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Acidosis is often found in children without metabolic diseases and may be due to fasting associated with anorexia, vomiting,diarrhea, and dehydration in the course of a viral illness. In thisnormal result of fasting, the blood glucose is relatively low; amild acidosis and ketonuria may be present. Administrationof carbohydrate restores balance. Severe ketosis may also bethe result of disorders of ketone utilization such as ketothiolase deficiency or SCOT (succinyl-CoA:3 ketoacid CoA transferase) deficiency. In these conditions, which frequently present in thecontext of fasting, infection with fever, or decreased intake secondary to vomiting and diarrhea, hypoglycemia may be profound; the ketosis resolves slowly. As ketone bodies accumulate,cyclic vomiting may ensue. Ketotic hypoglycemia is a common condition in which tolerance for fasting is impaired. Symptomatic hypoglycemia with seizures or coma occurs when the childencounters a catabolic stress. The stress may be significant (viralinfection with vomiting) or minor (a prolongation by severalhours of the normal overnight fast). Ketotic hypoglycemia firstappears in the second year of life and occurs in otherwise healthychildren. It is treated by frequent snacks and the provision ofglucose during periods of stress. The pathophysiology is poorlyunderstood (see Chapter 172). Although ketonuria is a normalresponse to prolonged (not overnight) fasting in older infantsand children, it indicates metabolic disease in neonates. A high anion gap metabolic acidosis with or without ketosis suggests a metabolic disorder (Table 51-6). Although ketone productionmay be reduced in some fatty acid oxidation disorders, the presence of ketonuria does not exclude this group of disorders.
Disorders Associated with Dysmorphic Findings
Congenital malformations or dysmorphic features are not intuitively thought of as symptoms and signs of inborn errors. Conditions that cause congenital malformations include carbohydrate-deficient glycoprotein syndrome, disorders of cholesterol biosynthesis (Smith-Lemli-Opitz syndrome), disorders of copper transport (Menkes syndrome, occipital horn syndrome), maternal phenylketonuria syndrome, glutaric aciduria II (also called multiple acyl-coenzyme A [CoA] dehydrogenase deficiency), and several storage diseases.
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Storage disorders are caused by accumulation of incompletely metabolized macromolecules. This storage often occurs in subcellular organelles, such as lysosomes. The glycogen storage diseases and mucopolysaccharide disorders are examples of storage disorders.
Gaucher and Niemann-Pick diseases GSD IV (slowly evolving) Crigler-Najjar disease Rotor, Dubin-Johnson syndromes
GSD, Glycogen storage disease.
The assessment begins with a careful history (family and individual) and clinical evaluation. Clinical laboratory testing can define the metabolic derangement (Table 51-7). The results generate a differential diagnosis and a list of more specific laboratory testing to confirm the diagnosis.
The combination of symptoms and abnormal clinical laboratory findings demands urgent metabolic evaluation. Ametabolic emergency often presents with vomiting, acidosis,hypoglycemia, ketosis (or lack of appropriate ketosis), inter-current infection, anorexia/failure to feed, lethargy proceeding to coma, and hyperventilation or hypoventilation. Clinicalevaluation should focus on the cardiac, renal, neurologic, anddevelopmental assessment as well as looking for changes inmental status, seizures, abnormal tone, visual symptoms,poor developmental progress, global developmental delay,loss of developmental milestones (regression), cardiomyopathy, cardiac failure, cystic renal malformation, and renal tubular dysfunction.