Wilson disease is a condition in which the body’s ability to excrete copper is impaired. This causes an individual to become vulnerable to copper intoxication, which is characterized by excessive levels of free copper in the bloodstream.
“Unbound copper that is not ceruloplasmin-bound is released into the bloodstream by the liver,” Dutta and colleagues wrote in the Journal of Current Medical Research and Opinion. “In the kidneys, eyes, and brain in particular, this free copper precipitates throughout the body.”
Wilson disease is universally fatal if left untreated. In the United States, diagnostic tools are available in most healthcare facilities; the biggest impediment to a diagnosis is therefore the insidious ways in which the disease can mask itself. The presentation of a patient with Wilson disease can be highly heterogeneous and vague.
Read more about Wilson disease etiology
In poorer countries, diagnostic tests may not be available even if physicians suspect a diagnosis of Wilson disease. This is especially true for imaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT).
In F1000 Research, Adhikari and colleagues presented a case study of a patient in Nepal who was diagnosed with Wilson disease.
“Nepal is a low-income country in South Asia, and a full chronic liver disease screening (including tests for Wilson’s disease, autoimmune hepatitis, hemochromatosis) is usually not possible in the Nepali health setup,” they wrote. “The limited screen includes alcohol history, history of any drug or toxin use and serologies for hepatitis B and C.”
The authors of the study argued that liver function tests can go a long way in helping physicians confirm their suspicion of Wilson disease.
Case Report: Liver Failure and Wilson Disease
The case as presented details a 36-year-old female who presented at the emergency department with shortness of breath for the last 10 days. She also reported abdominal distension and the yellowish discoloration of her skin for the past 2 months. There was no history of fever, abdominal pain, nausea, vomiting, or altered bowel movements.
The patient revealed that she has been consuming home-made alcohol almost daily for the past 12 years. She could not provide an estimate of the amount of alcohol consumed. The patient was seen at another healthcare provider 3 weeks ago for a case of alcoholic liver disease. She stopped consuming alcohol but her symptoms did not improve.
Upon examination, the patient appeared to be pale and icteric. Her vital signs indicated blood pressure of 90/60 mm Hg, heart rate of 78 beats/min, respiratory rate of 20 breaths/min, temperature of 98.7oF, and oxygen saturation of 97% at room temperature.
The patient’s abdomen was distended but non-tender; liver and spleen were non-palpable but shifting dullness was positive. Chest examination revealed reduced air entry; neurological examination was normal. Bilateral pitting pedal edema was observed.
An abdominal ultrasound was conducted, revealing hepatosplenomegaly and gross ascites. An upper gastrointestinal endoscopy revealed esophageal varices, as well as mild portal hypertensive gastropathy. The patient was negative for hepatitis B and hepatitis C; a direct Coombs test was negative as well. The patient’s ALP/total bilirubin ratio was 3.09 and her AST/ALT ratio was 3.4.
A slit lamp eye examination revealed Kaiser-Fleischer rings; 24-hour urinary copper was 85.70 μg (high) and serum ceruloplasmin level was 23 mg/dl (normal).
The physicians of this patient calculated the Leipzig score for this patient, which was four: 2 for the presence of Kaiser-Fleischer rings, 1 for Coombs negative hemolytic anemia, and 1 for high 24-hour urinary copper.
The patient was thus diagnosed with Wilson disease with subacute liver failure. The patient was prescribed oral zinc acetate, as well as spironolactone, furosemide, and thiamine.
The patient was discharged a week later and continued to show improvements in subsequent follow-up visits. After 11 months, the patient’s ALP/total bilirubin ratio was recorded to be 62.5 and her AST/ALT ratio was 1.5.
From Suspicion to Diagnosis
In this case study, the patient did not present with any neurological complications of Wilson disease; her main complaints were abdominal/cardiorespiratory.
The patient’s history of consuming homemade alcohol is not unique in Nepal; according to Adhikari and colleagues, people in Nepal mostly consume homemade alcohol, which can complicate history-taking as the exact percentage of alcohol in these beverages are difficult to estimate.
Read more about Wilson disease diagnosis
“We usually ascribe liver disease in any patient to the alcohol, no matter the amount of intake by the patient, especially if serologies are nonreactive and there is no drug or toxin exposure,” they wrote. “In our patient with a history of alcohol use, we extended the tests beyond the conventional limited screen, which led to a diagnosis of Wilson’s disease.”
The liver function test in particular proved to be highly valuable, given that a combined ALP/total bilirubin ratio < 4 and an AST/ALT ratio > 2.2 has a 100% sensitivity and specificity for Wilson disease in a patient with liver disease who presents with acute liver failure. According to the authors of the study, liver function tests are readily available in even remote parts of Nepal.
After diagnosis and the initiation of treatment, this patient’s clinical condition improved tremendously. Her ALP/total bilirubin and AST/ALT ratios continued to improve and returned to normal in a matter of weeks. If her physicians did not pursue further investigations and accepted that her alcohol usage was the sole reason for her presentation, her condition would have likely deteriorated.
This study demonstrates that the challenge of diagnosing Wilson disease can often be two-fold: first, the plausibility of alternative diagnoses in explaining a patient’s symptoms; second, the lack of proper diagnostic tools in poorer regions of the world. Therefore, to arrive at a correct diagnosis of Wilson disease, physicians must be aware of Wilson disease as a possible cause for liver failure and pursue investigative measures accordingly, starting with liver function tests if other more advanced tools are unavailable.
Adhikari S, Shah PK, Sharma YR. Case report: using basic liver function tests as a guide to suspected Wilson’s disease. F1000Res. Published online July 20, 2021. doi:10.12688/f1000research.54569.2
Dutta S, Sarma SN, Gupta S, et al. Essential case report study on Wilson disease. Curr Med Res Opin. Published online September 5, 2022. doi:10.52845/CMRO/2022/5-9-2