Copyright
©The Author(s) 2021.
World J Hepatol. Jun 27, 2021; 13(6): 634-649
Published online Jun 27, 2021. doi: 10.4254/wjh.v13.i6.634
Published online Jun 27, 2021. doi: 10.4254/wjh.v13.i6.634
Table 1 Clinical manifestations
Wilson's Disease Clinical Manifestations | |
Liver | Hepatomegaly, jaundice, pain in right hypochondria, asthenia, elevation of transaminases, acute liver injury, acute liver failure, cirrhosis (compensated and decompensated), ACLF, steatosis |
Neurological | Dystonia, tremor, dysarthria, dysphagia, Parkinson, chorea |
Psychiatric | Behavioral changes, depression, anxiety, psychosis, school performance deficit, sexual disinhibition |
Eye | Kayser-Fleischer Ring, Cataract |
Hematologic | Hemolytic anemia, coagulopathy, thrombopenia |
Renal | Acute renal failure, nephrolithiasis, urolithiasis, renal tubular acidosis |
Musculoskeletal | Arthropathy, muscle weakness |
Other | Heart disease, pancreatitis, hypoparathyroidism |
Table 2 Diagnosis tests for Wilson’s disease
Test | Normal values | Wilson disease | False negative | False positive |
Ceruloplasmin | 0.2-0.4 g/L | < 0.2 g/L | Increased levels: | Low levels: |
Hepatic inflammation | Malabsorption | |||
Malnutrition | ||||
Estrogen | Aceruloplasminemia | |||
Pregnancy | Menkes’ disease | |||
Infection | Terminal liver disease | |||
Children | Nephropathy with renal protein loss | |||
Overestimation by immunological assay | Excess zinc ingestion | |||
Healthy heterozygotes WD | ||||
Non ceruloplasmin bound copper | < 0.3 μg/dL | > 10 μg/dL | Overestimation of ceruloplasmin by immunological assay | Increased levels: |
Cholestatic syndromes | ||||
Acute liver failure | ||||
Copper intoxication | ||||
Urinary copper excretion | < 0.6 μmol/24 h; < 40 μg/24 h | > 1.6 μmol/24 h; > 100 μg/24 h | Incomplete collection; Children | Increased levels: |
Cholestatic syndromes | ||||
Autoimmune hepatitis | ||||
Chronic active liver disease or hepatocellular necrosis | ||||
Healthy heterozygotes WD | ||||
Liver biopsy | < 50 μg/g; < 0.8 μmol/g | > 250 μg/g; > 4 μmol/g | Uneven copper distribution | Increased levels: |
Cholestatic syndromes | ||||
Idiopathic copper toxicosis disorders | ||||
Kayser Fleischer rings | Absence | Present: Neurological WD | Primary biliary cholangitis | |
Absence: | ||||
50% hepatic WD | ||||
Asymptomatic WD |
Table 3 Leipzig scoring for Wilson’s disease
Typical clinical signs and symptoms | |
Kayser-Fleischer ring | |
Present | 2 |
Absent | 0 |
Neurologic symptoms or typical abnormalities on MRI | |
Severe | 2 |
Mild | 1 |
Absent | 0 |
Serum ceruloplasmin | |
Normal (> 0.2 g/L) | 0 |
0.1-0-2 g/L | 1 |
< 0.1 g/L | 2 |
Coombs negative hemolytic anemia | |
Present | 1 |
Absent | 0 |
Other tests | |
Liver copper1 | |
> 4 μmol/g | 2 |
0.8-4 μmol/g | 1 |
< 0.8 μmol/g | -1 |
Rhodamine positive granules2 | 1 |
Urinary copper excretion3 | |
Normal | 0 |
1-2 times ULN | 1 |
> 2 times ULN | 2 |
5 times ULN after penicillamine | 2 |
Mutation analysis detected | |
Both chromosomes | 4 |
One chromosome | 1 |
No mutations | 0 |
Total Leipzig score | |
Score | Evaluation |
≥ 4 | Diagnosis established |
3 | Diagnosis possible |
≤ 2 | Diagnosis very unlikely |
Table 4 Monitoring urinary copper excretion in the treatment of Wilson’s disease
Treatment | Initial treatment | Maintenance treatment | Undertreatment or non-compliance | Overtreatment or non-compliance |
D penicillamine | > 500 μg/24 h | 200-500 μg/24 h | > 500 μg/24 h | < 200 μg/24 h |
Trientine | > 500 μg/24 h | 200-500 μg/24 h | > 500 μg/24 h | < 100 μg/24 h |
Zinc | > 100-500 μg/24 h | < 75 μg/24 h | > 15 μg/24 h | < 5 μg/24 h |
Table 5 Adverse effects of medical therapy used in the treatment of Wilson’s disease
Medication | Side effects |
D penicillamine | Early (1-3 wk): |
Fever, cutaneous eruptions, myelosuppression, lymphadenopathy, proteinuria | |
Late: (> 3 wk-yr) | |
Renal: Nephrotoxicity, nephrotic syndrome | |
Lungs: Goodpasture syndrome | |
Bone marrow: Aplasia | |
Eye: Optic neuritis, retinitis | |
Skin: Pemphigus, pemphigoid lesions, aphthous stomatitis, hair loss | |
Autoimmunity: Lupus erythematosus, myasthenia gravis, polymyositis, immunoglobulin A depression | |
Dose-dependent: | |
Pyridoxine deficiency | |
Mammary hypertrophy | |
Skin: Elastosis serpiginosa, lichen planus, progeria-like skin changes | |
Neurological deterioration (10%-50%) | |
Trientine | Few side effects: |
Bone marrow depression | |
Sideroblastic anemia | |
Hemorrhagic gastritis, loss of taste, and skin rash | |
Neurological deterioration is less common | |
Zinc | Very few side effects: |
Gastric irritation | |
Elevation of serum amylase and lipase | |
Bone marrow depression | |
Neurological deterioration is very uncommon | |
Tetrathiomolybdate | Few side effects: |
Bone marrow suppression | |
Increased serum aminotransferase levels | |
Anemia | |
No neurological deterioration |
- Citation: Lucena-Valera A, Perez-Palacios D, Muñoz-Hernandez R, Romero-Gómez M, Ampuero J. Wilson's disease: Revisiting an old friend. World J Hepatol 2021; 13(6): 634-649
- URL: https://www.wjgnet.com/1948-5182/full/v13/i6/634.htm
- DOI: https://dx.doi.org/10.4254/wjh.v13.i6.634