An Unusual Presentation of Wilson's Disease

Wilson's disease affects the metabolism of copper and is a rare hereditary disorder that is inherited autosomally recessively. The liver and brain are the main organs affected by this disorder, which causes progressive hepatolenticular degeneration. A 15-year-old male patient arrived at the outpatient department (OPD) with mild abdominal pain on the right side, and both eyes showed Kayser-Fleischer (KF) rings. An abdominal ultrasound showed that the spleen was enlarged. Copper levels in urine were found to be higher. After a liver biopsy, cirrhosis, and mild chronic active hepatitis were found. The majority of hematological indicators were normal; however, a peripheral blood smear revealed mild thrombocytopenia. Wilson's disease is uncommon, so diagnosing it requires a high degree of suspicion. In circumstances of inexplicable liver cirrhosis or isolated neurological symptoms, it could go unnoticed. The only primary complaint in the case being presented was abdominal pain. However, the age upon presentation, the existence of KF rings in both eyes, and other tests helped us get the diagnosis.


Introduction
Wilson's disease is a rare hereditary disorder affecting the metabolism of copper, inherited autosomally recessively.Neurological and hepatic impairment are the primary symptoms [1].An estimated one in 30,000 live births are affected by Wilson's disease annually, with the East Asian region having a significantly higher prevalence [2,3].Chromosome 13's ATP7B gene mutation causes an incorrect copper transport protein to be produced.This genetic defect results in an accumulation of copper in many tissues.The brain and liver are commonly involved.Neurological symptoms include changes in behavior, tremors, slurring, and drooling.Hepatic symptoms include fatigue, edema, nausea, vomiting, loss of appetite, jaundice, and easy bruising.Patients may also develop corneal Kayser-Fleischer (KF) rings.Mutations in one copy of the gene ATP7B are carriers of Wilson's disease.People with Wilson's disease have mutations in both copies of the gene [4][5][6][7].Wilson's disease carriers do not need treatment, but those who have the illness, symptoms or not, need lifelong care.

Case Presentation
A 15-year-old male patient came to the outpatient department complaining of sporadic right-sided abdominal pain.There was no history of fever, altered bowel habits, nausea or vomiting, or significant weight loss.There was no notable family history.Pallor, icterus, cyanosis, clubbing, lymphadenopathy, and edema were not present on general examination.During the examination of the abdomen, the spleen was felt halfway between the left costal border and the umbilicus indicating splenomegaly.Neurological examination was normal.Laboratory investigations and work-up for Wilson's disease were sent (Tables 1, 2).

Patient values
Normal range   The spleen measured 12.8 cm in size on abdominal ultrasound (USG).Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis showed cirrhotic changes in the liver and splenomegaly.The increased copper levels in the urine and presence of KF rings on slit lamp examination were suggestive of Wilson's disease (Figure 1)

FIGURE 1: Kayser-Fleischer ring as seen on slit lamp
The black arrow indicates the Kayser-Fleischer ring MRI brain (plain and contrast) showed multiple altered signal intensity areas in bilateral ganglio-capsular regions involving deep grey matter (Figure 2).

Discussion
Wilson's disease patients may exhibit slowly progressing cirrhosis, which is typically well compensated.
There might be a severe illness (acute liver failure) without any neurological symptoms.Measurements of the liver's copper level in conjunction with a liver biopsy may aid in the diagnosis.Once diagnosis was established, D-penicillamine therapy was initiated.Initially, D-penicillamine 250 mg once a day (OD) was started followed by 250 mg increments every four days.
Similar cases, mostly involving individuals over 40, have been reported [8,9], where the first presentation is related to the neurological system without hepatic involvement.
The mobilization of copper from the liver, which raises levels of unbound copper and exacerbates neurological symptoms, is assumed to be the cause of this deterioration.The frequency of neurological damage following penicillamine therapy has been the subject of numerous studies.While some research cast doubt on this association, others claim that rates range from 30 to 75% of patients [10,11].Improving the patient's condition is the aim of the initial phase of treatment.The first-line medications are penicillamine and trientine.Penicillamine increases urine excretion to as much as 15-45 μmol daily and chelates copper.Penicillamine may cause the neurological symptoms to worsen.Patients who are intolerant to Dpenicillamine are administered trientine.For adults, 1-3 g of D-penicillamine orally three to four times a day, one hour prior to meals is given.Children's dosage is 20 mg/kg, administered twice daily.When administered gradually, starting at a dose of 250 mg once daily and increasing by another 250 mg every four to five days until the full daily dose is reached, penicillamine is frequently better tolerated by patients.It is advised to maintain medication at this dose for at least six months because of the slow rate of improvement.One way to handle maintenance is to lower the chelator dose or replace it with zinc.Zinc restricts the absorption of copper via the gastrointestinal system by inducing intestinal metallothionein.Adults should take 50 mg of elemental zinc orally three times a day [12].If combination therapy (chelator plus zinc) is used, individuals with severe neurological manifestations or decompensated hepatic disease should be the only ones to receive it, per a specialist's recommendation.For all young adults and children with chronic liver disease who do not show any symptoms, Wilson's disease should be taken into consideration.First-degree relatives of the affected individual must undergo screening for Wilson's disease.
Wilson's disease patients usually present with hepatic symptoms at first, though neurological symptoms can potentially appear later.However, in this particular instance, pain in the abdomen was the only symptom [12].Patients should be advised not to eat foods high in copper, like shellfish, almonds, chocolate, liver, and mushrooms.
Liver transplantation is required for patients with Wilson's disease-related acute liver failure, cirrhosis, and decompensated liver disease who do not get better after two to three months of medication therapy.If neglected, Wilson's illness worsens and eventually proves fatal.The patient dying without receiving treatment and going undiagnosed is the biggest risk.Individuals who are diagnosed early and adhere strictly to their treatment plan should expect to enjoy normal lives.

Conclusions
Wilson's illness is an uncommon condition, so it is possible that the diagnosis can go unnoticed.When isolated symptoms, like abdominal pain in a young individual, are present with liver cirrhosis without a known cause, it is imperative to maintain a high index of suspicion.It is imperative that patients be counseled against stopping the treatment for Wilson's disease.Wilson's disease prevention guidelines are still lacking.However, treatment can prevent symptoms from worsening if they are detected early.

FIGURE 2 :
FIGURE 2: MRI STIR transverse section of the brain Yellow block arrows show hyperintensity in the bilateral ganglio-capsular region MRI: Magnetic resonance imaging, STIR: Short tau inversion recovery

FIGURE 3 :
FIGURE 3: Nodules of varying sizes separated by fibrous septae and inflammatory infiltrate (100 X, low power) The black arrow indicates the fibrous septae