Hereditary metabolic diseases in the intensive care unit: investigations, diagnostic and therapeutic approaches

Abstract

Inborn errors of metabolism (IEMs) are caused by deficiencies in enzymes and other proteins involved in cell metabolism. Numerous IEMs are curable and thus diagnosis is mandatory before the occurrence of any irreversible neurological injury. IEMs may be responsible for intensive care unit (ICU) admission of patients with unexplained coma or encephalopathy, at any age from infancy to late adulthood. These acute late-onset presentations are often triggered by apparently non-specific external factors including benign fever episodes, prolonged exercise, prolonged fasting, and surgery. Disorders of energy metabolism and “endogenous intoxications” (syndromes leading to hyperammonemia, hyperhomocysteinemia, porphyria, aminoacidopathy, and organic aciduria) represent the two major categories of IEMs. In these settings, in addition to brain magnetic resonance imaging, the most useful metabolic investigations are measurements of blood concentrations of lactate, pyruvate, and ammonia, followed by plasma concentrations of aminoacids and homocystein as well as urine concentrations of organic acids, porphyrins, and porphobilinogen. Interpretation of these biochemical tests and the consequent treatments of assessed metabolic abnormalities require specific expertise found in reference centers.