The provision of dietary treatment is a powerful strategy for preventive management that is available for selected inborn errors of metabolism.Newborn screening programs allow recognition of certain of these disorders (e.g., phenylketonuria, galactosemia), while clinical acumen must be utilized for others (e.g., glycogen storage diseases).
An algorithm for approaching patients with suspected inborn errors of metabolism is presented in Chapter 1. The approach emphasizes the differences between abnormalities in “small” molecule metabolism (acute presentations with seizures, coma, hypoglycemia, acidosis, hyperammonemia, sepsis, or organ failure) and abnormalities in “large” metabolism (facial changes, visceromegaly, or neurodegeneration). While there is overlap between these simplified categories, the “small” molecule disorders are often diagnosed by amino acid and organic acid screening, while the “large” molecule disorders are recognized by neurologic, ophthalmologic, and tissue biopsy studies. In this chapter, the “small” molecule diseases are represented by galactosemia and phenylketonuria,while the “large” molecule diseases are represented by the glycogen storage diseases.
The definitive diagnosis for any inborn error of metabolism is to characterize a primary defect in the responsible gene (by DNA diagnosis) or its protein product (by enzyme assay). Often the demonstration of abnormal metabolites in plasma, urine, or affected tissues allows categorization of the disease and guides selection of the gene or enzyme to be tested. Participation of a metabolic disease specialist in the initial diagnostic evaluation is strongly recommended for interpretation of complex laboratory results (e.g., urine organic acid profiles).