Inborn errors of metabolism in the newborn: clinical presentation and investigation

Inborn errors of metabolism are genetically determined interruptions of one (or several related) metabolic pathway(s). Clinical symptoms are caused by deficiency of the pathway product and/or toxicity resulting from the accumulation of an intermediary compound. Inborn errors of metabolism are mostly recessive disorders, with clinical symptoms rare in heterozygous individuals. The genetic defects involve homozygous (autosomal) or hemizygous (X-linked) mutations in genes encoding proteins with a single enzymatic function. However, interruptions in biochemical pathways may also result from mutations affecting the bioavailability of an enzymatic co-factor or disordered transport of the enzyme across intracellular membranes. In the latter two circumstances it is likely that more than one enzymatic process will be affected.

The five main modes of presentation of IEM in the neonatal period are acute intoxication, energy deficiency, organomegaly, profound central hypotonia, and malformations. The common diagnoses in each of these groups will be presented, with brief descriptions of the currently available options for diagnosis and therapy.