Preface:
Tyrosine is a non-essential amino acids the human body, the main sources include dietary intake and phenylalanine (phenylalanine) generated by metabolic intermediate product. When elevated plasma tyrosine may be referred to as high Tyrosinemia (hypertyrosinaemia; tyrosinaemia), its causes are likely to originate in the primary metabolic error, or by other causes of liver disease caused by cause. However because of high Tyrosinemia cause liver damage, but also much of the liver caused by continued high hair Tyrosinemia, the distinction between the two is not easy.
The basis of past studies indicate that high Tyrosinemia-related enzymes have at least three ways: tyrosine amino transferase (tyrosine aminotrasferase; TAT), ρ-hydroxy - phenyl - Coke grape acid oxidase (ρ - hydroxyphenylpyruvate dioxygenase; 4HPPD) and yanhusuo acetoacetic acid amide hydrolase (fumarylacetoacetate hydrolase; FAH), which, TAT will be the lack of eyes and skin caused by high Tyrosinemia, called Tyrosinemia type II ( Tyrosinaemia type II), also known as Richner-Hanhart syndrome (Richner-Hanhart syndrome), the main features of the soles of his feet to the palm of your hand horny albino disease (palmoplantar keratosis). 4HPPD will have much of a lack of abnormal metabolic products, including ρ-hydroxy - phenyl - coke gluconic acid, ρ-hydroxy - phenyl - Coke lactic acid and ρ-hydroxy - phenyl - acetate coke, which is also known as the tyrosine hypercalciuria. The lack of FAH can cause liver and kidney lesions, called Tyrosinemia type I (Tyrosinaemia type I), also known as tyrosine disease (tyrosinosis), can be divided into two types of acute and chronic, is the the focus of articles.
Premature babies are often temporary Tyrosinemia (Trainsient neonatal tyrosinaemia), occasionally longer in full-term newborns can also be seen. This is probably the outstanding 4HPPD neonatal or temporary lack of sophisticated, high volume of phenylalanine and tyrosine intake, or caused by a lack of vitamin C. Such defects as babies grow, 4HPPD increasingly sophisticated and improved, taking vitamin C can also be passed and quickly corrected.
Etiology:
Hereditary Tyrosinemia type I is mainly due to caused by the lack of FAH. Tyrosine metabolism in the whole into fumarate (fumarate) and acetoacetic acid (acetoacetate) a total of five by the enzyme-catalyzed reaction steps:
A. formed by transglutaminase ρ-hydroxyphenyl pyruvic acid (ρ-hydroxyphenylpyruvate).
B. three carbon containing branched-chain oxidation and simultaneously transfer and decarboxylation and the formation of uric acid (homogentisate).
C. will be oxidized into uric acid and maleic acid amide alone acetoacetic acid (maleylacetoacetate).
D. will be maleic acid acetoacetic acid amide single line into the role of heterogeneous yanhusuo acetoacetic acid amide (fumarylacetoacetate).
E. will yanhusuo acetoacetic acid amide hydrolase into yanhusuo acid and acetoacetic acid.
FAH participated in the fifth reaction. When the lack of FAH, the entire tyrosine metabolism will be hindered, making yanhusuo acetoacetic acid amide will be substantial accumulation of single-amide maleic acid acetoacetic acid may also be affected by the cumulative in the body, resulting in liver and kidney damage. These metabolites will be to restore (reduce) and go carboxylation (decarboxylate) into amber acetone (succinylacetone; SA), and gathered in the patient's plasma and urine. Therefore, the examination of patients in vivo SA concentration, the diagnosis can be used as high an important basis for Tyrosinemia. In addition, because of metabolism of the suspension may also be caused by ρ-hydroxyphenyl pyruvic acid and its derivatives accumulated in the body.
Genetic model:
Currently known human FAH gene is located in the first 15 pairs of chromosomes on the long arm (15q23-q25), belong to autosomal recessive genetic. Liver cells of patients with DNA sequence sequencing analysis showed that 34 gene mutation point and the lack of FAH.
Classification (type):
1. Acute high Tyrosinemia:
This situation will have a baby for rapid and fulminant course, if it is not treated in time, patients will be dead quickly. Attack is usually at 1-6 months old when the sick are often loss of appetite, vomiting, diarrhea, abdominal distension and symptoms of low blood sugar, etc., and may cause growth retardation, anxiety, fever and hepatomegaly phenomenon, at the same time there will be melena, hematemesis, hematuria, and the performance of congestion, such as hemolysis, and then lead to renal tubular dysfunction (renal tubular dysfunction). Happen because of liver disease, the sick began to emerge rickets (rickets), symptoms such as hepatosplenomegaly. Some patients have neurological diseases and low-tension phenomenon. These neurological diseases may be accompanied by more serious complications, such as sometimes similar to acute intermittent porphyria pyrrole alveolar (acute intermittent porphyria) of symptoms, nerve lesions caused by muscle weakness disease and high blood pressure. As the disease intensifies, jaundice, edema, abdominal effusion, lethargy, coma, liver failure and even death of such a phenomenon will happen.
2. Chronic Tyrosinemia:
The majority of chronic high Tyrosinemia in One of the children after the age of only developed symptoms. Growth retardation, gastrointestinal symptoms, sexual cirrhosis, multiple renal defects and rickets are clinical performance. Early in the disease may only be elevated tyrosine, while the later will show methionine (methionine) increased. Usually before the age of 10 at death, autopsies often visible liver tumor.
Diagnosis:
1. Antenatal check-up:
(1) such as the parents are known to cause high Tyrosinemia point mutations may be the amniotic fluid cells smoking pregnant women to carry out the analysis of point mutations.
(2) can also detect the concentration of SA in amniotic fluid to see if too high.
(3) pregnant women to take the chorionic or amniotic fluid cells, to cultivate proliferation. To be charged after a certain number of cells, measuring the activity of FAH cells to see if there is a lack of FAH phenomenon.
2. Blood tests:
Tyrosinemia is currently the most high credibility test are quantitative blood and urine of SA and its pre-chemokine concentration. Although the sensitivity of this approach, but there is still a small number of patients with low concentrations of SA at this time, it is necessary to detect the FAH activity in cultured cells as a secondary diagnosis. By the impact of genetic variability, a healthy individual cultured cells may also appear low activity FAH phenomenon. Similarly, the patient's liver samples may also be because cell culture gene back when (reversed) case, which was highly active in the illusion of FAH. Therefore, FAH enzyme activity as a diagnostic test only when the reference, not only as a diagnostic credentials.
In addition to the concentration of SA can be used as high Tyrosinemia diagnostic tools, some biochemical aspects of detection may also apply to patients in general. For example: the concentration of serum tyrosine will increase, but the concentration of methionine was not significantly improved. Urine ρ-hydroxy - phenyl - coke gluconic acid, ρ-hydroxy - phenyl - Coke lactic acid and ρ-hydroxy - phenyl - acetate concentration of coke will improve. When renal tubular damage, the Labor Department will show Fanconi Syndrome (Fanconi syndrome), which means in the urine has high levels of amino acids, glucose and phosphate. When the liver cell damage, and affect the generation of protein will also be some variety of chemical and biological performance, can be used as a basis for diagnosis. For example: vitamin K-dependent coagulation factors in acute illness is very high concentrations, while the chronic patients the concentration of the body is not normal. Vis-à-vis other liver enzyme activity, the patients in vivo γ-Glutamyltransferase activity will improve. α-fetoprotein concentrations in vivo in acute patients has increased significantly, but in chronic patients showed normal concentrations.
Treatment:
1.NTBC treatment (NTBC treament):
NTBC (2 - (2-nitro-4-trifluoro-methylbenzoyl) -1,3-cyclo-hexanedione) are good 4HPPD inhibitor, can block ρ-hydroxyphenyl pyruvic acid into uric acid and reduce the emergence of SA , is the latest for the treatment of high Tyrosinemia method. According to the report show: sick every day at oral 0.6 mg / kg NTBC, apart from a ρ-hydroxyphenyl pyruvic acid and tyrosine concentrations will increase, other biochemical abnormalities will become normal, and clinical symptoms will be dramatically improved. NTBC can also be used for treatment of this and similar neurological pyrrole rhodopsin alveolar symptoms. Because of the concentration of tyrosine due to the use of NTBC to increase, therefore, diet control are necessary.
Long-term use of the NTBC study has been discussed, especially with NTBC the incidence of liver cancer among relevance, the current can not be determined. The sooner the use of NTBC, the serious anomaly appears more difficult. So far, NTBC No side effects were reported.
2. Liver transplant (Liver Transplantation):
Handling stolen goods in liver transplant to treat the first type of high Tyrosinemia about 10 years of development time, because this type of patients will have severe liver damage, so when the recipient can have the provider of the liver the normal performance of the enzyme missing the phenomenon of patients will be improved, blood and urine in abnormal metabolites will disappear. Access to liver transplant patients can be normal after the diet, does not require special control of tyrosine and phenylalanine intake. In spite of this, the patient urine concentrations of SA and there will still be increased, presumably because of the problem caused by the kidneys. Liver transplant kidneys after long-term prognosis remains unclear.
3. Diet (Dietary treament):
Diet control are the first for the treatment of high Tyrosinemia method, the concept is to limit the tyrosine and phenylalanine intake so low that only the body can grow normally required. This food must come from a special formula, mainly the use of protein hydrolysates or without tyrosine and phenylalanine of the amino acid mixture, then add very small amounts of natural protein to supplement the appropriate tyrosine and phenylalanine. When a patient separately on tyrosine and phenylalanine intake daily to maintain at 15-20 mg / kg, the in vivo concentration of SA would be difficult to be detected. With diet control, due to renal tubular dysfunction resulting symptoms almost completely revert back to normal. However, liver diseases and malignant tumors can not take this to have access to treatment and prevention, so when the liver tumor severely damaged or elections, such as needed by other methods such as the liver transplant to improve conditions.
4. Supportive treatment (Supportive treament):
For patients with acute disease, the supportive treatment is necessary. Patients often lack the potassium ions and phosphate, therefore, necessary to add the right amount of timely. In addition, coagulation factors, calcium, albumin, phosphate, electrolytes and acid-base balance are required under close monitoring and correction. When patients in the acute attack, the tyrosine and phenylalanine intake must be reduced to at least as far as possible. Increase in vitamin D can be used to treat rickets; patients if there is infection, infection control and immediately required to be addressed.
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