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Diagnosis of inborn errors of metabolism
The following algorithms are available in Special Instructions:
-Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitines (also applies to any plasma C8, C6, and C10 acylcarnitine elevations)
-Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations (also applies to any plasma C4 acylcarnitine elevation)
-Newborn Screening Follow-up for Isolated C5 Acylcarnitine Elevations (also applies to any plasma C5 acylcarnitine elevation)
Organic acids occur as physiologic intermediates in a variety of metabolic pathways. 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.
The incidence of individual inborn errors of organic acid metabolism varies from 1 in 10,000 to >1 in 1,000,000 live births. Collectively, their incidence approximates 1 in 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 may 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 in 1,000 live births.
Organic acidurias typically present with either an acute life-threatening illness in early infancy or unexplained developmental delay with intercurrent episodes of metabolic decompensations in later childhood. A situation of severe and persistent metabolic acidosis of unexplained origin, elevated anion gap, and severe neurologic manifestations, such as seizures, 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 decompensations.
An interpretive report will be provided.
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, and recommendations for additional biochemical testing, and in vitro confirmatory studies (enzyme assay, molecular analysis).
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 and acylglycine analysis can effectively overcome the limitations of standard organic acid analysis for the investigation of non-acutely ill patients.
1. Lehotay DC, Clarke JT: Organic acidurias and related abnormalities. Crit Rev Clin Lab Sci 1995;32:377-429
2. Seashore MR: The Organic Acidemias: An Overview. Reviewed April 8, 2015. Available at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=oa-overview