OVERVIEW
Also known as amino acid disease and aminoaciduria, when there is neurologic involvement, there is usually only mild psychomotor retardation, with no obvious symptoms until 2 to 3 years after onset. Like other inherited metabolic disorders, amino acid disorders do not affect in utero growth or delivery of the fetus and may be asymptomatic in the early stages. Phenylketonuria, tyrosinemia, and Hartnup disease are three clinically important early childhood amino acid disorders that are typically due to biochemical defects.
Etiology
With few exceptions, amino acid metabolic disorders are caused by autosomal recessive inheritance and are more common in the offspring of consanguineous marriages.
Symptoms
Currently, there are more than 100 hereditary diseases caused by disorders of amino acid metabolism. New discoveries will continue to be made as biochemical testing technology advances. The main clinical features are normal appearance and activity at birth, gradually appearing after half a year or one year of age with diminished intelligence, appropriate amino acid supplementation, dietary control of vitamins and other comprehensive treatment, many cases of neurological symptoms can be improved.
1.Hereditary tyrosinemia
(1) There are 3 types of hereditary tyrosinemia. The performance of each type is different. About half of the children have mild to moderate intellectual decline, may have self-injurious behavior and limb motor incoordination, language defects are more prominent. Type II At 1 year of age or almost 1 year of age, due to corneal erosion, it often causes tearing, photophobia and redness of the eyes, neovascularization and corneal clouding, keratosis palmaris and plantaris, often accompanied by hyperhidrosis and pain, which is an inflammatory reaction caused by crystalline tyrosine deposition, and nodularity is also the cause of keratoconus.
(2) Type I may have liver and spleen enlargement or cirrhosis, ascites and other manifestations of hepatic failure, and often dies after one or several years of illness. Tyrosinemia in the neonatal period can lead to liver failure and premature death. Increased blood and urine tyrosine levels are diagnostic, and blood methionine (methionine) and other amino acids may also be increased.
2. Hartnup’s disease
(1) Children are born normal, but symptoms appear in late infancy or early childhood. The characteristic clinical manifestation is the intermittent appearance of a red scaly rash over the face, neck, hands and feet, which resembles pellagra lesions.
(2) Growth retardation, episodic personality disorders such as emotional variability, inability to control temper, psychosis, hallucinatory psychosis, episodic cerebellar ataxia (unsteady gait, intentional tremor, and dysarthria, etc.), and occasional signs such as myoclonic spasms, vertigo, nystagmus, diplopia, and corneal eruption and ptosis may occur.
(3) Sun exposure, emotions, stress, and sulfonamides may trigger the onset of symptoms, which lasts about 2 weeks and is followed by a period of episodes of varying duration. As the child matures, the frequency of episodes gradually decreases, and some children may have mild persistent mental deterioration.
Examination
1. Laboratory tests
Blood, urine and stool routine, liver function, blood and urine amino acid content measurement are of diagnostic significance.
(1) Children with hereditary tyrosinemia have elevated blood tyrosine levels, elevated urinary tyrosine, and elevated blood methionine (methionine) and other amino acids.
(2) Children with Hartnup’s disease have increased urinary neutral amino acids, and normal levels of urinary proline, hydroxyproline and arginine.
2. Auxiliary examination
(1) Electroencephalography.
(2) Genetic testing and prenatal diagnosis.
(3) X-ray, CT and MRI examination.
3. Relevant examinations
Urinary amino acid nitrogen, total hydroxyproline, amino acid, arginine, proline, tyrosine.
Diagnosis
Diagnosis of liver failure is mainly based on the typical clinical manifestations of different types of amino acid metabolism diseases and laboratory tests, and genetic testing has the significance of confirming and differentiating the diagnosis.
Differential diagnosis
It should be differentiated from other causes such as lipid deposition disease, perinatal disease, neurological injury, mental retardation, epileptic seizures, tremor ataxia, tendon hyperreflexia, and hepatic dermatitis.
Treatment
1. Aminoaciduria without obvious clinical symptoms does not require special treatment.
2. Only symptomatic treatment can not change the prognosis and amino acid metabolism abnormalities, such as amino acid metabolism abnormalities in children with convulsive seizures must be treated with antiepileptic drugs, but can not improve the amino acid metabolism abnormalities.
3. Amino acid metabolism abnormalities that can be controlled by trial diet therapy, low protein diet, supplementation of semi-synthetic amino acid mixed milk that does not contain metabolic accumulator amino acids, maple syrup urine disease, urea metabolism disorder of hyperammonemia; restriction of amino acid intake, such as hyperlysinemia.
4. High-dose vitamin therapy can improve the symptoms of amino acid metabolism disease, this group of patients is caused by certain coenzyme deficiency and metabolic abnormalities, vitamin supplementation can change the metabolic process, such as vitamin B6 dependence, high-dose vitamin B6 used in the treatment of infantile convulsions; high-dose vitamin B1 used in maple syrup urine disease, vitamin B12 used in homocystinosis and so on. Supplementation of minerals and trace elements.
5. Hereditary tyrosinemia is mainly treated symptomatically. Low tyrosine and low phenylalanine diets can normalize growth and development and rapidly improve symptoms, but treatment must start early.
6. Levocanidin should be used for all diseases causing elevated coenzyme A esters in the mitochondria (care should be taken to identify long-chain fatty acid oxidation disorders).
Prognosis
The prognosis for different types of amino acid metabolism disorders varies, with most having a poor prognosis. Epileptic seizures and ataxia are both commonly due to biochemical abnormalities. Most children present with reduced learning ability and varying degrees of mental decline.
Prevention
Genetic disorders are difficult to treat with unsatisfactory results, making prevention all the more important. Preventive measures include avoiding consanguineous marriages, promoting genetic counseling, carrier gene testing and prenatal diagnosis, and selective abortion to prevent the birth of affected children.