salicylates and Metabolism--Inborn-Errors

Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Diagnostic Errors; Humans; Metabolism, Inborn Errors; Reye Syndrome; Salicylates; Virus Diseases

Although the conditions that cause hypoglycemia in adults may also be present in infants and children, there are many entities unique to the pediatric age group. This reflects the delicate balance that exists in the newborn and young child between glucose production and utilization. During fasting in infants and children, hepatic glucose production is normally two to three times that of adults when expressed on the basis of weight. In the newborn and young infants, hypoglycemia usually presents with irritability, feeding difficulties, lethargy, cyanosis, tachypnea, and/or hypothermia rather than the typical adrenergic or neuroglucopenic symptoms seen in the adult. The hypoglycemia may be due to abnormalities in hormone secretion, substrate interconversion, or mobilization of metabolic fuels. The hypoglycemia associated with hyperinsulinemia may be transient neonatal, sustained, or drug-induced. Inborn errors of metabolism caused by enzymatic defects are responsible for hypoglycemia associated with abnormalities of production and utilization of metabolic fuels. These can involve carbohydrate, protein, and fat metabolism. In addition, there may be acquired or transient defects in carbohydrate metabolism secondary to other diseases or ingestion of certain substances. Finally ketotic hypoglycemia appears to be due to abnormalities in substrate availability. A variety of tests are useful for establishing the etiologic basis of the hypoglycemia, and the appropriate treatment depends upon the underlying cause.

Topics: Child; Endocrine System Diseases; Ethanol; Fatty Acids; Glucose; Heart Defects, Congenital; Homeostasis; Humans; Hyperinsulinism; Hypoglycemia; Infant; Infant, Newborn; Infant, Small for Gestational Age; Ketosis; Metabolism, Inborn Errors; Reye Syndrome; Salicylates

Reye syndrome has emerged as the quintessential example of an acute metabolic encephalopathy. The clinical presentation is quite stereotyped in most instances permitting rapid, accurate diagnosis and early therapeutic intervention. Intoxications and certain inborn metabolic errors may mimic Reye syndrome. All patients with a recurrent episode should be investigated thoroughly for evidence of a metabolic disorder associated with an enzyme deficiency. Notable in this regard are inborn errors affecting organic acid, ammonia, and carbohydrate metabolism. The mitochondrial disturbance in Reye syndrome is well documented but the pathophysiologic sequence linking the antecedent viral illness to the mitochondrial injury remains obscure. Recent identification of a spontaneous Reye-like illness in mice that is associated with a coronavirus infection may provide an opportunity to investigate this initial phase of the pathophysiologic sequence. The primary cerebral insult presumably derives from insufficient substrate availability and results in massive cytotoxic cerebral edema. Treatment revolves around the continuous infusion of hypertonic glucose and intermittent infusion of hypertonic mannitol. Management is designed to attenuate or avoid the various compounding metabolic insults during this critical period when the child is metabolically crippled. In 1963, the disorder was considered to be rare and almost irreversibly fatal. Today, the disorder is recognized to be more common, and the outcome is very satisfactory in 85 to 90 per cent of the cases. The role of aspirin remains very controversial. A number of studies suggest an association between this potential mitochondrial toxin and Reye syndrome, but a causal relationship has not been established. Until better understood, it seems advisable to avoid use of aspirin in children exhibiting symptoms suggestive of Reye syndrome.

Topics: Aflatoxins; Anesthesia, General; Animals; Child; Child, Preschool; Disease Models, Animal; Disease Outbreaks; Female; Ferrets; Fluid Therapy; Hospitalization; Humans; Hypertonic Solutions; Infant; Liver; Male; Metabolism, Inborn Errors; Mitochondria; Pentobarbital; Respiration, Artificial; Reye Syndrome; Salicylates; Succinylcholine; Virus Diseases

Topics: Adult; Barbiturates; Blood Protein Electrophoresis; Charcoal; Dextrans; Estrogens; Female; Gels; Humans; Iodine Isotopes; Male; Metabolism; Metabolism, Inborn Errors; Methods; Pregnancy; Salicylates; Thyroxine-Binding Proteins