What is the laboratory test for hyperammonemia?

From the Guidelines

Hyperammonemia is diagnosed through a laboratory test that measures blood ammonia levels, typically using an enzymatic kinetic assay that reacts with α-ketoglutarate and NADPH to form glutamate and NADP+ 1.

Key Considerations for Laboratory Testing

• The measurement of ammonia is extremely sensitive and requires careful control of pre-analytical events such as delayed sample processing, temperature, and hemolysis 1.
• Blood samples should be collected in an EDTA-containing tube, placed on ice, and transported to the laboratory at +4°C within 60-90 minutes 1.
• The delay between sampling and analysis should be kept within 2 hours, and heparin, EDTA, and oxalate anticoagulated plasma have been tested with EDTA-anticoagulated matrix found to be superior 1.

Interpretation of Results

• Hyperammonemia is defined as >100 µmol/l (170 µg/dl) in neonates or ≥50 µmol/l (85 µg/dl) in term infants, children, and adolescents 1.
• Typically, blood ammonia concentrations ≤35 µmol/l (<60 µg/dl) are considered normal, whereas high concentrations can produce toxic effects and levels >200 µmol/l (341 µg/dl) are associated with poor neurological outcomes 1.

Clinical Significance

• Early symptoms of hyperammonemia include lethargy, loss of appetite, and vomiting, which can progress to hyperventilation, hypotonia, ataxia, disorientation, seizures, and coma if left untreated 1.
• The clinical features of an acute hyperammonemic episode depend on the age of the patient and the cause of the elevation in plasma ammonia levels 1.

From the Research

Laboratory Test for Hyperammonemia

The laboratory test for hyperammonemia typically involves measuring the level of ammonia in the blood.

• Blood sampling is the most common method used to measure ammonia levels 2, 3.
• The measurement of ammonia in human breath has also been explored as a potential non-invasive means of measuring systemic ammonia 2.
• Plasma ammonia measurement can be influenced by pre-analytical conditions, which may lead to false positives 4.
• Delays in transportation to the laboratory after collection or before completion of analysis can also potentially contribute to hyperammonemia 5.

Factors Affecting Ammonia Measurement

Several factors can affect the accuracy of ammonia measurement, including:

• Pre-analytical factors such as sample handling and transportation time 5, 4.
• Analytical factors such as the quality of the sample draw and preparation for analysis 2.
• The use of capillary samples and delay between sampling and centrifugation can also contribute to false positives 4.

Interpretation of Results

The interpretation of ammonia measurement results requires careful consideration of potential pitfalls and factors that can affect accuracy.

• Hyperammonemia can be a potentially important indicator of impairment in intermediate metabolism, but lack of experience in sample handling and confusion about what level is significant can lead to its devaluation as a test 3.
• The clinical consequences of false positives can be limited, but additional blood sampling and laboratory testing may be necessary 4.