Recent advances in the diagnosis and treatment of
inborn errors of metabolism have improved substantially the prognosis for many of these conditions. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. A practical clinical approach to the recognition of
inborn errors of metabolism in the young infant is presented in this review. Indications for specific laboratory studies are discussed. Guidelines are provided for the stabilization and
emergency treatment of
critically ill infants. This approach will identify those infants who will benefit from additional evaluation and specific treatment. Many of the
inborn errors of metabolism, including
urea cycle defects, organic acidemias, and certain disorders of
amino acid metabolism, present in the young infant with symptoms of an acute or chronic
metabolic encephalopathy. Typical symptoms include
lethargy, poor feeding,
apnea or
tachypnea, and recurrent
vomiting.
Metabolic acidosis and/or
hyperammonemia are observed in many of these conditions, but there are notable exceptions, including
nonketotic hyperglycinemia and
molybdenum co-factor deficiency. Therefore, appropriate laboratory testing for metabolic disorders should be performed in any infant who exhibits these findings. Although
sepsis may be the initial consideration in a neonate with these symptoms,
inborn errors of metabolism should always be in the differential diagnosis, particularly in a full-term infant with no specific risk factors.
Hypoglycemia may be the predominant finding in a number of
inborn errors of metabolism, including
glycogen storage disorders, defects in gluconeogenesis, and
fatty acid oxidation defects. The latter disorders, among the most common encountered, exhibit marked clinical variability and also may present as a
sudden death, a Reye's-like episode, or a
cardiomyopathy.
Jaundice or other evidence of hepatic dysfunction is the mode of presentation of another important group of
inborn errors of metabolism including
galactosemia,
hereditary tyrosinemia,
neonatal hemochromatosis, and a number of other conditions. A subset of lysosomal storage disorders may present very early with
coarse facial features, organomegaly, or even
hydrops fetalis. Specific patterns of dysmorphic features and congenital anomalies characterize yet another group of inherited metabolic disorders, such as
Zellweger syndrome and the
Smith-Lemli-Opitz syndrome. Each of these symptom complexes, and the appropriate evaluation of the affected infants, is discussed in more detail in this review.