Institute of Genomic Medicine
Organic Aciduria
BACKGROUND:
The analysis of organic acids by gas chromatography/mass spectrometry (GCMS) has become established as an important procedure for the diagnosis of inherited disorders of amino acid and organic acid metabolism. The test is used to determine the presence or absence of diagnostic organic acids in patient urine samples.
INCIDENCE:
Varies with the disease; most are rare, but not unheard of. There are no accurate prevalance figures because universal neonatal screening is not performed, many affected infants may die in early infancy and other cases go undiagnosed.
INDICATIONS FOR TESTING:
Symptoms of lethargy, coma, hypotonia, hypertonia, tachypnea, seizures, ataxia, vomiting, failure to thrive, developmental delay, hepatomegaly, and cytopenia can be due to abnormalities of organic acid metabolism. Abnormalities of clinical chemistries such as metabolic acidosis, low bicarbonate values, increased anion gap, hyperammonemia, hypoglycemia, lactic acidemia, triglyceridemia, elevated levels of free fatty acids, and ketosis may be suggestive of organic acid abnormalities.
PROCEDURE:
The important steps of the procedure for analysis are:
- isolation of the organic acid from urine by solvent extraction
- formation of volatile derivatives
- GCMS analysis
A creatinine level is also performed on the urine in order to control the creatinine equivalent injected on the column.
SAMPLE REQUIREMENTS:
At least 10cc of urine should be collected for analysis. First morning urines are standard, as they are usually concentrated and best reflect an individual's metabolism; 24 hr. urines will be accepted, although they are often more dilute.
INTERPRETATION:
The patient's chromatogram will be compared to normal profiles. Peaks are identified by comparison to standard acid profiles and combined gas chromatography/mass spectrometry. The interpretation of the levels of organic acids for diagnostic purposes depends on a pattern of abnormalities, since the elevation of a single compound may not be diagnostic. It must be emphasized that normal concentrations of organic acids in a single specimen, especially when the patient is clinically well, cannot rule out an organic aciduria. Specimens from periods of illness are more helpful and should be obtained. On the other hand, the modest elevation of an acid in a sick child may be nonspecific and does not necessarily indicate a specific disorder. Again, repeat samples should be analyzed to determine if it was a transient abnormality.
