What Is The Hepatolenticular Degeneration?
What is hepatolenticular degeneration?
Hepatolenticular degeneration, also known as Wilson's disease, is an autosomal recessive genetic disease.
This disease can cause abnormal metabolism of copper in the body, resulting in reduced excretion of copper from the biliary tract or disorder of ceruloplasmin synthesis, resulting in excessive copper in the body. The excessive copper salt can be deposited in liver, brain, kidney, cornea and skin, causing tissue damage in liver, brain, kidney and others. The most common are liver damage and nervous system damage.
If it is diagnosed and treated in time, the disease can be well controlled, but if it is not diagnosed and treated in time, it can cause disability or death.
Is hepatolenticular degeneration common?
Hepatolenticular degeneration is a rare genetic disease with an incidence of 1/100,000–1/30,000 worldwide and 1/90 of the carriers of the pathogenic genes. The incidence is slightly higher in the Chinese population. They are usually found and diagnosed by presenting obvious symptoms during adolescence.
What Is The Cause Of Hepatolenticular Degeneration?
What causes hepatolenticular degeneration?
Hepatolenticular degeneration is a result of cellular copper transport defect caused by mutation of ATP7B gene encoding liver copper transporter on chromosome 13, resulting in the accumulation of copper in the liver and other tissues (including brain).
Will hepatolenticular degeneration be inherited?
Hepatolenticular degeneration is an autosomal recessive genetic disease; it does not occur when there is only one causative gene; The disease occurs when a disease-causing gene is passed on from both parents.
The characteristics of autosomal recessive genetic disease is:
- Patients and genotype normal people get married, give birth to children are normal.
- The patient marries a "normal person" carrying a disease-causing gene and gives birth to a child with a 50% chance of getting sick.
- Two "normal people" carrying the disease-causing gene marry and give birth to a child with a 25% chance of getting sick.
- If two patients get married, 100% of the children they give birth to are ill, and the chances of getting sick for boys and girls are equal.
What Is The Symptoms Of Hepatolenticular Degeneration?
What damage does hepatolenticular degeneration cause to the body? What are its clinical manifestations?
Hepatolenticular degeneration leads to the inability of copper excretion from the body. Excessive copper in the body can be deposited in the liver, brain, kidney and cornea, causing damage to the corresponding organs. The main performance are:
- Liver: large liver, spleen, and jaundice. Blood tests showed elevated transaminases in liver function. Some patients may suffer from liver cirrhosis, esophageal varices caused by liver cirrhosis, or fulminant liver failure, hemolytic anemia, etc. Symptoms of the liver are most common in pediatric patients.
- Neurological symptoms: abnormal physical activity, such as involuntary tremors, gait instability, or motor incoordination. There may also be unclear pronunciation, drooling and dysphagia.
- Cornea: Copper ions can be deposited on the posterior edge of the cornea to form a circle of pigment deposition, called K-F ring, which is the manifestation of the comparative characteristics of hepatolenticular degeneration, and can be used as the important evidence for doctors to diagnose hepatolenticular degeneration.
- In addition, copper ions will also be deposited in red blood cells, kidney, joints, muscles, resulting in anemia, lower limb edema, hematuria, joint pain, muscle atrophy, muscle weakness and other symptoms.
How To Check The Hepatolenticular Degeneration?
What tests should be done for the diagnosis of hepatolenticular degeneration?
Hepatolenticular degeneration can be suspected in patients with otherwise unexplained liver dysfunction, neurological impairment, especially in families with identical and similar patients, especially those with confirmed hepatolenticular degeneration.
- Ophthalmic examination: K-F ring formed by deposition of copper ions in the cornea is a very characteristic manifestation of hepatolenticular degeneration, which can occur in about 85% of patients. For patients who suspect this disease, an ophthalmic slit lamp examination can be performed to see if there is a K-F ring.
- Blood tests serum ceruloplasmin, patients with serum ceruloplasmin will be significantly reduced.
- Urine is collected for 24 hours and examined for copper, which in patients with this disease is markedly elevated. In addition, urine copper examination is also an important basis for guiding medication in the treatment process.
- Blood tests of liver and kidney function, to see if patients have liver function, renal function damage.
- Brain CT or brain magnetic resonance imaging can check the brain for lesions.
- When the diagnosis is difficult, gene detection, liver puncture, and the like may be considered.
How To Prevent The Hepatolenticular Degeneration?
Can hepatolenticular degeneration be prevented?
Hepatolenticular degeneration is an autosomal recessive genetic disorder that is predisposed to consanguinity. Therefore, avoiding consanguinity could theoretically avoid hepatolenticular degeneration.
With the development of medicine and social progress, consanguinity has become rare. Why does hepatolenticular degeneration occur? The reason is that two couples who do not have relatives have a very small probability of carrying the disease-causing genes at the same time. The two disease-causing genes put together may lead to hepatolenticular degeneration, a situation that cannot be avoided by manpower and cannot be prevented.
Hepatolenticular degeneration, however, is not terminal and, if diagnosed early and treated with early copper removal, generally affects less quality of life and survival.
Can a prenatal examination detect hepatolenticular degeneration?
Hepatolenticular degeneration is not an item that must be screened in prenatal examination. If parents or close relatives have the disease and are very worried about the disease in their offspring, we need to comprehensively evaluate the genotyping of the parents before deciding whether the fetus needs to be tested.
Amniotic fluid aspiration cytology is commonly used for fetal detection, but amniocentesis has the risk of increased abortion, and the advantages and disadvantages must be fully weighed before the examination.
How To Treat The Hepatolenticular Degeneration?
What department should patients with hepatolenticular degeneration visit?
Department of hepatology or gastroenterology, neurology, pediatrics, etc.
How to treat hepatolenticular degeneration?
Dietary restriction alone is not enough to treat hepatolenticular degeneration, and patients need lifetime medication to promote copper ion metabolism and reduce copper ion absorption.
The most commonly use treatment is oral penicillamine, in addition can also be oral tetrathiomolybdate, oral zinc preparation, also can intravenous dimercaptopropanesulfonic acid, etc. Patients with different clinical manifestations are suitable for different drug treatments, and patients should choose the appropriate drugs under the guidance of the doctor.
In addition, patients with liver cirrhosis and liver failure can undergo liver transplantation.
Does hepatolenticular degeneration need to take medicine for life? What happens if the drug is stopped?
In addition to patients who have undergone liver transplantation, patients with hepatolenticular degeneration need lifelong medication because the disease is a genetic defect and there is no way to improve the gene, so drugs can be used to help patients to metabolize copper ions to maintain the normal function of the body.
If the condition improves and the drug is stopped, the copper ions in the body will be re-deposited, resulting in organ damage, and the already combined copper ions may be re-released, causing toxic effects and aggravating the symptoms. Irregular drug use may lead to progression, disability, or death.
Can the damage to the body caused by hepatolenticular degeneration be restored through treatment?
With the deepening of treatment, the patients' nervous system abnormalities, mental abnormalities and liver abnormalities will gradually improve, and the liver biochemical test results can usually return to normal. However, it is unclear whether the patient's risk of developing hepatocellular carcinoma increases.
What Should Patients With Hepatolenticular Degeneration Pay Attention To In Life?
What should patients with hepatolenticular degeneration pay attention to in their diet?
During the initial stage of treatment, patients should avoid consuming copper-rich foods, especially shellfish, nuts, chocolate, mushrooms, and viscera. The copper content of natural drinking water may be detected or appropriate filters may be used to remove trace elements. For patients with copper plumbing in the home, it is recommended to flush the plumbing before cooking or drinking with water.
Once the treatment is ongoing and the patient is well, moderate amounts of copper may also be acceptable.
Can patients with hepatolenticular degeneration become pregnant?
Pregnancy can also occur in patients with hepatolenticular degeneration.
Pregnancy appears to be safe for patients treated with penicillamine and triamcinolone, but it is recommended that the dose during the first trimester of pregnancy be reduced to 30% to 50% of the pre-pregnancy dose because both drugs are known to be teratogenic in animal models and to interfere with wound healing if cesarean section or perineum incision is required.
Cases have been reported that zinc may be a safer and more effective alternative, but treatment experience is limited.