[Inborn errors of metabolism in adults]

Abstract

We present a simplified classification of treatable inborn errors of metabolism (IEM) in three groups with a special focus on those disorders observed at adult age. Group 1 includes inborn errors (IE) of intermediary metabolism which give rise to an acute or chronic intoxication. It encompasses aminoacidopathies, organic acidurias (OA), urea cycle disorders (UCD), sugar intolerances, metal storage disorders and porphyrias. Clinical expression can be acute, systemic or involves a specific organ, it can strike in the neonatal period or later and intermittently from infancy to late adulthood. Most of these disorders are treatable and require the emergency removal of the toxin by special diets, extracorporeal procedures, cleansing drugs or vitamins. Group 2 includes IE of intermediary metabolism which affect the cytoplasmic and mitochondrial energetic processes. Cytoplasmic defects encompass those affecting glycolysis, glycogenosis, gluconeogenesis, creatine and pentose phosphate pathways; the latter are untreatable. Mitochondrial defects include respiratory chain disorders, Krebs cycle and pyruvate oxidation defects, mostly untreatable, and disorders of fatty acid oxidation and ketone bodies that are treatable. Group 3 involves cellular organelles and include lysosomal, peroxisomal, glycosylation, and cholesterol synthesis defects. Among these, some lysosomal disorders can be efficiently treated by enzyme replacement or substrate reduction therapies. Physicians can be faced with the possibility of a treatable IE in emergency, either in the neonatal period or late in infancy to adulthood, or as chronic and progressive symptoms, general (failure to thrive), neurological, or specific for various organs or systems. These symptoms and the simplified classification of IEM are summarized in seven tables.