Inborn errors of metabolism are recognized with increasing frequency as a cause of disease manifestations in every organ and at every life interval from the fetus to the geriatric patient [1]. Yet their collective incidence is often underestimated, and diagnostic errors often occur, leading to devastating consequences for patients and their families [2]. Among an increasing number of single-gene disorders that are currently recognized, inborn errors of the intermediate metabolism of amino acids, carbohydrates, and fatty acids deserve special attention. The majority of these diseases have been identified within the past 30 years, primarily through the detection of endogenous metabolites abnormally accumulating in biologic fluids [3]. This chapter focuses predominantly on the laboratory diagnosis of three major groups of metabolic diseases: organic acidurias, congenital lactic acidemias, and disorders of fatty acid transport and oxidation. Aspects of urea cycle defects and amino acid disorders are covered to a lesser extent.

The inborn errors listed in Table 22.1 share a common natural history, which is the occurrence of either acute life-threatening illness in early infancy or unexplained developmental delay with intercurrent episodes of metabolic decompensation in later childhood. Unfortunately, the clinical presentations of these diseases are often attributed to a variety of other causes (Table 22.2). Indeed, once a patient is properly diagnosed with a metabolic condition, it is not uncommon to find retrospectively that a sibling within the same family presented with similar symptoms but had passed away without a precise diagnosis.