Systemic organic acidemias: Identification, diagnosis, management and long term complications

Abstract Systemic organic acidemias are intoxication-type inborn errors of metabolism which can present in the neonatal period and beyond with metabolic acidosis, vomiting, and lethargy, and progress to coma and without adequate treatment ultimately death. There should be a low threshold for consideration of this family of disorders in individuals that present with the above symptoms, present with a sepsis-like picture, have developmental delay or intellectual disability, or develop disease-specific long term complications (e.g., cardiomyopathy seen in propionic acidemia, renal failure seen in the methylmalonic acidemias). Late diagnosis with intellectual disabilities or disease-specific complications are thought to becoming less common in areas with universal newborn screening since it includes many of these disorders and allows for early treatment and avoidance of severe presentations. In general, treatment in the acute setting focuses on decreasing toxin production by reversal of catabolism, removal of toxin precursors, use of toxin scavengers (e.g., levocarnitine to bind propionic acid in propionic acidemia) and attempting to improve enzyme function by using supra-physiologic doses of cofactors. Long term therapy has similar approaches.