The present invention relates generally to diagnostic medicine and more specifically to methods for diagnosing metabolic disorders.
Metabolism is the process of building the body's molecular structures from nutrients (anabolism) and breaking them down for energy (catabolism). Metabolic processes result in growth, produce energy, eliminate wastes, and control distribution of nutrients in the body. Homeostasis, or a steady state, in the body is a result of normal metabolism.
Enzymes play an important role in metabolism because they catalyze conversion of one molecule to another during metabolic processes. When a metabolic enzyme is faulty or present in an abnormal amount in an individual, a metabolic disorder can result. Metabolic disorders are frequently due to genetic inheritance that leads to absence or overproduction of an enzyme or production of a faulty enzyme.
As an example, deficiencies produced by an inactive gene can prevent the body from making an enzyme (or enzymes) needed to break down certain amino acids or types of fats. Such an enzyme deficiency typically prevents normal metabolism of a nutrient, causing the nutrient or its metabolite to build up in the body to toxic levels. An enzyme deficiency can also cause nutrient deficiencies when an enzyme is unable to make a normal end-product of a metabolic process. Nutrient deficiencies resulting from metabolic disorders can lead to impaired growth and development, and other severe health problems.
Many inherited metabolic disorders are fatal in the first weeks or months of postnatal life, for example, severe defects in the conversion of pyruvate to acetyl coenzyme A (CoA), some urea cycle defects, and severe defects in the processing of fructose. Infants and children with a treatable metabolic disorder are often identified by newborn screening in developed countries. For example, testing for phenylketonurea is routine practice in developed countries. Phenylketonurea is an example of a relatively common inherited metabolic disorder and it occurs in about one out of 16,000 live births in the United States. Individuals having phenylkentonuria do not produce the enzyme necessary to break down phenylalanine (an amino acid). Fortunately, when recognized, this metabolic disorder can be successfully treated by dietary restriction.
Unfortunately, newborns are not typically screened for other metabolic disorders such as homocysteinuria, maple syrup urine disease, organic acid disorders, and disorders of fatty acid oxidation. As a result, these disorders are often detected in infants and children after damage has occurred and effects such as developmental delay and mental retardation become apparent. However, such effects often can be reduced or avoided with early detection and sustained dietary restriction. Such early detection involves examining a blood sample for an enzyme activity or a metabolic marker (a metabolite).
Wide-spread newborn testing for multiple inherited metabolic disorders has been unavailable due, in part, to cost associated with each test. One approach for reducing costs is to examine multiple enzyme activities and metabolites and in a single test. However, development of multi-enzyme/metabolite testing has been hindered by the different conditions needed for enzyme tests in comparison to metabolite tests. Currently, enzyme and metabolite tests cannot be carried out simultaneously from a single patient sample.
Thus, there exists a need for methods for efficiently diagnosing a metabolic disorder in an individual. The present invention satisfies this need and provides related advantages as well.