Phenylketonuria clinical presentation

A 1-year-old girl presents at your clinic the day after you saw the 3-month-old boy. The symptoms are the same so you order a test on phenylalanine hydroxylase to confirm your diagnosis of phenylketonuria. To your surprise the phenylalanine hydroxylase activity is well within the normal range. Which of the following might you check next to support your diagnosis ... 

These three schemes of metabolism offer a unique perspective for discussing the analysis of metabolites in clinical chemistry labs. Traditionally, many laboratories have utilized the one analyte, one disease approach to testing. Hence, metabolite A in each of the scenarios would be a single measurement made in a laboratory, often by a relatively nonspecific test such as an immunoassay or fluorometric analysis. There are often numerous circumstances that can produce an elevation of a particular metabolite in addition to an enzyme deficiency produced by a metabolic disease. The result is a false positive. Measurement of more than one metabolite that is affected by a particular enzyme, Phe and Tyr as in the case of phenylketonuria (PKU), reduces the likelihood of a false positive as these amino acids are linked met-abolically. The case is similar in scenarios 2 and 3 where the pattern of metabolites may indicate one or more disorders that share common metabolic pathways. One final point regards scenario 2. Measurements of metabolites 2 or more steps away from the primary metabolic block, theoretically and in practice, are somewhat less reliable indicators of disease than the primary substrate. Often, however, no alternative is presented due to the primary substrate being chemically unstable or difficult to measure analytically. Generally, these metabolites are easier to detect in older infants as they accumulate over time. 

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