Wilson disease: A case report in primary care

What raised this nurse practitioner’s suspicion of Wilson disease in her patient? How did she manage the case?

JM, an 18-year-old female, presents to the nurse practitioner’s (NP’s) office with complaints of fatigue, nausea/vomiting, and intermittent generalized abdominal pain. She reports that these intermittent symptoms started 1-2 weeks previously and are exacerbated by eating greasy foods. JM worries that she may have a urinary tract infection because her urine looks darker than usual. She denies having fever, headache, diarrhea, or dysuria.

JM has never had sexual intercourse or been pregnant. Her menstrual cycle is irregular, ranging from 30 to 60 days. Her last menstrual period occurred 3 weeks previously. She does not take any medications and denies tobacco, alcohol, and illegal drug use. JM states that she has not traveled outside the United States and that none of her close contacts has had similar symptoms.

Her past history is notable for Epstein-Barr virus infection, mononucleosis-induced hepatitis, and elevated liver function test (LFT) results 2 years previously. Findings from ultrasonography of the liver performed at the time were unremarkable. She was referred to a gastroenterologist because of the abnormal LFT findings, but she did not follow up. 

What are the NP’s physical examination findings?

JM is well nourished; is alert and oriented to person, place, and time; and has normal vital signs. Her skin is warm and dry, but jaundiced. She has scleral icterus. Her heart and lung exam findings are normal. Auscultation of the abdomen reveals normal bowel sounds. Her abdomen is soft, with no rebound or guarding, and no organomegaly or masses. She does have slight tenderness to deep palpation in the epigastric region. Murphy’s sign is negative and she has no costovertebral angle tenderness. She has no lymphadenopathy and no peripheral edema. Based on JM’s symptoms, jaundice, and abdominal tenderness on exam, the NP refers her to the local emergency department (ED) for further evaluation.

What type of assessment and interventions are performed in the ED and during hospital admission?

Ultrasonography reveals that JM has a mildly distended gallbladder with mild to moderate sludge present. Computed tomography of the abdomen indicates gallbladder distention and some mild gallbladder wall thickening. Initial laboratory test results include white blood cells, 15.2 (high); red blood cells (RBCs), 3.43 (low); hemoglobin, 10.7 (low); hematocrit, 33.7 (low); RBC distribution width, 15.3 (high); alanine transaminase (ALT), 160 (high); aspartate transaminase (AST), 185 (high); total bilirubin, 17.4 (high); alkaline phosphatase (ALP), 42 (low normal); gamma-glutamyl transferase, 120 (high); iron, 37 (low); prothrombin time, 21.4 (high); and International Normalized Ratio, 1.9 (normal). JM is hospitalized for further evaluation. Inpatient consultations are obtained with a gastroenterologist and a general surgeon, with concern for cholecystitis.

The following morning, additional lab tests are performed. Results are ceruloplasmin level, 8 (low); RBCs, 2.65 (low); hemoglobin, 8.8 (low); hematocrit, 26.1 (low); and bilirubin, 20.9 (high). A hepatitis panel is negative. LFT values remain elevated. These results prompt concern for Wilson disease (WD), hemolytic anemia, and acute liver failure. JM is transferred to a tertiary center within 24 hours of admission and started on continuous venovenous hemofiltration and plasmapheresis. Her condition continues to deteriorate. An orthotopic liver transplantation (OLT) is performed on day 4 of the hospitalization. WD is confirmed via laboratory studies and biopsy for quantitative liver copper. JM improves slowly post-OLT and is discharged 12 days later on immunosuppressive therapy, with close follow-up. She receives genetic counseling, with screening recommended for family members.

What is Wilson disease?

Wilson disease is an autosomal recessive inherited disorder. A mutation of the ATP7B gene on chromosome 13 results in impaired copper filtration and metabolism in the liver and, in turn, copper intoxication.1 Patients with WD have excessive copper deposition in the liver, brain, eyes, and other body tissues. Without timely diagnosis and treatment, this disease is fatal in many cases.2,3 The incidence of WD is 1:50,000-100,000 live births.4 Most patients with WD first present with symptoms between the ages of 5 and 35 years.1 Because WD is uncommon and because presentation is variable and often non-specific, timely diagnosis is delayed in many cases.1

What are the clinical manifestations of WD that NPs should look for?

Presenting clinical manifestations of WD can range from being asymptomatic to having hemolytic anemia, hepatic failure, neuropsychiatric symptoms, and musculoskeletal and renal symptoms.2,5,6 Approximately 40% of patients present with hepatic symptoms, 40%-50% with neurologic symptoms, and 10% with psychiatric symptoms.7 Approximately 5% present with acute liver failure.8 A pivotal finding confirming the diagnosis is the presence of Kayser-Fleischer rings,2 which form as a result of copper deposition in the cornea and may be visible with use of a slit lamp or gonioscopy. Well-developed rings can be seen with the naked eye. Kayser-Fleischer rings are present in up to 90% of WD cases.1,2,9

Many patients with WD, including the young woman in this case, initially present with nonspecific symptoms. Patients may have symptoms of acute hepatitis, chronic liver disease, or even liver failure. Cirrhosis is a common initial presentation in up to 50% of patients with hepatic involvement.2 Psychiatric features may include behavioral, affective, schizophrenic, and cognitive-behavioral changes.2 Early neuropsychiatric symptoms include confusion, difficulty speaking, excessive salivation, and ataxia. Late neurologic manifestations are dystonia, spasticity, rigidity, and grand mal seizures. Symptomatic joint disease usually occurs late in the course of the disease. Renal manifestations include urolithiasis and hematuria.2 

What should an NP know about diagnosing and managing WD?

Early diagnosis and treatment of WD are essential to prevent irreversible tissue damage, but the wide spectrum of atypical and complex symptoms can make the diagnosis difficult and sometimes missed.1,3 Mildly abnormal LFT values may be considered an incidental finding on lab work obtained as part of a routine wellness exam. However, the finding of abnormal LFT values or liver disease of unknown origin should prompt NPs to perform a more extensive workup and to consider WD in the differential diagnosis.1 The initial workup should include a complete blood cell count, AST, ALT, ALP, total and conjugated bilirubin, albumin, serum ceruloplasmin, serum copper, 24-hour urine copper, and a slit-lamp exam for Kayser-Fleischer rings.3,5 If present, Kayser-Fleischer rings and low serum ceruloplasmin level may be sufficient to establish the diagnosis of WD.1 Liver biopsy with assessment of hepatic copper concentration is an important diagnostic component as well.

Management of WD includes lifelong use of chelating agents to remove excess copper, pharmacologic management of psychiatric and neurologic symptoms, and dietary restrictions if hepatic encephalopathy is present. Additional treatment may include rapid plasma exchange via plasmapheresis, hemofiltration, albumin dialysis, or exchange transfusion to lower circulating copper levels and reduce hemolysis.5 Liver transplantation is necessary for patients with hepatic failure. This life-saving procedure is curative for WD. Untreated WD is fatal. With timely and appropriate management, complications can be prevented, and life expectancy is similar to that of individuals without WD.5 

What are the reproductive health implications for women with WD?

Use of the copper intrauterine device (IUD) is contraindicated in women with WD.10 Because hepatic metabolism of combination hormonal contraceptives (CHCs) is significant, these agents are contraindicated in women with acute hepatitis, hepatitis with a severe flare, or cirrhosis.10 Women may use CHCs after an uncomplicated liver transplant with stable graft function for at least 6-8 months and frequent monitoring of LFT values.11,12 Safe and effective options for women with WD include non-copper IUDs and progestin-only methods. Discussion of contraception is essential for female patients of childbearing age on pharmacologic management for WD or immunosuppressive therapy post-OLT. Medications may need to be adjusted prior to and during pregnancy.

In many cases, severe acute or chronic liver disease results in anovulation and secondary amenorrhea.12 Women with WD may have excessive copper accumulation in the uterus, leading to suboptimal fertility and recurrent miscarriage.2,4 However, most women with well-managed WD can achieve a pregnancy. In general, pregnancy is considered safe for women with WD. Copper status should be optimized before pregnancy, and women should be in the maintenance phase of chelation therapy.1,13

Penicillamine, trientine, and zinc acetate are common chelating agents for WD treatment that have been used during pregnancy, although penicillamine is not advised as appropriate therapy in pregnant women with WD.14 Zinc acetate is considered a first-line choice and trientine a second-line choice in this patient population.13 Patients on chelating therapy should continue it during pregnancy, with close monitoring. Teratogenicity has been reported in animals for both penicillamine and trientine; therefore, the potential risks to the fetus associated with the selection of a particular medication must be weighed against the mother’s risk of developing acute liver failure if therapy is withheld.5 Although data are limited, a dosage reduction may be considered when possible, especially during the first trimester, when the risk for fetal teratogenicity is highest.1,8 Breastfeeding is not recommended for women on chelation therapy other than zinc acetate because of the risk of interference with the infant’s copper metabolism.1,12,15

Following OLT, many women can achieve a healthy pregnancy, although they are at high risk for anemia, pre-eclampsia, fetal growth restriction, gestational diabetes, preterm delivery, and cesarean section.11,12,16,17 Women are advised to avoid pregnancy in the first 1-2 years post-OLT, when the risk for transplant rejection is highest.1,11,17,18 In addition, delaying pregnancy for this period of time allows for stabilization of liver function and minimization of fetal exposure to high doses of immunosuppressant agents.16

Because WD is an autosomal recessive condition, both parents must carry at least one copy of the mutated gene for offspring to have the disease. Family members of the individual with WD should be offered genetic counseling to discuss screening modalities.2,3 Furthermore, couples in whom one potential parent has WD or is a carrier may want to consider screening of the other potential parent prior to pregnancy. If one parent has WD but the other parent does not have the mutated gene, offspring will be carriers but will not have WD. If both parents are carriers, offspring have a 25% chance of having WD, a 50% chance of being a carrier, and a 25% chance of being unaffected.19

Reflection for practice

Wilson disease can cause permanent and substantial tissue damage and can be fatal without timely diagnosis and management. In this case, the NP saw a patient with vague gastrointestinal symptoms, fatigue, and history of abnormal LFT values. Physical exam findings included jaundice and epigastric tenderness with no obvious cause. Prompt referral for further evaluation may have saved this young woman’s life. She required OLT and is doing well. OLT stops progression of disease, although it may not reverse any existing tissue damage. Regardless, JM continues to carry the mutated genes for WD.

JM’s current and future reproductive health needs include counseling about safe and effective contraception, discussing any pregnancy plans with both her hepatologist and obstetric care provider, and consideration of genetic screening for the potential father of a pregnancy. Although pregnancy is not contraindicated, a multidisciplinary team and collaboration among providers are essential for the best possible outcomes.


Kimberly L. Lynch is an adult nurse practitioner at Associated Physicians of Libertyville in Libertyville, Illinois, and adjunct faculty at DePaul University in Chicago, Illinois; Indiana Wesleyan University in Marion, Indiana; and Olivet Nazarene University in Bourbonnais, Illinois. The author states that she has no financial interest in or other relationship with any commercial product named in this article.



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