Clinical evaluation and emergency management of inborn errors of metabolism presenting in the newborn.
Close to 500 biochemically diverse genetic metabolic disorders have been identified. Despite their diversity, these diseases share a number of features. First, the majority of patients with an inborn error present clinically with one of five general phenotypes; acute encephalopathy, progressive encephalopathy, primary muscle disease, primary liver disease or primary renal disease. Encephalopathy is by far the most common clinical manifestation of inborn errors of metabolism, and may be acute, intermittent, chronic (progressive), or even non-progressive. Although the five major phenotypes are a useful clinical guide, other clinical presentations of course occur, and some are virtually specific to a single disease or group of disorders. Second, almost all inborn errors are recessive in inheritance, and most of these conditions map to one of the 22 autosomes. Third, specific and effective treatment of inborn errors is often made possible by our understanding of their biochemical bases. Because inborn errors are genetic diseases, families with affected children can be made aware of the risk of recurrence, through genetic counselling. In many instances, presymptomatic treatment of affected relatives, carrier testing, and prenatal diagnosis can be offered. The types of inborn errors and their mode of presentation in the newborn are discussed, along with a schema permitting their rapid diagnosis. The principles of emergency and long term management are also discussed, with particular emphasis on those disorders that present in the newborn period with an acute encephalopathy, the so-called "small molecule" disorders.
Christodoulou
John
J
Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, NSW Australia.
D000208:Acute Disease; D000465:Algorithms; D020739:Brain Diseases, Metabolic, Inborn / Q000145:classification / Q000175:diagnosis* / Q000628:therapy*; D004638:Emergency Treatment / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015997:Neonatal Screening