Med 156:315–320, 2002
Holmes LB, Westgate MN: Inclusion and exclusion criteria for malforma tions in newborns exposed to potential teratogens, Birth Defects Research (Part A) 91:807–812, 2011
Kliegman RM, Stanton B, St. Geme J, et al: Nelson Textbook of Pediatrics, 19th ed, Philadelphia, 2011, Saunders . Online Mendelian Inheritance in Man (website): http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim
Optimal outcomes for children with inborn errors of metabolism (IEMs) depend upon recognition of the signs and symptoms of metabolic disease, and prompt evaluation and referral to a center familiar with their management. Delay in diagnosis may result in end organ damage including progressive neurologic injury or death.
With the exception of phenylketonuria (PKU), and medium chain acyl-CoA dehydrogenase (MCAD) deficiency, most metabolic disorders are individually rare, having an incidence of less than 1 per 100,000 births in the United States. When considered collectively, the incidence may approach 1 in 800 to 2500 births (Table 51-1) with the prevalence of a confirmed metabolic disorder detected by newborn screening in 1 in 4000 live births (about 12,500 diagnoses each year) in the United States. This is comparable with the 1 in 1000 infants who have early-onset bacterial sepsis and the 1 in 3000 infants who have invasive group B streptococcal infections.
IEMs are frequent causes of sepsis-like presentations, mental retardation, seizures, sudden infant death, and neurologic impairment; 20% of admissions to a regional children’s hospital are for genetic disorders.
Metabolic disorders can be classified using a variety of schemes based on the clinical presentation, including the age of onset, the tissues or organ systems involved, the defective metabolic pathways, or the subcellular localization of the underlying defect. These classification schemes have differing utility when considering approach to diagnosis, management, and screening strategies. The clinical presentation and longterm prognosis have the most bearing on management of children with genetic metabolic disorders.
Genetic metabolic disorders result from the deficiency of an enzyme, its cofactors, or biochemical transporters that lead to the deficiency of a required metabolite, the buildup of a toxic compound, or a combination of both processes (Fig. 51-1, Table 51-2). Understanding which of these mechanisms is involved and if the effects are systemic or restricted to the local tissue enables a rational approach to diagnosis, therapy, and management.
Available @ StudentConsult.com
The signs and symptoms of an inborn error are diverse andcan involve any organ system. The presentation varies amongage groups. Inborn errors of metabolism often present a fewhours to weeks after birth, often mimicking late-onset sepsis.Infants who survive the neonatal period without developingrecognized symptoms often experience intermittent illness separated by periods of being well. While pursuing the evaluationof the specific clinical presentations (e.g., the approach to thesick newborn, irritable child, or child with liver dysfunction),the hypoglycemic and intoxicating (encephalopathy) metabolicdisorders should be considered in all neonates presenting withlethargy, poor tone, poor feeding, hypothermia, irritability, orseizures. In most cases these should be evaluated for by assessment of plasma ammonia, blood glucose, and anion gap (Fig. 51-2). Significant ketosis in the neonate is unusual and suggests