Introduction
Amino acid carbamoyltransferase deficiency(Ornithine transcarboxylase deficiency, OTCD) is a rare rare congenital genetic metabolism, patients with interrupted urea cycle, increased blood ammonia, decreased blood citrulline, arginine, elevated glutamate, alanine, and urine Acid and pyrimidine excretion increases, and care is more special.
Overview
The absence of ornithine carbamoyltransferase deficiency (OTC) is the most common of urea cycle enzyme deficiency and is also X-linked. Hemizygous male children are seriously ill, most of them are in the neonatal period or in infants; children with heterozygotes are mostly mild or have no clinical symptoms due to different degrees of enzyme deficiency. Severe cases of children often vomiting, refusal to eat, lethargy, convulsions, low muscle tone, coma and other symptoms within a few days after birth, or even death; mild interstitial recurrent episodes, lethargy, irritability, restlessness, ataxia Etc. Eating high-protein foods, infections, trauma, surgery, etc. are all possible predisposing factors. Intelligent backwardness, microcephaly, and hepatomegaly are common. Laboratory tests are similar to the CPS deficiency type, but the urinary whey acid output is increased. Ornithine carbamoyltransferase deficiency (OTCD) is a rare congenital genetic metabolic disease, patients with interrupted urea cycle, increased blood ammonia, decreased blood citrulline, arginine, elevated glutamate, alanine And uric acid and pyrimidine excretion increased, eventually encephalopathy, etc.
Cause
Ornithine transcarbamylase (OTC) is the second enzyme in the urea cycle. Ornithine and carbamoyl phosphate form citrulline under the action of OTC, which is due to the lack of OTC. Congenital metabolic disease caused. As a result of the lack of OTC, the metabolism of carbamoyl phosphate is inhibited, and the amount of orotic acid in the urine is greatly increased, and uridine and uracil can also be detected in the urine.
Genetic form
X-chromosomal linkage inheritance.
Clinical features
Mainly for different symptoms such as low appetite, vomiting, disturbance of consciousness and paralysis. Male patients are usually diagnosed in the neonatal period or early in the baby. However, there are also reports of cases of childhood and adulthood. Because the disease is a x-linked genetic disease, the clinical symptoms of male patients are heavier and the prognosis is worse; the clinical symptoms of female children are different.
Pathogenesis
Hyperammonemia is the most important manifestation of various urea cycle enzyme deficiency diseases. A large amount of ammonia molecules produced by amino acid degradation rapidly form glutamine with glutamate in brain cells and accumulate in brain cells, resulting in increased osmotic pressure. It causes brain cell edema. Because astrocytes are rich in glutamine synthetase, edema is mainly astrocytes. Cerebral edema not only causes insufficient blood supply, but also impairs the function of neurons, axons, dendrites and synapses, leading to a series of brain metabolism and neurochemical abnormalities, resulting in a corresponding clinical symptom, a hyperammonemia encephalopathy. In addition to the defects of CPS and NAGs, all other types cause the accumulation of carbamyl phosphate. When it accumulates to a certain amount, it will diffuse into the cytoplasm and bind to aspartic acid to form orotic acid, which is involved in the pyrimidine synthesis pathway. Excreted from the urine.
Clinical manifestation
The clinical manifestations of various enzyme deficiency in the urea cycle are mainly neurological symptoms caused by hyperammonemia, but the variation of symptoms between different types or different types of children is greater, and the enzyme deficiency is more Near the beginning of the urea cycle, the more severe the symptoms. The age of onset of this group of diseases can range from the neonatal period to the adult stage. Most of the babies born in the neonatal period are full-term infants, and everything is normal at the time of delivery; there are no obvious symptoms within 24 to 72 hours after birth. Then gradually appear drowsiness, refusal to eat, the disease progresses rapidly, vomiting, body temperature rise, excessive ventilation, etc. can occur within a few hours, and sleep falls into a coma. At this time, if the serum urea nitrogen level is often lower than lmg/dl, the blood ammonia concentration is increased; CT brain scan can find cerebral edema, but most of the children are misdiagnosed as diseases such as lung disease, sepsis or intracranial hemorrhage, resulting in improper treatment. Born. Late-onset patients are seen at various ages, and infancy may be associated with feeding from breastfeeding to normal milk (containing higher protein); older children or adults may be caused by eating high protein. Mild disease can be improved after stopping taking human protein or intravenous infusion of glucose solution; severe cases are easily misdiagnosed as gastroenteritis, periodic vomiting, encephalitis, Reye syndrome, epilepsy, etc. in the occurrence of hyperammonemia. No jaundice hepatitis and other diseases. Patients with longer course and frequent episodes are often accompanied by growth retardation and seizures.
diagnosis
For patients with symptoms, the first thing is to measure the concentration of ammonia in the blood. Unless the tissue is hypoxic, liver and kidney function maintains normal function, but there are exceptions. The next step is to measure the concentration of amino acids in the blood. The values of ornithine, glutamine, and alanine increase, and the values of citrulline and arginine decrease. The amino acid concentration and organic acid concentration in the urine of the patient can also be used as reference values. In addition to high blood ammonia, the concentration of urinary orotic acid is clinically diagnosed. This test can also be used to detect asymptomatic carriers. If someone in the family has had this disease, amniotic fluid can be taken for DNA testing during pregnancy.
treatment
The goal of treatment is to correct biochemical disorders and ensure nutritional needs. Under high blood ammonia conditions, immediately limit the protein diet, strengthen the non-protein (carbohydrate and fat) heat source, and avoid decompensation. If severe high blood ammonia causes coma (some patients may have blood ammonia higher than 2000m g/dl), blood ammonia should be quickly removed by hemodialysis. Low protein diet
The amount of protein intake is determined by the age of the patient and the severity of the disease, and the needs of each patient are quite different. Six months ago, due to the period of rapid growth, patients may need 1.5g / kg / day or more protein; pre-school period, protein intake is usually reduced to 1.2 ~ 1.5g / kg / day; school-age children, can drop To 1g / kg / day. After puberty, the amount of protein can be less than 0.5g / kg / day.
drug
The drug provides another way to eliminate waste nitrogen.
1.sodium benzoate(Ucephan): combines with glycine to form hippurate, which is then excreted in the urine. 1 mol of nitrogen was removed per 1 mol of benzene. The usual dose is 250 mg/kg/day; the oral dose is 375 m g/kg/day, taken 3-4 times with a low protein diet. Side effects are nausea, vomiting, tinnitus, and visual impairment.
2. Sodium phenylbutyrate (Buphenyl): It is oxidized to phenylacetic acid in the liver and then combined with glutamine. The final product, phenylacetylglutamine, is excreted in the urine. 2 mol of nitrogen is removed per 1 mol of benzene. The dose given was 0.5 mg/kg/day.
3. Arginine: After the action of arginase, 1 mol of arginine is decomposed into 1 mol of urea and 1 mol of ornithine. In the case of high blood ammonia, a dose of 600 mg/kg/day is administered. Stable children are given an oral dose of 400-700 mg/kg/day. The prognosis of the patient is related to the age and the condition at the time of diagnosis. In patients with symptoms during the neonatal period, the prognosis is poor, and most patients have some obvious complications. It is necessary to cooperate with doctors and dietitians for a long time, continue outpatient follow-up, conduct regular biochemical tests, and record the development of height and weight to grasp the patient's condition. Some patients can consider liver transplantation in detail to provide a better prognosis.
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