What Is Hyperammonemia?

Hyperammonemia is a clinical syndrome characterized by abnormally elevated blood ammonia levels and central nervous system dysfunction. Due to the low incidence of the disease and the lack of specific clinical manifestations, it is easy to cause misdiagnosis and missed diagnosis. Some patients cannot reach a correct diagnosis until clinical death.

Basic Information

English name: hyperammonemia
Visiting department: Endocrinology

Common locations: blood
Common causes: Insufficient biotin in the body, decreased enzyme activity, ammonia can not be smoothly metabolized

Causes of hyperammonemia

The protein that the human consumes every day is digested and broken down in the intestine to produce a certain amount of ammonia. Ammonia is a toxic substance, which is synthesized by urea urease to detoxify. The urea synthase required in this process contains biotin components, such as insufficient biotin in the body, decreased enzyme activity, ammonia cannot be smoothly metabolized, and can cause hyperammonemia.

Clinical manifestations of hyperammonemia

Mainly manifested by the neurotoxicity of hyperammonemia, the severity of clinical symptoms of hereditary hyperammonemia is parallel to the degree of enzyme activity deficiency, that is, the more severe the enzyme deficiency, the earlier the onset, the more severe the symptoms. In the neonatal period, symptoms and signs are closely related to brain dysfunction. Usually infants are normal at birth, and a few days later, symptoms occur after feeding a protein-containing diet, such as milk, which are manifested as antifeeding, vomiting, shortness of breath, lethargy, and fast. Into a deep coma, often with seizures. Physical examination revealed that in addition to deep coma, there may be large liver, increased or decreased muscle tone. Symptoms of childhood onset are relatively mild, with intermittent episodes. Acute hyperammonemia manifests as vomiting, neuropsychiatric symptoms such as ataxia, confusion, anxiety, irritability, and aggressive behavior, and can cause drowsiness and even coma. It can also manifest as anorexia and headache. Chronic hyperammonemia is mainly manifested by the symptoms of progressive cerebral degeneration, which may include physical dysplasia and mental retardation.

Hyperammonemia test

Increased blood ammonia

Blood ammonia is usually 234.8 to 587 mol / L (400 to 1000 g / dl), and the normal value reference range is 27 to 82 mol / L (46 to 139 g / dl). In the case of hyperammonia coma, blood ammonia can be as high as 352.2 1526.2 mol / L (600 2600 g / dl).

2. Quantitative amino acid analysis

Check blood and urine amino acids to determine if there is a specific increase. Particular attention should be paid to the quantitative analysis of glutamate, glutamine, alanine, citrulline, arginine, and arginylsuccinate urine to distinguish enzyme defects in the urea cycle.

3. Protein load test

When the urea cycle is impaired, the protein food is intolerant, and a protein load test can be performed for clinical diagnosis and detection of heterozygotes. Eat breakfast naturally, give protein, and observe changes in blood ammonia and blood, urine amino acids and orotic acid, measured once every 2 hours for a total of 3 times.

4. Blood glucose, blood gas analysis, organic acid in urine

Respiratory alkalosis is often present in urea cycle disorders. Organic aciduria is often accompanied by hyperammonemia, but it is different from urea cycle disease because of its lower blood sugar, metabolic acidosis, and excretion of specific organic acids in the urine.

5. Determination of enzyme activity

Hyperammonemia caused by lack of carbamoyl phosphate synthase (CPS) activity requires a percutaneous liver biopsy to determine CPS activity. The diagnosis of ornithine carbamoyl transferase (OTC) deficiency also requires the measurement of OTC activity in liver cells. The diagnosis of citrullineemia should be tested for the lack of argininosuccinate synthase (AS) activity. In the case of argininosuccinic aciduria, the activity of argininosuccinate lyase (AL) in liver cells, peripheral red blood cells, and skin fibroblasts can be measured. When arginineemia is suspected, liver, red blood cell, and white blood cell arginase activity should be measured.

6. Genetic analysis

DNA genetic diagnosis can be used for OTC deficiency and CPS deficiency.

7. Heterozygote detection

Can be based on pedigree analysis, protein load test, genetic analysis or enzyme activity check.

8. Imaging examination

Electroencephalogram examination has abnormal brain waves, brain CT examination is performed when conditions are available, and other routine examinations include ultrasound and X-ray examinations.

Diagnosis of hyperammonemia

Diagnosis is based on medical history, clinical manifestations, and examinations.

Differential diagnosis of hyperammonemia

Hyperammonemia needs to be distinguished from the following symptoms.

1. Neonatal transient hyperammonemia

Mainly seen in preterm infants. People with very high ammonia levels have severe neurological depression and have difficulty breathing. If early hemodialysis can relieve symptoms within 5 days, the prognosis is better. Asymptomatic hyperammonemia is also seen in low birth weight infants.

2. Organic aciduria

Often accompanied by hyperammonemia. It is characterized by normal blood amino acid quantification, low orotic acid in urine, increased specific organic acids in urine, low blood sugar, increased blood glycine, and metabolic acidosis.

3. Lysine urine protein intolerance

With hyperammonemia. Due to the defective transport of arginine, lysine, and ornithine by the renal tubules and intestinal epithelium, the above amino acids in the blood are increased, affecting the metabolic function of the urea cycle.

4. Hyperammonemia-Hyperornithinemia-Homocitrullineuria

HHH syndrome is a disorder in the transport of ornithine to the mitochondria.

Hyperammonemia treatment

1. Ammonia excretion provides amino acids

Blood ammonia should be expelled from the body as soon as possible, while sufficient heat and essential amino acids should be given to reduce the breakdown of protein in the body.

2. Strengthen renal excretion of ammonia

Give a sufficient amount of liquid and electrolyte, glucose and insulin can be added to supplement the calories, and 1 g / kg of fat is injected intravenously every day.

3. Intravenous sodium benzoate and sodium phenylacetate

Sodium benzoate can combine with endogenous glycine to form hippuric acid. The latter has a high renal clearance rate. Sodium phenylacetate combines with glutamic acid to form glutamic acid phenylacetate and is easily excreted from the urine. In the first aid, glucose can be added to sodium benzoate and sodium phenylacetate, which can be administered intravenously within 2 hours, and sodium benzoate and sodium phenylacetate can be given daily thereafter.

4.Arginine hydrochloride

Except for hyperammonemia caused by arginase deficiency, other cases can be treated with arginine. Arginine can both promote the excretion of ammonia and supplement essential amino acids in the body. In the case of neonatal hyperammonemia for the first time and the etiology is unknown, arginine can be given in first aid. Secondary to organic acidemia, hyperammonemia, arginine has no therapeutic effect. Benzoic acid, phenylacetic acid, and arginine can be used simultaneously for the best curative effect. After the first application, the patient should be kept on a quiet spot until the acute critical condition improves.

5. Hemodialysis or peritoneal dialysis

After a few hours of peritoneal dialysis, blood ammonia levels can be significantly reduced, and most of them can return to normal after 48 hours of dialysis.

6. Neomycin and lactulose

In order to reduce the intestinal bacteria's ammonia production, neomycin or lactulose should be given by nasal feeding or enema as soon as possible. The child's neurologically severe symptoms can be relieved through first aid measures, but it may take several days to be fully conscious.

7. Diet therapy

Limit protein intake and supply 1 to 2 g / kg of protein daily.

8. Supplement Carnitine

Carnitine should be added in the above treatment, because benzoic acid and phenylacetic acid can cause carnitine deficiency in the body.

9. Convulsion disables valproic acid

Because the drug can induce hyperammonemia.