A very early Presentation of Wilson disease

Wilson disease should be included in the differential diagnosis for patients with abnormal liver function tests, chronic hepatitis, cirrhosis, or acute liver failure [1,2]. The spectrum of presentation also includes isolated neuropsychiatric symptoms and asymptomatic patients. Some patients present with a combination of hepatic and extrahepatic symptoms. A non-immune hemolytic anemia is common in patients with acute liver failure caused by Wilson disease, but it may also occur in the absence of acute liver failure. The rates of organ-specific manifestations at the time of presentation vary widely, as following [3-6]: 

1- Liver disease: 18 - 84 %

2- Neurologic symptoms: 18 – 73 %

3- Psychiatric symptoms: 10 - 100 %

Furthermore, patients usually develop organ-specific manifestations as the disease progresses (eg, patients who present with liver disease may subsequently develop neurologic or psychiatric symptoms and vice versa)

Male patient, aged 13 years, Yemeni, developed recurrent monthly attacks of fever (39-40 C), upper abdominal pain, nausea, vomiting and occasional diarrhea. Each attack had lasted for 5-7 days, for which recurrent hospital admissions were done with conservative treatment (IV fluids, Ranitidine, Hyoscine, Metronidazole). In between these attacks, the patient was completely asymptomatic. During the last 3 attacks, he developed associated arthritis of the Left ankle & Right elbow that partially resolved spontaneously with the attacks. His routine laboratory tests during these attacks revealed mild elevation of liver enzymes and bilirubin associated with moderate leukopenia and thrombocytopenia (Tables 1,2). His Abdomen US was unremarkable. General examination revealed only irregular pulse with some dropped beats. ECG revealed only slightly irregular rhythm. There was no a definite diagnosis. A list of DD was considered including viral hepatitis, Malaria, FMF, porphyria, autoimmune disorders, cyclical neutropenia,….etc.

Recurrent acute self-limiting hepatitis can be a serious early presentation of Wilson disease. Cupper studies are usually inconclusive in such earlier cases. However, the diagnosis should be still considered and a therapeutic test of D-Penicillamine can be helpfully tried, based on the clinical suspicion together with regular follow-up of cupper studies. At a certain time later on, the diagnosis can be confirmed. 

1- Viral markers: negative.

2- Markers of auto-immune hepatitis: negative.

3- Cupper studies:

1. Normal results but after some months they were abnormal.

4- Liver biopsy revealed: 

a. Hepatic focal necrosis.

b.Normal cupper content.

This patient has recurrent attacks of fever, abdominal pain, transaminitis,......etc. Collectively, this patient has recurrent similar attacks of acute & self-limited hepatitis. The approach was to search for the possible causes of acute hepatitis. All viral markers were done then autoimmune screen including ALKM, anti- smooth muscle antibodies. All were negative, even ESR was normal. There was a remaining metabolic cause for acute hepatitis. In this age, Wilson disease should be considered. Liver biopsy was done. It revealed hepatic focal necrosis. Copper content was also measured in dry hepatic tissue and it was on the upper limit of normal. Slit lamp examination for possible Kayser-Fleischer ring was done several times but there was a controversy about its presence. 

• Regarding Urinary cupper 

(Normal range is 10-30 ug/day) 

1. If > 40 ug/day  suspect the diagnosis.
2. If > 100 ug/day confirm the diagnosis.
3. All should be doubled in cholestasis. 

• Regarding cupper content in dry liver tissue 

1. It is a highly specific test for diagnosis but not sensitive.
2. Wilson disease can still be considered in normal results.
3. Total body copper scan can be used for quantification. 

D-Penicillamine was given as a therapeutic test. Helpfully, the patient didn’t develop the same attacks for 2 months. The medicine was then changed to steroids by his referring physician as the diagnosis was not yet confirmed. However, after few days, the patient developed another severe attack with the same previous picture. An expert opinion was asked and the diagnosis of Wilson disease then re-considered. Additionally, He advised to repeat cupper studies every 2 months, while the patient is off treatment (both steroid & penicillamine). After one month, the patient developed another similar attack and was re-admitted to the hospital. On repeating cupper studies, the results were significantly higher than previous ones. The patient was re- started on Penicillamine and there was no more attacks of hepatitis. Finally, the patient was diagnosed as Wison disease. For ankle & elbow arthritis, it was due to pseudogout, caused by Wilson disease. For irregular pulse, it can be due to excess cupper effect on the conductive system of the heart. For transient thrombocytopenia and leukopenia, they remained unexplained. However, some papers about Wilson disease mentioned some associations with these disorders, related to excess cupper.

1. Any patient presenting with unexplained chronic liver disease, should be considered as Wilson disease until proved otherwise. Any young patient presenting with unexplained abnormal invol- untary movements, not responding to treatment, should be con- sidered as Wilson disease until proved otherwise. These consider- ations for Wilson disease, are not due to being common but being TREATABLE, so there will be an excellent response even revers- ing of some pathologies with early treatment.
2. Common presentations of uncommon diseases is more common than uncommon presentations of common diseases. However, this case was somewhat different. He was uncommon presentation of uncommon disease.The presentations of Wilson’s disease are sometimes as following: hepatic … 40%, neuro/psychiatry ...40%, Renal ...20%.
3. The presentations of Wilson disease are sometimes as following: hepatic … 40%, neuro/psychiatry ...40%, Renal ...20%.
4. For KF ring, it is present in 100% of patients with neurological/ psychiatric presentation but in only 50% of patients with hepatic presentation. However, sometimes it needs a highly skillful ophthalmologist to detect it, as written in some textbooks.
5. Ceruloplasmin, even if increased during the acute phase, it will not be more than 30 mg/dl, in patients with Wilson disease.
6. The treatment of choice is D- Penicillamine. If intolerable, Trien- tine is the alternative. Zinc oxide and Zinc acetate are not effective treatment for Wilson disease but it should be an adjuvant therapy.

The patient was treated empirically by D-Penicillamine for the suspected diagnosis.

There was a dramatic response to the chelation therapy of Wilson’s disease. Additionally, his cupper studies turned to be positive at later times.

No funding for the case report.

There is no conflict of interest.

The patient agreed for publication and a consent was done.

1. Lorincz MT (2010) Neurologic Wilson's disease. Ann N Y Acad Sci 1184:173.
2. Poujois A, Woimant F (2018) Wilson's disease: A 2017 update. Clin Res Hepatol Gastroenterol 42: 512.
3. Taly AB, Meenakshi-Sundaram S, Sinha S, Swamy HS, Arunodaya GR (2007) Wilson disease: description of 282 patients evaluated over 3 decades. Medicine (Baltimore) 86: 112.
4. Soltanzadeh A, Soltanzadeh P, Nafissi S, Ghorbani A, Sikaroodi H, et al. (2007) Wilson's disease: a great masquerader. Eur Neurol 57: 80.
5. Asadi Pooya AA, Eslami NS, Haghighat M (2005) Wilson disease in southern Iran. Turk J Gastroenterol 16:71.
6. Moores A, Fox S, Lang A, Hirschfield GM (2012) Wilson disease: Canadian perspectives on presentation and outcomes from an adult ambulatory setting. Can J Gastroenterol 26: 333.

1. Table: Lab tests.

2. Table: Lab tests.

General examination revealed only irregular pulse with some dropped beats. ECG revealed only slightly irregular rhythm. There was no a definite diagnosis. A list of DD was considered including viral hepatitis, Malaria, FMF, porphyria, autoimmune disorders, cyclical neutropenia,….etc.

Investigations: (Tables 3-7).