Detection of Human Inborn Errors of Metabolism by Examination of Urinary Metabolites

An increasing number of recessively inherited human diseases are being explained in terms of a missing or defective enzyme. The resulting aberration of metabolism is reflected, in many cases, in an altered composition of metabolites in the urine and other body fluids. Progress in this field is dependent on making the initial association between a familial disease and an aberration of body chemistry. The development of comprehensive analytic systems for the detection of abnormal quantities or kinds of metabolites in biologic fluids obtained from patients with inherited diseases should greatly facilitate this process. Biochemical characterization, at an enzyme level, then becomes possible and is essential for improved diagnosisand rational approaches to treatment of the disease. IN RECENT YEARS, remarkable progress has been made in our under-standing of the genetic mechanisms involved jim production of human disease states. An ever-increasing number of recessively inherited dis-eases are being explained in terms of a deficient or defective eimzyme resulting from a defective pair of genes. The resulting disruption in a normal pathway of metabolism is often reflected in a change in com-position of urinary metabolites. As a consequence of these advances, the clinical recognition and the biochemical characterization of many of these familial diseases have become more precise, and some types of disorders can now be treated successfully. This progress has been greatly facilitated by the remarkable advances in our knowledge of basic biochemistry made in the past two decades, as well as the in-creasing sophistication of the clinicians in the field of biochemistry. However, the rate of this progress in explaining hereditary diseases in terms of biochemical defects is seriously hampered by limitations that are, to a large extent, technical problems. One of the most difficult problems that repeatedly confronts th