Hepatolenticular Disease: Meaning, Symptoms & Treatment

Normally, the liver works by filtering out the excess copper from the body and releasing it through urine. In hepatolenticular disease, the liver loses its ability to do so. As a result, copper builds up dangerously in the liver, brain, and eyes and can cause serious health complications.

Detecting the disease early is very important because starting treatment promptly can prevent further damage. Treatment usually consists of medications to decrease copper levels or, in severe cases, a liver transplant. Without timely intervention, the disease can result in liver failure, brain injury, or even other life-threatening ailments. Given this, if there is a medical history in your family regarding hepatolenticular degeneration, it is highly recommended to see a doctor for advice. Many people with this condition, once treated properly and continuously monitored, live an active, healthy life.

Symptoms of Hepatolenticular Disease

The Symptoms of hepatolenticular degeneration can vary considerably, depending upon the location of copper accumulation in the body, often first appearing between 6 and 45 years of age. Early symptoms are usually associated with liver problems, which might include:

• Persistent tiredness and a general feeling of weakness that isn't relieved by resting.
• Yellowing of the skin and the whites of the eyes, due to liver malfunction, which is affecting bilirubin removal.
• Abdominal pain that can range from mild discomfort to severe tenderness due to liver inflammation.
• Swelling of the abdomen due to the accumulation of fluid, called ascites, and swelling of the legs from fluid retention.
• Nausea, vomiting, and decreased appetite contribute to weight loss.

As the disease progresses, with copper accumulation in the brain, neurological and psychiatric features become more apparent:

• Tremors or shaking, which may be similar to Parkinson’s disease in severity.
• Muscle stiffness and rigidity can make movements slow and difficult.
• Mumbling and unclear speech because of problems in controlling the muscles.
• Coordination and balance problems, noticeable as clumsiness, unsteady steps, and frequent falls.
• Major personality and behaviour changes, which may include mood swings, irritability, anxiety, or depression
• The diagnosis may be tricky when psychiatric symptoms such as hallucinations or confusion predominate.

In addition to these, many patients show a very distinct sign known as the Kayser-Fleischer ring. This is a coloured ring seen around the outer edge of the iris, caused by copper deposits in the cornea. This ring is a key diagnostic clue and is present in most patients with neurological symptoms.

How is Hepatolenticular Disease Diagnosed?

Diagnosis of hepatolenticular degeneration is possible with a combination of clinical examination and specialised tests since there is no single definitive test for the condition. Early and correct diagnosis is essential for the timely commencement of treatment and prevention of irreversible organ damage. Diagnosis is usually based on the recognition of symptoms, specific signs, and confirmation of copper metabolic abnormalities by laboratory tests. The following are the main diagnostic procedures applied:

Serum Ceruloplasmin Test

Ceruloplasmin is a copper-binding protein in serum. In hepatolenticular disease, levels are generally low, sometimes less than 20 mg/dL. This test alone is not fully reliable since levels may vary with other conditions and may sometimes be normal in affected patients.

24-Hour Urinary Copper Test

This test measures the amount of copper excreted in urine over 24 hours. Patients with hepatolenticular disease typically show elevated copper levels in urine, often exceeding normal limits. It helps assess copper overload when combined with other tests.

Slit-Lamp Eye Examination

The ophthalmologist uses a slit lamp to look for a Kayser-Fleischer ring, which is found in many patients with neurological symptoms: a coloured ring around the cornea due to copper deposition.

Liver Biopsy and Copper Quantification

If the results of the test are unclear or to confirm a diagnosis, a small sample of tissue may be taken from the liver to measure the exact content of copper. A liver copper level above 250 micrograms per gram of dry tissue indicates hepatolenticular disease.

Genetic Testing

Molecular genetic testing can detect the mutations in the ATP7B gene responsible for the disease. This is especially useful for screening family members of affected individuals and confirming the diagnosis.

Brain Imaging

MRI of the brain may be done to identify copper-related damage, especially in areas such as the basal ganglia and lenticular nucleus. These studies demonstrate characteristic changes that confirm the diagnosis in patients with neurological symptoms.

How is Hepatolenticular Disease Treated?

Treatment for hepatolenticular degeneration involves different methods, depending on the stage of the disease. Treatment approaches include the removal of excess copper, prevention of accumulation, symptomatic treatment, and, in severe cases, liver transplantation. Early and lifelong treatment is necessary to avoid serious complications.

Stage 1: Initial Treatment and Copper Removal

Treatment prioritises the reduction of excess copper in the body using medications known as chelating agents. Such drugs bind with copper and assist the body in excreting copper through urine:

• D-Penicillamine: Commonly used chelator, but may cause side effects such as rash, kidney issues, or worsening neurological symptoms initially. The use of this agent often requires supplementation with vitamin B6.
• Trientine: An alternative chelating agent with fewer side effects. Newer formulations, like trientine tetrahydrochloride, are more user-friendly without the need for refrigeration. This often involves a gradual increase in the dosage of chelators until copper levels decrease and symptoms start improving.

Stage 2: Maintenance Therapy to Prevent Reaccumulation

Once the levels of copper are controlled and symptoms stabilise, lower doses of chelators or zinc therapy are used to maintain safe copper levels and to prevent reaccumulation:

• Zinc therapy: Interferes with dietary copper absorption and is commonly used for maintenance or for patients with mild symptoms.
• Dietary adjustments: Avoiding high-copper foods like shellfish, nuts, liver, chocolate, and mushrooms helps reduce copper intake.

Stage 3: Symptom Management and Monitoring

As treatment continues, regular monitoring through blood and urine tests ensures copper levels remain controlled. Neurological and psychiatric symptoms also require attention:

• Supportive therapies like physical therapy consultation through physiotherapist, speech therapy, and psychiatric care may be necessary.
• Medication dosages might be adjusted based on response and side effects.

Stage 4: Advanced Disease and Liver Transplantation

In cases where the disease causes acute liver failure or irreversible liver damage (cirrhosis), liver transplantation becomes necessary:

• Liver transplant effectively cures the disease by providing a healthy liver capable of normal copper metabolism.
• Post-transplant prognosis is generally very good, with patients often returning to normal health.
• Transplant evaluation should be urgent in patients with severe liver failure related to hepatolenticular disease.

Can Hepatolenticular Disease Be Prevented?

The condition of hepatolenticular degeneration is due to inherited mutations and hence cannot be completely prevented by lifestyle or environmental modifications. However, early diagnosis and timely treatment can effectively prevent serious complications resulting from copper accumulation. Some important points regarding prevention are as follows:

• Genetic counselling: Families with a history of hepatolenticular disease should consider genetic testing and counselling. This identifies those at risk so that monitoring and early intervention may be undertaken.
• Avoiding excess copper intake: While complete avoidance of copper is impossible, reducing additional copper intake can aid management. Patients are advised to avoid foods high in copper, such as shellfish, nuts, liver, mushrooms, and chocolate.
• Awareness of environmental copper sources: Copper can enter the body unintentionally through drinking water from copper pipes, cookware, or wells with high copper content. Flushing pipes before use and testing the water is recommended.
• Lifestyle: Avoiding alcohol and hepatotoxic substances supports liver health and complements medical treatment.
• Adhering to lifelong treatment: For diagnosed patients, strict adherence to prescribed medications and regular monitoring are crucial to prevent disease progression.

Wrapping Up

Hepatolenticular degeneration is difficult to manage as it needs lifelong attention to the treatment and frequent medical check-ups. Early diagnosis followed by regular treatment immensely improves the quality of life and lowers the risks of serious complications, such as liver failure or neurological impairment. Although the costs for ongoing therapy and specialist care can add up over time, the right health insurance can help to ease the burden. Plans from providers like Niva Bupa offer comprehensive NRI health insurance options that support patients in managing their care continuously and confidently. With proper medical support, lifestyle adjustments, and financial planning, many individuals with hepatolenticular disease lead active, fulfilling lives.

FAQs

1. Can hepatolenticular disease affect other organs apart from the liver and brain?

Yes, it can also impact the kidneys, heart, bones, and eyes, causing complications like kidney stones, cardiomyopathy, arthritis, and cataracts.

2. Are there any visible physical signs besides Kayser-Fleischer rings that indicate hepatolenticular disease?

Blue discolouration of the nails and premature osteoporosis can sometimes be seen in affected individuals.

3. Is it possible for someone with hepatolenticular disease to have normal ceruloplasmin levels?

Occasionally, patients may show normal ceruloplasmin levels despite having the disease, which makes genetic testing and careful clinical evaluation important.

4. How does hepatolenticular disease affect pregnancy and fertility?

Some women may face fertility issues or have increased risks during pregnancy, so close medical monitoring is advised.