Acidosis The differential diagnosis of metabolic acidosis is broad (see Chapter 100 Renal and Electrolyte Emergencies ) but IEMs must be considered in patients with unexplained or greater-thanexpected metabolic acidosis Clinical manifestations of acidosis are nonspecific and include vomiting and tachypnea Primary metabolic acidosis is diagnosed by low pH, low PCO , and low bicarbonate An elevated anion gap (>16 mmol/L), which is characteristic of acute metabolic crisis with many IEMs, helps distinguish among causes of metabolic acidosis An elevated anion gap with a normal chloride usually reflects excess acid production, most often of lactate, ketone bodies, and/or other organic acids Organic acidemias are characterized by metabolic acidosis, usually severe, with marked ketonuria, with or without hyperammonemia or hypoglycemia In neonates believed to have pyloric stenosis, the diagnosis of IEM, particularly an organic acidemia, should be considered if the patient has metabolic acidosis rather than metabolic alkalosis Fatty acid oxidation disorders may also present with metabolic acidosis, but usually with hypoglycemia and absent ketones or hypoketosis The IEMs in which a primary lactic acidosis is the cause of the metabolic acidosis include disorders of gluconeogenesis and mitochondrial disorders of oxidation In patients with metabolic acidosis, concentration of serum ammonia and glucose, and presence or absence of urine ketones and reducing substances will also help direct further metabolic workup Plasma amino acids, acylcarnitines and urine organic acids, and acylglycines should be measured Measurement of serum lactate, pyruvate, ketones, and organic acids may also be helpful