Encephalopathy inborn errors

Hyperammonemias are caused by inborn errors of ureagenesis and organic acidemias, liver immaturity (transient hyperammonemia of the newborn), and liver failure (hepatic encephalopathy). Neonatal hyperammonemias are characterized by vomiting, lethargy, lack of appetite, seizures, and coma. The underlying defects can be identified by appropriate laboratory measurements (e.g., assessment of metabolic acidosis if present and characterization of organic acids, urea cycle intermediates, and glycine). 

Biochemical disease involves a departure from the normal in some body component, e.g. an enzyme, a structural protein or a membrane transport mechanism. Some biochemical diseases are almost entirely environmental in origin, e.g. lead encephalopathy, but at present attention is largely directed to genetically determined conditions—the inborn errors of metabolism and other molecular diseases. In some cases it is the interaction between genotype and external environment which brings about the signs and symptoms, in others, such as the gangliosidoses, no modification of the external environment can appreciably alter the course of the disease. 

However, encephalopathies with a metabohc basis tend to be the most problanatic for infants or children, with functional outcomes dependent upon timely and pradent interventions. Three varieties of metabolic encephalopathy in children are discussed here. The first two are closely related. Inborn (genetic) errors of metabolism can present in the newborn as severe encephalopathy from hyperammonemia alone. When a metabolic error presents months to years later, a degree of hepatic insufficiency may complicate the metabolic derangement. In acute or fulminant hepatic failure of any etiology (i.e., infections, drug-induced, toxin-related), the rise in serum ammonia may be only moderate but other factors contribute to the ensuing encephalopathy, which may be devastating within days. 

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