Clinical Chemistry, Vol 7, 441-456, Copyright © 1961 by the American Association for Clinical Chemistry

Problems in the Chemical Diagnosis of Some Hereditary Metabolic Diseases

¹ Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich.

Some hereditary or acquired, qualitative or quantitative differences in the urinary excretion patterns of certain phenolic acids, -keto acids, and indolic acids have been reviewed and discussed. The ketoacidurias are summarized in Table 1. As can be seen, there is considerable overlap in the excretion of primary, and presumably secondary metabolites. From these comparisons together with the other disorders discussed throughout this presentation, the following conclusions might be drawn:

1. Phenylketonuria can be readily separated from the other ketoacidurias by the presence of increased amounts of o-hydroxyphenylacetic acid.

2. The increased excretion of -ketoisocaproic acid and -ketoisovaleric acid should be definitive for branched-chain ketonuria.

3. Secondary disturbances in tyrosine and tryptophan metabolism, which are associated with many of these disorders, are often expressed in an increased production of the tyrosine metabolite p-hydroxyphenylpyruvic acid and its derivatives (which appear to be characteristic of liver dysfunction in both hereditary and acquired diseases) and in an increased excretion of the tryptophan metabolites of indoleacetic acid, indolelactic acid, and indican, and a decreased excretion of 5-hydroxyindoleacetic acid.

4. Because of the biochemical or symptomatic similarities between many metabolic disorders, it is sometimes difficult to make an accurate diagnosis unless variations in the excretion patterns for each disease entity are thoroughly understood, so that overlapping factors or variations in one factor will not confuse the diagnosis.

5. The dietary and drug intake of the patient under observation must be assiduously controlled before an abnormal, or abnormally increased, metabolite can be assigned an endogenous metabolic origin.

Keeping these facts and precautions in mind should reduce the likelihood of reporting a variant of a known hereditary metabolic disease as a new disorder. Nevertheless, since the study of metabolic diseases is so new, it is important at this stage to report all significant variations of even the well-established diseases.