Test ID: OAU
Organic Acids Screen, Urine

Diagnosis of inborn errors of metabolism

Organic acids are water-soluble compounds containing 1 or more carboxyl groups as well as other functional groups (-keto, -hydroxy). They occur as physiologic intermediates in a variety of metabolic pathways. The organic acidurias are a group of disorders in which one or more of these pathways are blocked, resulting in a deficiency of normal products and an abnormal accumulation of intermediate metabolites (organic acids) in the body. These excess metabolites are excreted in the urine and can be analyzed by capillary gas chromatography-mass spectrometry (GC-MS).

The incidence of individual inborn errors of organic acid metabolism varies from 1:10,000 to >1:1,000,000 live births. Collectively, their incidence approximates 1:3,000 live births. This estimate, however, does not include other inborn errors of metabolism (ie, amino acid disorders, urea cycle disorders, congenital lactic acidemias) for which diagnosis and monitoring also require organic acid analysis. All possible disease entities included, the incidence of conditions where informative organic acid profiles could be detected in urine is likely to approach 1:1,000 live births.

Organic acidurias share a common natural history, which is the occurrence of either acute life-threatening illness in early infancy or unexplained developmental delay with intercurrent episodes of metabolic decompensation in later childhood.

A situation of severe and persistent metabolic acidosis of unexplained origin, elevated anion gap, and severe neurologic manifestations should be considered strong diagnostic indicators of one of these diseases. The presence of ketonuria, occasionally massive, provides an important clue toward the recognition of disorders, especially in the neonatal period. Hyperammonemia, hypoglycemia, and lactic acidemia are frequent findings, especially during acute episodes of metabolic decompensation. These abnormalities warrant immediate verification by urine organic acid analysis using GC-MS.

An interpretive report will be provided.

An abnormal organic acid analysis is not sufficient to conclusively establish a diagnosis of a particular disorder. It is strongly recommended to seek confirmation by an independent method, typically by in vitro enzyme assay (blood or cultured cells, tissue biopsy) or molecular analysis. Rather than on individual abnormal values, interpretation is based on pattern recognition and correlation of positive and negative findings (for example, ketotic versus nonketotic dicarboxylic aciduria).

When no significant abnormalities are detected, the organic acid analysis is reported and interpreted in qualitative terms only. When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing, and in vitro confirmatory studies (enzyme assay, molecular analysis), name and phone number of key contacts who may provide these studies at Mayo Medical Laboratories or elsewhere, and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

The diagnostic specificity of organic acid analysis under acute and asymptomatic conditions may vary considerably.

Informative profiles may not always be detected in disorders where the excretion of diagnostic metabolites is a reflection of the residual activity of the defective enzyme, the dietary load of precursors, and the anabolic/catabolic status of a patient.

In some cases, methods of higher specificity and sensitivity such as acylcarnitine determination by tandem mass spectrometry and acylglycine determination by gas chromatography-mass spectrometry stable isotope dilution analysis can effectively overcome the limitations of standard organic acid analysis for the investigation of non-acutely ill patients.

1. Goodman SI, Markey SP: Diagnosis of organic acidemias by gas chromatography-mass spectrometry. New York, Alan R Liss, 1981

2. Sweetman L: Organic acid analysis. In Techniques in Diagnostic Human Biochemical Genetics. Edited by FA Hommes. Wiley-Liss, New York, 1991, pp 143-176

3. Lehotay DC, Clarke JT: Organic acidurias and related abnormalities. Crit Rev Clin Lab Sci 1995;32:377-429

4. Seashore MR: The Organic Acidemias: An Overview. Available from http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=oa-overview Reviewed December 22, 2009