Hereditary tyrosinemia

Tyrosine (Tyrosine) are a non-essential amino acids the human body, mainly from the dietary intake and phenylalanine (phenylalanine) metabolism. Caused by elevated plasma tyrosine may come from a number of diseases, including: the transient neonatal Tyrosinemia (Transient tyrosinemia of the newborn, TTN), hereditary Tyrosinemia Type I ( Hereditary tyrosinemia I), Tyrosinemia type II (tyrosinemia II; also known as Richner-Hanhart syndrome), Tyrosinemia type III (tyrosinemia III). Neonatal Tyrosinemia is temporary because of tyrosine metabolism caused by the enzyme is not yet mature enough, most of them occurred in premature infants, who will be with sophisticated enzymes has been improved, there will be no sequels. Tyrosinemia Type I and II clinical completely different type of patients have liver and kidney area of the main lesion; of patients with type II have toes, palms, soles of the feet over horny situation, will there is intellectual problem.

Tyrosinemia type I is mainly due to yanhusuo acetoacetic acid amide hydrolase enzymes (fumarylacetoacetate hydrolyase, FAH) caused by the lack of. FAH makes the lack of tyrosine metabolism have been hampered, leading to acetoacetic acid amide fumarate (fumarylacetoacetate) accumulation, can not be converted into fumarate (fumarate) and acetoacetic acid (acetoacetate). Substantial accumulation of acetoacetic acid amide fumarate into succinate acyl acetone (succinylacetone; SA), exist in the patient's plasma and urine. SA caused by the accumulation of liver injury; will inhibit omega-aminolevulinic acid (omega-ALA) hydrolase role, with the sort of acute porphyria (acute intermittent porphyria) of neurological symptoms.


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. Tyrosinemia in the Americas and Europe to the incidence rate of one hundred thousandth 1/120000. Quebec, Canada and Norway, Finland, the incidence of higher, Quebec, the highest incidence of 1/1846, Norway and Finland for 1/60000.




Symptoms



Acute Tyrosinemia:

This situation will have a baby for rapid and fulminant course, if it is not treated in time, patients will be dead quickly. Usually a few weeks after birth to 6 months time attack, patients often have poor appetite, vomiting, diarrhea, abdominal distension and low blood sugar symptoms such as jaundice and ascites, who have a similar taste of cabbage; 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), secondary rickets (rickets), liver symptoms such as splenomegaly. 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? Pyronaridine alveolar rhodopsin (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.

Chronic Tyrosinemia:

Tyrosinemia with acute symptoms, similar symptoms and incidence of late, the majority of patients after one year of age at onset. Rickets, liver and kidney barrier, high blood pressure, nervous system barriers to clinical symptoms, usually around the age of 10 may be found in the liver.



Diagnosis


Prenatal care:

Such as known prior to the one-child or both parents Tyrosinemia point mutations may be the amniotic fluid cells smoking pregnant women to carry out the analysis of point mutations. SA can also be detected in amniotic fluid concentrations are too high look.

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.

Blood tests:

At present the most credible test Tyrosinemia quantitative blood and urine are in 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, patients with 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.





Treatment


Food Control:

The use of low-protein diet and with no phenylalanine and tyrosine special formula to restrict these two amino acid intake to provide enough physical capacity required for normal growth. With diet control, due to renal tubular dysfunction resulting symptoms can be fully answered almost normal. However, liver diseases and malignant tumors can not take this to have access to treatment and prevention, so when the liver severely damaged or have a tumor, the need to rely on other methods such as liver transplant, such as to improve the condition.



Liver transplant:

When the transplanted liver function, the patient's enzyme deficiency phenomenon would be improved, long-term effects than simply to better diet control. After liver transplantation can be a normal diet, no need for special restrictions. However, patients with urine testing is still out of SA, think are caused by the kidneys. After liver transplantation for renal prognosis of the long period of time remains unclear.



NTBC treatment:

2 - (2-nitro-4-trifluoromethylbenzoyl) -1,3-cyclohexanedione (NTBC) can block ρ-hydroxyphenyl pyruvic acid (ρ-hydroxyphenylpyruvate) and transformed into uric acid (homogentisate), to reduce the emergence of SA. Studies have shown NTBC can improve on clinical symptoms and biochemical abnormalities. 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.



Supportive treatment:

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.