Affiliations: Section of Genetics and Metabolism, Children's
National Medical Center, Washington, DC, USA
Note: [] Corresponding author: Kimberly A. Chapman, 111 Michigan Ave, NW,
Suite 1950, Washington, DC, 20010, USA. Tel.: +1 202 476 6287; Fax: +1 202 476
5650; E-mail: [email protected]
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.
