of copper - By inducing hepatic metallothionein synthesis which sequesters additional toxic copper. Table : Recommended Anticopper Treatments for Wilson Disease Disease Status First Choice Second Choice Initial hepatic manifestations Zinc Trientine and zinc Trientine and zinc Hepatic transplantation Trientine Penicillainine and zinc Hepatic transplantation Trientine and zinc * Hepatitis or cirrhosis without decompensation * Hepatitis or Cirrhosis with decompensation - Mild - Moderate - Severe Initial neurologic/psychiatric Tetraioinolybdate and zinc Trientine and zinc Maintenance therapy Zinc Trientine Presymptomatic therapy Zinc Trientine Pediatric Zinc Trientine Pregnant Zinc Trientine