Introduction
Hepatolenticular degeneration(hepatolenticular degeneration), also known as Wilson (Wilson's disease), is an autosomal recessive copper metabolism deficiency disease, more common in adolescents, the incidence rate is about 1 / (500,000 ~ 10 million). Clinical manifestations of progressive exacerbations of vertebral system symptoms, cirrhosis, psychosis, renal dysfunction, and corneal pigment ring KF ring.
Cause
(1) Causes of the disease
Hepatolenticular degeneration is an autosomal recessive hereditary disease. The affected gene is involved in the disorder of copper metabolism, and is closely linked to the esterase D gene located on the chromosome and the retinoblastoma gene.
(two) pathogenesis
The pathogenesis of WD includes the reduction of biliary excretion, ceruloplasmin synthesis disorders, lysosomal defects, metal prion gene abnormalities and regulation of gene abnormalities. At present, most of the previous two theories have been endorsed by most scholars.
1. Copper metabolism synthesis barrier
Most laboratory experiments with 64Cu on copper metabolism in vivo have shown that serum ceruloplasmin reduction is the main reason for copper accumulation in WD. However, the lack of ceruloplasmin has not been fully elucidated. According to the ceruloplasmin electrophoresis, Bichtrrich found that the normal adult is composed of undifferentiated ceruloplasmin D, which is converted into ceruloplasmin C by peptidase in the liver, and then 80% ceruloplasmin C and 20% copper. The cyanoprotein D constitutes ceruloplasmin, while the WD patient only has ceruloplasmin D, and almost no part C, which leads to ceruloplasmin synthesis disorder.
2. Biliary copper excretion disorder
Normal adults need to absorb 2 to 5 mg of copper from food every day. After the copper ions enter the human body, most of them are firstly combined with albumin to directly react with copper, which is transported to the liver, and the various globulins in the liver cells are mainly The α2-globulin binds firmly to ceruloplasmin (indirect reaction copper). Generally, the total amount of copper in plasma is 90% to 95% in the form of ceruloplasmin. Only about 5% of copper is loosely bound to albumin, amino acids and peptides. The latter freely passes through the cell membrane and plasma copper in all organs. Except for exchange, most of the lysosomes are taken out of the feces through the bile duct, and a small amount is excreted by the urine. That is, the copper absorbed by normal people from food, in addition to the physiological needs of the body, the excess copper is mostly excreted from the bile in the bile duct. Frommer took the lead in measuring the copper content in the duodenal juice of 8 patients with WD and 10 patients in the control group. It was found that the WD group was significantly lower than the control group. It was suggested that the bile duct copper barrier was an important cause of copper accumulation in WD patients.
Copper is an essential trace element in the human body and acts as a prosthetic group to participate in the synthesis of many important biological enzymes. Normal adults take 2 to 5 mg of copper daily from the diet, about 30% of which is absorbed into the stomach at the upper end of the stomach, duodenum and jejunum. Most of them are loosely bound to albumin and enter the liver cells. In the liver cells, copper and α2 globulin are firm. Combined with ceruloplasmin (CP), CP has oxidase activity and is dark blue, and the remaining copper is bound to other special copper proteins. The daily bile discharge of normal people is about 1200 μg. About 70% of the CP is present in the plasma, and the rest is present outside the blood vessels. 90% to 95% of the copper in the blood circulation binds to the CP. CP has important physiological functions, and can be used as a donor of copper to participate in the synthesis of cytochrome C and other copper proteins. It has a ferrous oxidase function, oxidizes ferrous iron to a high-iron state, and reduces oxygen to water. The remaining copper is excreted from the body through bile, urine and sweat. In patients with WD, ceruloplasmin synthesis disorder, more than 90% of patients with serum CP decreased significantly, but the content of liver anterior ceruloplasmin (Apo-CP) and normal structure, suggesting that biochemical disorders occur in the liver Apo-CP and copper binding, CP synthesis disorders are the basic genetic defects of this disease. Intrahepatic copper metabolism disorder causes serum CP synthesis disorder, resulting in lower serum copper and CP, increased urinary copper excretion, reduced bile duct copper, excessive copper deposition in liver, brain, kidney and cornea, but about 5% of Wilson It is difficult to explain the normal serum CP levels in patients.
In recent years, it has been determined that the CP gene is located on chromosome 13 (13q14-21) and has multiple mutant types. The expression CP is a 132kD glycoprotein, which consists of 1046 amino acid residues and consists of a single polypeptide chain combined with six different types of copper ions. There was no abnormality of ceruloplasmin precursor in WD patients, and there was no change in genes and expression products. It was not possible to explain the significant decrease of SF serum CP from the genetic point of view. Gene mutations have obvious genetic heterogeneity. The mutation methods include conversion (A→G), transversion (C→G), deletion (CCC→CC) and insertion (T→TT), among which C→G transversion is the most common. The resulting amino acid changes (such as histidine to glutamic acid, aspartic acid to serine) and frameshift mutations, the mutations found so far involve the ATPase functional region. Mutations in the WD gene cause changes in the function of the P-type ATPase (also known as ATP7B). The main function of ATP7B is copper transport, partial or total loss of function, and the inability to transport excess copper ions from the cells, causing the deposition of copper ions in specific organs and tissues. Cause the disease.
There is racial difference in the molecular pathogenesis of WD. The high-frequency mutation point of ATP7B gene in European and American patients is exon 14 and is in the phosphorylation region of ATP7B gene and ATP-binding region. The mutation of two functional regions causes the function to disappear, resulting in enzyme deficiency and transport process. The medium energy causes copper ions to stay in the cells. The high-frequency mutation point exon 8 of Chinese WD patients is in the transmembrane functional region of the whole ATP7B gene, causing the primary and secondary structure changes of the protein, leading to the stagnant cell membrane copper transport and causing disease.
The pathology of WD is characterized by the deposition of large amounts of copper in tissues. The lesions are characteristically distributed in brain tissue, liver, kidney and cornea. The brain lesions are the earliest and obvious in the nucleus, followed by the globus pallidus, caudate nucleus and cerebral cortex. The subthalamic nucleus, red nucleus, substantia nigra, thalamus and dentate nucleus can also be involved. Neurons were significantly reduced or completely lost, axonal and astrocyte hyperplasia. In the elastic layer of the corneal margin and in the endothelial cytoplasm, brown yellow fine copper particles can be deposited, which can also be seen in the central cornea and interstitial cells. Liver surface and cut surface can be seen in different sizes of nodules or pseudolobules, similar to liver cirrhosis after necrosis, hepatic steatosis, containing copper particles. Electron microscopy showed dense mitochondria, disappearance of mitochondria and disruption of rough endoplasmic reticulum in hepatocytes.
symptom
Clinical manifestation
1. The disease usually occurs in childhood or adolescence. The average onset of liver symptoms is about 11 years old. The average onset of neurological symptoms is about 19 years old, and a few can be late to adulthood. Most patients have neurological symptoms first, a few have liver symptoms first, and a few patients with initial symptoms of acute hemolytic anemia, subcutaneous hemorrhage, nasal discharge, renal dysfunction and mental symptoms. The onset is slow, and a few are acutely ill due to trauma, infection, etc., and eventually there will be symptoms of liver and nerve damage.
2. The prominent nervous system manifests in this disease is extrapyramidal symptoms.
(1) tremor is a common first symptom. Starting from one hand, it starts with small tremor and gradually becomes coarse tremor. When it is free to exercise, it can be static, intentional or posture tremor, often combined with several forms of tremor. Appear, as the disease progresses, tremor can affect the limbs, head and jaw, etc.;
(2) The dysarthria is also common. The speech sound is low, vague or hoarse, slow or intermittent. When it is severe, it can not be heard. It is caused by slowing movement of the tongue, lips, throat, throat and jaw; drooling and swallowing. Difficulties are also common, caused by the rigidity of the throat muscles, the tongue muscles and the facial muscles;
(3) When dystonia affects the face and oral muscles, there is a "mask face", a bitter smile, a weird expression or an involuntary movement of the mouth and the mouth, involving limb stiffness and slow movement of the limbs and trunk, slow finger movement, flexion posture and transformation. Difficulty in posture, etc., gait abnormalities are difficult to start, stiff, and tow. Severe cases are similar to Parkinson's flustered gait, limb dance-like movements, hands and feet, and so on;
(4) can have a wide range of neurological damage, such as cerebellar damage leading to ataxia and language disorders, cone system damage, hyperreflexia, pathological reflex and pseudobulbar paralysis, hypothalamic lesions produce obesity, persistent high fever and hypertension Wait;
(5) Patients with onset before the age of 20 often have dystonia and Parkinson syndrome. Older people often show tremors, dances or throwing-like movements. The symptoms develop slowly, and they can be relieved or aggravated in stages. By.
3. Eye damage Due to the deposition of copper in the posterior corneal elastic layer, 95% to 98% of patients can see the KF corneal ring (Kayser-Fleischer corneal ring), the KF ring is located at the junction of the cornea and the sclera, and the inner surface of the cornea is greenish brown or gold. Brown, about 1.3mm wide. The vast majority are seen in both eyes. Individuals can be seen in a single eye. Patients with nervous system involvement can appear. Sometimes they need to pass through a slit lamp to detect it. In the past, sunflower cataract was considered to be advanced, but Walshe observed 15 newly diagnosed patients, 11 (73.3%) had this cataract, and a few patients had lens opacity, dark adaptation, and pupillary light response.
4. Psychiatric symptoms are seen in 10% to 51% of patients, such as mental disorders as the first or prominent symptoms are easily misdiagnosed as mental illness. Early stage may have progressive mental retardation, slow thinking, regression of academic performance, memory loss, inattention, etc., may have emotional, behavioral and personality abnormalities, emotional disorders are quite common, patients often cry for no reason, restless, irritating or The commotion, lack of interest in the surrounding environment, expressions of ignorance and indifference. If left untreated, the late stage can develop into severe dementia and hallucinogenic psychotic symptoms such as hallucinations.
5. Liver symptoms The liver is the first affected part of the disease. About 80% of patients develop liver symptoms, and most of them exhibit non-specific chronic liver disease syndrome, such as burnout, weakness, loss of appetite, liver pain, hepatomegaly or shrinkage, splenomegaly. Large and spleen hyperfunction, jaundice, ascites, spider mites, esophageal varices bleeding and hepatic coma. 10% to 30% of patients develop chronic active hepatitis, a few have asymptomatic hepatosplenomegaly, or only transaminase continues to rise without any liver symptoms. Liver damage can cause abnormal metabolism of hormones in the body, leading to endocrine disorders, delayed puberty, women with irregular menstruation, amenorrhea or a history of abortion, and male breast development. Very few patients with acute liver failure may be due to excessive transfer of copper to lysosomes in hepatocytes, causing lysosome damage, resulting in massive necrosis of hepatocytes.
6. Kidney damage Copper ions deposit in the proximal tubules and glomeruli, causing renal tubular reabsorption, renal hypoglycemia, multiple amino aciduria, phosphate urine, uric aciduria, hypercalciuria and proteinuria, etc. Patients may have renal tubular acidosis with renal failure. It can also produce osteoporosis, bone and cartilage degeneration.
7. Blood system damage Very few patients start with acute hemolytic anemia. A large amount of copper is released into the blood from necrotic hepatocytes, which is more common in adolescents, and most of them are fatal. Some patients have reduced blood cells due to hypersplenism, nose, gum bleeding and subcutaneous hemorrhage.
8. Most patients have skin pigmentation, and the face and the legs are prominent. There may be a decrease in eye regulation function, a decrease in collection ability and dark adaptation function, and arrhythmia.
The clinical manifestations of Wilson's disease are complex and diverse, often resulting in difficult diagnosis. In order to facilitate clinical diagnosis and differential diagnosis, there are literatures to summarize WD patients with different clinical manifestations, and the classification is as follows:
I. Brain type is a central symptom of central nervous system symptoms.
(1) Generalized Wilson's disease (Wilson type) The clinical features are: 1 typical hepatolenticular degeneration; 2 the age of onset is mostly ≤ 14 years; 3 muscle stiffness is heavier, showing awkward movements, speech consumption and eating Unclear, etc., tremor is light or absent; 4 childhood often has a history of jaundice, often accompanied by mild to moderate liver damage, advanced high jaundice, moderate to high ascites and severe liver damage.
(2) The torsion type is mainly characterized by muscle stiffness, but the course of disease develops rapidly. In the short term, it shows a moderate to high body torsion and paralysis state, and early limb contracture, deformity and severe language disorder. This type can also be classified as an acute progressive type of hepatolenticular degeneration.
(3) Dance hand and foot Xu type refers to the initial symptoms and main manifestations of dance movement, dance - hand and foot movement or dance hand and foot movement - dystonia. In the early stage, there are no obvious extrahepatic symptoms such as hepatic symptoms and tremors and muscle stiffness. The characteristics of this type are: 1 more than children, juvenile onset; 2 mainly manifested as eyebrows, eye-opening, twisting nose, pouting, swinging head, twisting neck and other head and face involuntary movement or / and multiple parts of the limbs twisted, dancing Such as abnormal exercise, clinical performance is similar to small chorea. Reduced muscle tone or mild lead-like increases. As the disease progresses, it is often possible to switch to a typical hepatic degeneration type.
(4) The clinical features of pseudo-sclerosing type are as follows: (1) most of the onset after 20 years old; 2 the whole body tremor mainly with positional tremor is progressively aggravated, while the muscle stiffness is lighter; 3 the liver is milder and appears later. The clinical manifestations of significant liver damage usually occur at the end of the period.
(5) Mental disorders Most types of WD patients are accompanied by symptoms such as euphoria, emotional instability, violent personality or reduced initiative during the course of the disease. The mental disorder refers to those with severe psychotic symptoms as initial symptoms or core symptoms. The main symptoms are arrogance or depression, rich hallucinations or / and delusions, such as refusal to eat, destruction, self-injury, and injury.
II. Spinal cord type and hepatic cerebrospinal type
The clinical features of the spinal cord type are: 1 mostly in the onset of 10 to 20 years old; 2 with progressive sacral paraplegia in both lower extremities, a small number of peripheral neuropathy. Most of this type is accompanied by chronic hepatic brain syndrome, which is called hepatic cerebrospinal type.
III. Bone-muscle type
Dustur first reported a group of 9 Indian-born adolescents with WD who were characterized by rickets-like skeletal changes and myopathy-like manifestations, while brain and liver symptoms were less and lighter, called bone-muscle hepatic degeneration. . There are reports of 11 Chinese patients with bone-muscle type, which have the following characteristics: 1 The age of onset is 5 to 20 years old, with an average of 11.18 years; 2 bones and joint pain, muscle weakness of the proximal extremities, muscle atrophy and other bones - Muscle symptoms are the first symptoms; 3 are less early and have neurological symptoms and liver symptoms; 4 The course of disease progresses slowly, and the average course of disease is 5 years after admission; 5 If no effective copper-discharging treatment is performed, muscle stiffness and language may occur as the disease progresses. Unclear extrapyramidal symptoms.
IV. Visceral type and brain-visceral mixed type
(1) The clinical characteristics of abdominal hepatic degeneration are: 1 mostly sudden onset before 5 to 10 years old; 2 the course progresses rapidly, and there is rapid loss of appetite, high jaundice and ascites; more than 2 to 4 weeks after onset He died of liver failure. Often misdiagnosed as fulminant hepatitis.
(2) The clinical features of liver type and brain-liver type liver type are: 1 insidious onset, slow progress; 2 manifested as loss of appetite, mild jaundice, small amount of ascites or hypersplenism; 3 laboratory examination There may be a mild to moderate increase in ALT, a decrease in total plasma protein, especially albumin reduction and ball/white inversion; 4B super-shows a special sonographic image of the liver of various liver-like degenerations. In most patients, the extra-pyramidal central nervous system symptoms appear in the above-mentioned aggravation of liver symptoms, which is called liver-brain type.
(3) Kidney type and kidney-brain type lower extremity edema, increased urinary protein, gross hematuria under the naked eye or microscopic examination as the first symptom without obvious neurological symptoms and liver symptoms are called kidney type. Patients with brain-type WD have kidney-brain type in patients with renal damage such as proteinuria, hematuria, and/or renal dysfunction during the course of the disease.
diagnosis
1. Patients with HLD who are highly suspected of having the following conditions must have a slit lamp to check for corneal KF ring and copper metabolism test.
(1) Compatriots of patients with HLD have been confirmed.
(2) Among the siblings, those who died of acute severe hepatitis (fullinant hepatitis) or other liver diseases (especially those with viral antigens negative for viral antigens).
(3) Children or adolescents with unexplained cirrhosis, transient jaundice, salivation, tremors, dance-like movements or mental disorders should be identified with HLD. If necessary, further slit lamp and copper metabolism tests should be performed.
2. Diagnostic criteria
(1) Family genetic history. Parents are close relatives, compatriots with HLD patients or those who die of unexplained liver disease.
(2) Extrapyramidal symptoms, signs and/or liver symptoms such as slow progressive tremor, muscle stiffness, and dyslexia.
(3) The KF ring was confirmed by the naked eye or slit lamp.
(4) Serum ceruloplasmin <200 mg/L.
(5) Urinary copper > 50 μg / 24h.
(6) Liver copper > 250 μg / g (dry weight).
Judgment: Anyone who has the above items (1) to (3) or (2) and (4) can be diagnosed as clinically dominant. Only those having the above items (3) to (5) or (3) to (4) are asymptomatic HLD. Only those (1), (2) or (1), (3) should be suspected of HLD.
The clinical manifestations of this disease are complex, the patient has no neurological manifestations, clinical misdiagnosis is quite common when various systemic symptoms appear, and the identification should be considered from both the liver and the nervous system.
1. Mekes disease and chronic liver disease due to severe protein deficiency, serum CP can be decreased, biliary cirrhosis can also appear KF ring, attention should be paid to identification;
2. The disease appearsParkinson's DiseaseSome signs can be differentiated from PD according to corneal KF ring, severe ataxia tremor, and serum ceruloplasmin reduction;
3. Must also be differentiated from acute or chronic hepatitis, cirrhosis, small chorea, Huntington's chorea, torsion, senile dementia, psychosis, hepatorenal syndrome, etc.
complication
In patients with hepatolenticular degeneration, the immune function is partially low. Some patients have symptoms of pseudobulbar paralysis, such as difficulty swallowing, returning to drinking water, etc., especially those who are bedridden for a long time are more likely to suffer from hypostatic pneumonia, urinary tract infection and hemorrhoids. Patients with extrapyramidal symptoms have difficulty walking and are prone to fall and have fractures. In patients with hepatolenticular degeneration, there is portal hypertension combined with esophageal and gastric varices in patients with decompensated cirrhosis. It is prone to acute upper gastrointestinal bleeding and even hemorrhagic shock. The detoxification ability of a few livers is reduced, and hepatic encephalopathy is prone to occur. , liver and kidney syndrome, etc.; some patients have seizures due to brain damage. The above-mentioned various complications often aggravate the condition, seriously affect the treatment effect, and prolong the hospitalization time of the patient. If not treated promptly and accurately, the prognosis of some patients is worse than that of patients without complications.
treatment
(a) treatment
1. Once the disease is diagnosed or the patient has a neurological sign, systemic treatment should be performed to effectively prevent the disease from developing. The sooner the treatment is, the better. Pay attention to reducing the copper content of food (<1mg / d), limiting the diet containing more copper, such as nuts, chocolate, peas, broad beans, corn, mushrooms, shells and snails, honey, animal liver and blood. High amino acid and high protein diet can promote urinary copper excretion.
2. Drug treatment includes copper-removing drugs, blocking intestinal absorption of copper and promoting copper-discharging drugs. Patients should choose a suitable drug for life-long medication. Some female patients have progressive neurological symptoms during pregnancy and no significant changes in copper metabolism. Although WD patients with copper metabolism disorders can not be completely treated, but blocking the pathological process of copper deposition, neurological signs can be improved to some extent, KF ring disappeared, liver function recovery. The copper chelating agent includes:
(1)D-penicillamine(D-penicillamine): It is the first choice to complex excess copper in the blood and tissues to be excreted from the urine. It forms a non-toxic complex with copper in the liver, eliminates the toxicity of free copper, and induces the synthesis of copper-depleting metal. Copper metallothionein. Adult dose 1.0 ~ 1.5g / d, children 20mg / (kg? d) oral, 3 times / day. The first use should be a penicillin skin test. Sometimes it takes several months to take effect, dynamic observation of serum copper metabolism levels and slit lamp examination of KF ring as a monitoring indicator of efficacy. A small number of patients have temporary exacerbations such as fever, drug eruption, leukopenia, muscle weakness and tremor, and very few serious side effects such as myelosuppression, lupus-like syndrome, and nephrotic syndrome. After the treatment is terminated, the non-toxic complex will dissociate and reproduce the toxicity. It should be explained with the patient and family members that the sudden withdrawal of the drug can aggravate the condition and often listen to the patient's medication response. Moderate and severe WD patients treated with adequate D-penicillamine, symptoms often can not be improved within weeks or months, 10% to 50% of patients with D-penicillamine after the nervous system signs will still be aggravated, important It is not possible to interrupt the medication. A sudden death of WD patients several weeks after treatment has been reported, possibly related to copper deposition in the heart conduction system. A small number of patients are prone to seizures at the beginning of treatment.
(2) Zinc agent: competition inhibits the absorption of copper in the intestine, increasing fecal copper and urinary copper excretion. Commonly used zinc agents such as zinc acetate 100 ~ 150mg / d, 3 times / day, 1 hour before meals; zinc sulfate, zinc gluconate and zinc licorice can also be used. Occasionally mild side effects such as nausea and vomiting.
(3) Potassium sulfide: copper is formed in the intestine to form insoluble copper sulfide, which inhibits copper absorption. 20 ~ 40mg orally, 3 times / day.
(4) Triethylene teramine: 1.2 g/d for adults, with small side effects, used forPenicillamineSevere toxic side effects, but the source of the drug is difficult and expensive.
(5) Other complexing agents: 1Dimercaptopropanol(BAL): Adults 2.5 to 5 mg / (kg? d), divided into 1 to 2 deep intramuscular injections. In the 1950s and 1960s, WD was treated with many side effects and is rarely used at present. 2-Dimercaptosuccinate (Na-DMS): is a bismuth-based low-toxic high-efficiency heavy metal complexing agent that can bind blood free copper. In the tissue, the copper ion is combined with the enzyme system to form a thiol compound, which is discharged through the urine. The dosage is 1g, dissolved in 10% glucose solution and 40ml slowly intravenously, 1~2 times/day, 5-7 days for a course of treatment, intermittently used several The course of treatment, copper discharge effect is better than BAL, the side effects are lighter, including gum bleeding and nasal discharge, bad breath, headache, nausea, fatigue and limb pain; 3 dimercaptopropanesulfonic acid (DMPS): detoxification similar to BAL, copper discharge The effect is stronger than BAL, and the toxicity is lower; 4ammonium tetrathiomolybdate (TM): forms a copper-containing and albumin complex in the intestinal mucosa, the latter can not be absorbed by the intestinal mucosa, excreted with feces, TM can Limit the absorption of copper in the intestinal mucosa, the dose is 20mg, 6 times / day, three times in the meal, the other three in two meals, the maximum amount can be increased to 60mg each time; excessive molybdenum may be retained in the liver, spleen and bone marrow, Can not maintain treatment with TM; fewer side effects, mainly nausea Vomiting, diarrhea and loss of appetite and so on. In most patients, neurological symptoms can be improved with a decoppering agent. In order to prevent anemia, vitamin B6 (pyridoxine) 20 mg should be taken at the same time, 3 times a day.
3. Symptomatic treatment of myotonia and tremor can be used in Antan orAmantadineThe symptoms are obviously available in the compound L-dopa; the psychotic symptoms are obviously available antipsychotic drugs, the depressive symptoms are obviously available antidepressants, and the mental retardation can be used to promote the smart drugs. Regardless of liver damage, liver protection is required, and liver tylos, inosine and vitamin C can be used.
4. Chinese medicine treatment Chinese medicine believes that the disease is liver yin deficiency, liver wind movement, available liver bean tablets No. 1 and liver bean soup, consisting of rhubarb, berberine, turmeric, money grass, Alisma and Sanqi, etc., Chinese medicine can promote Bronze discharge from bile, urine and feces is safer, but the effect of copper discharge is not as good as penicillamine and zinc. It can not achieve satisfactory results when used alone.
5. Surgical treatment of 1WD with hypersplenism, white blood cells and platelets are significantly reduced, prone to bleeding and infection, splenectomy is an important adjuvant treatment, penicillamine also reduces leukocyte and platelet side effects, such patients should be small dose or not green Moldy amine; 2 treatment of severe cases can be liver transplantation treatment, the literature reported that 2 cases of WD patients after liver transplantation, symptoms improved, KF ring disappeared, biochemical indicators returned to normal, survived 6 years and 4 years respectively. At present, the longest survival time of liver transplantation in domestic WD patients is 500 days.
6. Gene therapy is still in the experimental research stage.
(two) prognosis
If the disease is not actively treated in time, most of the illness continues, and in the advanced stage, it will die due to severe cirrhosis, liver failure or concurrent infection. The length of the disease is closely related to the age of onset, and the progress is mostly slow. The course of disease can last for several years or even thirty or forty years. The average duration of disease is 4 to 5 years, but it is not uncommon for more than 10 years. Before 1948, the cause of this disease was not effective, and the course of disease was no more than 3 to 4 years. Since the application of chemotherapy, the prognosis has improved. After chemotherapy, the neurological symptoms can be improved to some extent, but it can also recur. Some symptoms can be completely relieved for a while. The longer the neurological symptoms exist before treatment, the worse the degree of recovery. Some neurological symptoms can continue to improve after more than 2 years of treatment, but liver damage recovery is poor. The prognosis of this disease depends mainly on the morning and evening of treatment, the condition of the liver when the disease is found, and the speed of liver disease progression. Some patients can die of acute liver necrosis early. Some people think that the sooner the neurological symptoms appear, the faster the disease progresses. Others have suggested that juvenile-type drugs are worse than adults, and a group of 10 juvenile cases have been reported, with an average disease duration of 5 to 7 years. If the disease is treated early, symptoms (especially neurological symptoms) may stop developing or be relieved. Therefore, the patient's siblings should be examined early before symptoms appear, and the earlier the treatment, the better the prognosis. In the future, if you can further understand the various aspects of metabolic disorders, the efficacy will be further improved.
prevention
Prevention and treatment of this disease should be diagnosed early, and the positive balance of copper metabolism in patients should be corrected in time. Pay attention to reducing the copper content of food (<1mg / d), limiting the diet containing more copper, such as nuts, chocolate, peas, broad beans, corn, mushrooms, shells and snails, honey, animal liver and blood. High amino acid and high protein diet can promote urinary copper excretion.
Determination of serum ceruloplasmin, serum copper, urinary copper, and copper content of dermal fibroblasts in vitro in family members of patients with WD can help to find homozygous and heterozygous WD symptoms before the symptoms, and the homozygotes can be treated early. Heterozygotes should be contraindicated to marry heterozygotes to avoid homozygote in their offspring. If the prenatal examination is found to be homozygous, the pregnancy should be terminated to eliminate the source of the patient.
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