Difficulties and pitfalls in the interpretation of screening tests for the detection of inborn errors of metabolism

Abstract

A review of factors which may be responsible for false positive and false negative results in a screening program for the detection of inborn errors of metabolism is presented. Administration of medication, dietary therapy, chemical treatment of specimens, delay in analysis, hypersensitivity of procedures utilized, interfering metabolites and inadequate metabolic development or enzymatic maturation in the patient may all produce results resembling an actual inborn error of metabolism. Inadequate nutritional intake prior to procurement of specimen and loss of material during analytical procedures may produce false negative results. As well, certain less severe variants of inborn errors may present in an unusual manner or may only present during periods of stress to the patient. These factors are discussed in relation to the performance of a metabolic screening program. It is suggested that these progrms should be performed by specialized, central laboratories experienced in the complexities of detection of inborn errors of metabolism.