Inborn Errors of Metabolism

Inborn errors of metabolism are disorders of great importance to physicians treating newborns because rapid diagnosis and appropriate treatment of these conditions are directly related to the patient’s outcome in terms of mortality and morbidity. Although individually rare, as a group these diseases are relatively frequent and collectively their incidence may approach 1 in 800 to 2500 births [1, 2]. The presentation of these disorders may occur in any age group, from fetuses and newborns to adulthood. Neonatal onset is common because the newborn period is a time of substantial catabolism. The main problems facing the physician caring for the sick newborn are when to consider an inborn error of metabolism, what test to order to determine quickly and efficiently whether the patient has an inborn error of metabolism, and what therapy to initiate given a specific or a suspected diagnosis. Unfortunately, given the limited repertoire of symptoms of the newborn, the early presentation is generally non-specific and usually includes poor feeding, breathing difficulties, lethargy, hypotonia, vomiting, hypothermia, and seizures. Therefore, patients with acute metabolic presentation are often misdiagnosed with other more common conditions such as sepsis, pulmonary disease, pyloric stenosis, and Reye syndrome. However, clues from the history, from the clinical presentation or from basic biochemical studies should raise the suspicion of a metabolic disease (Tables 120.1–120.7). A wide range of tests are required for the diagnosis of inborn errors of metabolism and the level of clinical and biochemical experience required is often substantial. Nevertheless, the neonatologist can initiate appropriate investigation with a relatively small number of laboratory tests which are readily available in most hospitals (Table 120.8). In many circumstances, the prevention of death or permanent neurologic sequelae is dependent on early diagnosis and institution of appropriate treatments. In addition, an accurate diagnosis is of primary importance for parental counselling.