Hyperammonemia – Causes, Symptoms, Diagnosis and Treatment

What Is Hyperammonemia?

It is a metabolic disorder which results from a high level of ammonia in the bloodstream. It is a serious condition that may give rise to acute problems, such as Encephalopathy and death.

Hyperammonemia ICD 9 Code

The ICD 9 Code for Hyperammonemia is 270.6.

Hyperammonemia Meaning

In healthy individuals, ammonia levels in the bloodstream stay between 10 and 40 µmol/L. as compared with a BUN level of 6-20 mg/dL. In a healthy adult, the total soluble ammonia level is only 150 mcg with 5 L of circulating blood. This is in contrast to the presence of about 1000 mg of urea and nitrogen.

Hyperammonemia Types

The condition is usually differentiated into two types. These are:

Primary Hyperammonemia

It arises due to various inborn metabolic errors that are marked by decreased activity of any of the enzymes involved in the urea cycle of an individual.

Secondary Hyperammonemia

It results from inborn intermediary metabolic defects marked by lowered activity in enzymes which are not involved in the urea cycle such as Propionic academia and Methylmalonic acidemia. It is also caused by the dysfunction of cells that contribute in a major way to metabolism. Hepatic Failure is one such cause.

Hyperammonemia Signs and Symptoms

The specific physical symptoms of Hyperammonemia are very few in number. Certain medical researchers have, however, identified some discomforting symptoms like:

  • Dehydration
  • Lethargy
  • Rapid respiration
  • Decreased muscular strength

Patients of this syndrome are also found to develop fontanelles that are larger than normal. Fontanelles are soft spots on the skull surface of babies where the bone has not had a complete formation as yet.

What Causes Hyperammonemia?

This condition is typically caused by two factors. It may be a result of processes that raise production of ammonia. Hyperammonemia, resulting from decreased ammonia elimination, can occur due to medicinal side effects as well as the onset of conditions like:

  • Fulminant hepatic failure
  • Portosystemic shunting
  • IEM

Hyperammonemia may also arise due to processes that reduce elimination of ammonia. Some conditions increasing ammonia production are:

Protein metabolism

It enhances ammonia levels in the bloodstream and may be accompanied by GI hemorrhage, trauma, total parenteral nutrition (TPN), and steroid use.


Some drugs disrupt the urea cycle and give rise to Hyperammonemia. These include Glycine, a medicine that is used at the time of transurethral resection of the prostate. Glycine stimulates production of ammonia in humans.

Physiologic stressors

Certain physiologic stressors cause stress and arouse Hyperammonemia in sufferers of metabolic disorders. These agents include dietary changes, fever, Pneumonia, Pregnancy, infection with urease-splitting organisms, GI bleeding and upper respiratory tract illnesses.

Idiopathic hyperammonemia (IHA)

Idiopathic hyperammonemia (IHA) is a medical condition in which increased levels of ammonia are disproportional to liver dysfunction without the presence of an inherited metabolic disorder.

Other conditions that may elevate ammonia production involve herpes infection, multiple myeloma, urinary diversion or infection with organisms that split urease enzyme.

A person is unlikely to suffer from this condition unless there is some type of defect in the metabolic conversion system. In newborns, the defect often results from genetic defects. In older adults, however, the defect mostly occurs due to a diseased liver. However, onset of genetic disorders of the urea cycle in a growing number of adults is also being seen as a reason.

Hyperammonemia and Liver Failure

In adults, Acute Hyperammonemia is most commonly caused due to Fulminant hepatic failure. Every year, approximately 2,000 cases of this condition are found to result from liver failure. Liver failure can result from diverse factors such as,

  • Acetaminophen toxicity
  • Drug reactions
  • Viral hepatitis (A or B)
  • Idiopathic causes
  • Viral infections
  • Autoimmune diseases
  • Vascular diseases
  • Pregnancy-related conditions (such as Eclampsia)
  • Toxins (such as herbs and mushrooms)

The liver is an important organ that is mainly responsible for the degradation of ammonia. Liver dysfunction leads to improper metabolizing and elimination of ammonia. This results in reduced ammonia removal from the human body.

Hyperammonemia Diagnosis

The diagnosis of Hyperammonemia involves identifying the cause of the condition. Medical examination should include:

  • Liver function tests
  • Coagulation tests
  • Measurement of acetaminophen levels
  • Viral serologies

In case of a suspected IEM, patients should undergo medical tests that evaluate the levels of organic acid, amino acids and orotic acid in the urine. A liver biopsy may be considered for confirmation of the diagnosis of the disease. Quantitative plasma and Carnitine evaluation should also be done.

If an acute liver failure is suspected due to drug usage, the social history should be considered and a careful medical treatment has to be carried out. Abdominal CT scanning may help in an accurate diagnosis.

Hyperammonemia Differential Diagnosis

The differential diagnosis of Hyperammonemia should aim at distinguishing the condition from other similar disorders, such as

  • Portal vein thrombosis
  • Fatty infiltration
  • IEM

Primary cases of the condition should be differentiated from Urea Cycle Defects and Transient Hyperammonemia of the Newborn. Secondary cases should be distinguished from Organic Acidopathies, Fatty Acid Oxidation Defects and Reye’s Syndrome.

Hyperammonemia Treatment

The treatment of Hyperammonemia aims at restricting the intake of ammonia as well as increasing its excretion. Physicians make this possible by prescribing pharmacologic agents like Sodium benzoate and Intravenous Sodium Phenylacetate. These are commonly used as adjunctive therapy for curing the condition in patients suffering from deficiency of Urea Cycle Enzyme.

Hyperammonemia Prognosis

If left untreated, this condition may give rise to an acute brain disorder known as Encephalopathy. The condition involves 100% mortality in the absence of cure. However, the prognosis can be good if the problem is treated properly and in time.

Hyperammonemia Management

People suffering from chronic disorders are at a life-long risk of suffering from Hyperammonemia episodes. For such patients, management involves long-time follow up and monitoring of the ammonia levels. A multidisciplinary approach, involving Genetic, Dietary, Metabolic, Pediatric and Neurological factors, needs to be followed for this disease. Specific supportive plans need to be used for dealing with acute episodes. Therapies used for this disorder need to focus on controlling the symptoms and avoiding its acute episodes.






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