From the Guidelines
Yes, acute Wilson's disease and hereditary hemochromatosis can be diagnosed.
Diagnostic Criteria for Wilson's Disease
The diagnosis of Wilson's disease is based on a combination of clinical, laboratory, and genetic findings, including:
- Low serum ceruloplasmin levels 1
- High serum and urinary copper levels 1
- Hepatic copper measurement 1
- Presence of Kayser-Fleischer rings 1
- Acute liver failure or hemolysis 1
Diagnostic Criteria for Hereditary Hemochromatosis
The diagnosis of hereditary hemochromatosis is based on a combination of genetic and phenotypic criteria, including:
- Genetic testing for HFE gene mutations (C282Y and H63D) 1
- Elevated serum ferritin levels (>200 µg/mL) 1
- Elevated transferrin saturation (>55%) 1
- Liver biopsy to measure hepatic iron concentration 1
Key Features of Acute Presentations
Acute presentations of Wilson's disease and hereditary hemochromatosis can manifest as:
- Fulminant liver failure 1
- Acute hemolysis 1
- Rapid deterioration of liver function 1 It is essential to consider these conditions in the differential diagnosis of acute liver failure or hemolysis, particularly in young patients 1. Early diagnosis and treatment are critical to prevent mortality and morbidity associated with these conditions 1.
From the FDA Drug Label
The diagnosis, if suspected on the basis of family or individual history or physical examination, can be confirmed if the plasma copper-protein ceruloplasmin** is less than 20 mg/dL and either a quantitative determination in a liver biopsy specimen shows an abnormally high concentration of copper (greater than 250 mcg/g dry weight) or Kayser-Fleischer rings are present
The diagnosis of Wilson's disease can be confirmed through a combination of:
- Low plasma copper-protein ceruloplasmin levels (< 20 mg/dL)
- High copper concentration in liver biopsy specimen (> 250 mcg/g dry weight)
- Presence of Kayser-Fleischer rings However, hereditary hemochromatosis diagnosis is not mentioned in the provided drug labels. 2
From the Research
Diagnosis of Acute Wilson's Disease
- Acute Wilson's disease can be diagnosed based on a combination of clinical features and findings, including increased urinary copper excretion, reduced levels of serum ceruloplasmin, high concentrations of copper in liver tissues, and Kayser-Fleischer rings 3.
- Genetic studies are also becoming available for clinical use, but the utility of direct mutation analysis is limited 3.
- In some cases, diagnosis can be made by demonstrating ATP7B variants, or by the presence of Kayser-Fleischer rings and Coombs-negative hemolytic anemia 4.
Diagnosis of Hereditary Hemochromatosis
- Hereditary hemochromatosis (HH) is caused by inappropriate absorption of dietary iron, typically as the result of a specific mutation, C282Y, in the HFE gene 5.
- Diagnosis of HH is not explicitly discussed in the provided studies, but it is mentioned that early diagnosis is critical for preventing manifestations of the disease 5.
Diagnostic Challenges
- Predictions of mortality in Wilson disease with acute liver failure (WDALF) vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable 4.
- Several prognostic models have been compared, including the King's College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, and others, with varying degrees of accuracy 4.
Clinical Manifestations
- Wilson disease can present with a range of clinical manifestations, including hepatic, haemolytic, neurologic, and psychiatric diseases 3, 6.
- Hereditary hemochromatosis can cause end-organ disease from iron accumulation, including progressive damage of the liver, pancreas, skin, heart, and pituitary 5.