Tyrosinemia

Introduction The tyrosine required by the human body is obtained by diet or by oxidation of phenylalanine. In addition to the supply of synthetic protein, it is also a precursor of substances such as dopamine, adrenaline and melanin, and excess tyrosine is degraded by it. The pathway is broken down into carbon dioxide and water. Defects in the enzymes of each step in its metabolic pathway can lead to a variety of diseases with different clinical manifestations. About 30% of premature babies and 10% of full-term neonates are not mature enough due to the development of liver 4-hydroxyphenylpyruvate dioxygenase, which may cause temporary high tyrosinemia, usually in reducing dietary protein content to each 1.5 g/kg per day and disappeared after several weeks of vitamin C administration. Severe liver disease often causes tyrosine metabolism disorders due to impaired tyrosine aminotransferase, 4-hydroxyphenylpyruvate dioxygenase and urinary acid oxidase.

Cause

The disease is caused by the lack of fumarate acetoacetate hydrolase (FAH) in liver and kidney tissues. The coding gene of FAH is located at 15q23~q25 and contains 14 exons, which are about 30-50 Kb long. In the absence of enzymes, maleic acetoacetic acid, fumaric acetoacetate, and succinylacetone and succinylacetoacetate produced by their alternative metabolic pathways accumulate. The latter two combined with the SH group of protein may be the main cause of liver and kidney function damage. FAH deficiency also reduces the activity of 4-hydroxyphenylpyruvate dioxygenase (pHPPD) in the tyrosine metabolic pathway, resulting in increased tyrosine in the blood and a large amount of p-hydroxyphenylpyruvate and its derivatives in the urine. The mechanism by which this happens is unclear.

The abnormal accumulation of succinylacetone in children also strongly inhibits the activity of -amino--ketovalerate dehydrase (-ALA dehydrase), affecting the anabolic metabolism of porphyrins, and allowing children to discharge large amounts of in urine. -Amino-gamma ketovaleric acid (-ALA) with clinical signs of interstitial porphyria. The activity of -amino--ketovalerate dehydratase in liver cells and red blood cells of these children is significantly reduced, and the accumulated succinylacetone also affects cell growth, immune function and renal tubular transport function.

an examination

Related inspection

Serum tyrosine salivary casein

The clinical symptoms of this disease are easily confused with symptoms such as fructose intolerance, fructose-l,6-diphosphatase deficiency, galactosemia, glycogen accumulation disease and infant viral hepatitis. Quantification of succinylacetone in urine and determination of fumarate acetoacetate hydrolase activity in liver biopsy tissue, red blood cells or lymphocytes.

Examination may have high amino acidemia, such as tyrosine, proline, threonine and phenylalanine, liver function abnormalities, hypoglycemia, low serum protein and bleeding tendency.

Differential diagnosis

The clinical symptoms of this disease are easily confused with symptoms such as fructose intolerance, fructose-l,6-diphosphatase deficiency, galactosemia, glycogen accumulation disease and infant viral hepatitis. Quantification of succinylacetone in urine and determination of fumarate acetoacetate hydrolase activity in liver biopsy tissue, red blood cells or lymphocytes can be used as a basis for diagnosis.

Many countries and regions have carried out neonatal screening for this disease. In the past, Guthrie method was used to measure tyrosine in blood. Because the diagnostic threshold is not easy to determine, the false positive rate is very high, so it is also detected in the sample. - The concentration of fetal globulin or succinylacetone is used to assist the diagnosis. In recent years, a method of replacing the activity of -ALA dehydratase with a blood drop paper has been used.

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