Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication. Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least >1:2000 newborns) and represents an important challenge for all public health systems. Types and clinical presentation of protein-dependent inborn errors of metabolism—this chapter discusses amino acid disorders, organic acid disorders, and urea cycle defects. The disease spectrum is broad, but follows a distinct pattern in specific disorders. Investigation and management—every infant presenting with symptoms of unexplained metabolic crisis, intoxication, or encephalopathy requires urgent evaluation of metabolic parameters, including analyses of arterial blood gases, serum glucose and lactate, plasma ammonia and amino acids, acylcarnitine profiling in dried blood spots, and organic acid analysis in urine. This chapter discusses the basic principles of acute emergency therapy and of long-term treatment, which aims principally to mitigate the metabolic consequences of enzyme deficiencies by compensating for them. Successful treatment of affected individuals is often difficult to achieve. Careful supervision in metabolic centres involving an experienced multidisciplinary team is invaluable for the best outcome.
Fast and accurate quantitative organic acid analysis with LC-QTOF/MS facilitates screening of patients for inborn errors of metabolism
