Clinical and biochemical approach to the neonate with a suspected inborn error of amino acid and organic acid metabolism

Disorders of amino acid and organic acid metabolism collectively represent a group of over 70 inherited diseases that are most frequently encountered in the neonatal period. A neonate with clinical symptoms caused by one of these disorders is a real clinical emergency, a situation complicated by the similarities to the manifestations seen in sepsis or asphyxia. Delay of diagnosis and proper treatment often results in severe morbidity and high mortality. The vast majority of these patients are likely to be transferred to a neonatal intensive care unit, suggesting that amino acid and organic acid biochemical screenings should be performed in these newborns routinely at admission. The analysis of amino acids and acylcarnitines in blood spots by tandem mass spectrometry has the potential to significantly improve the morbidity and mortality rates of metabolic disorders with neonatal presentation. In the case of disorders lacking an effective treatment, an early diagnosis could lead to proper genetic counseling of the parents and to the option of reliable prenatal diagnosis of future pregnancies. This review offers an updated summary of the clinical, biochemical, and therapeutic features of the aminoacidopathies and organic acidurias most likely to be encountered in neonatal clinical practice.