Organic acidurias in adults: late complications and management

J Inherit Metab Dis. 2018 Sep;41(5):765-776. doi: 10.1007/s10545-017-0135-2. Epub 2018 Jan 15.


Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry-based newborn screening programmes, in particular for isovaleric aciduria and glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary treatment with low protein intake or reduced intake of the precursor amino acid(s), carnitine supplementation, cofactor treatment (in responsive patients) and nonadsorbable antibiotics is commonly used for maintenance treatment. Emergency treatment options with high carbohydrate/glucose intake, pharmacological and extracorporeal detoxification of accumulating toxic metabolites for intensified therapy during threatening episodes exist. Diagnostic and therapeutic measures have improved survival and overall outcome in individuals with OADs. However, it has become increasingly evident that the manifestation of late disease complications cannot be reliably predicted and prevented. Conventional metabolic treatment often fails to prevent irreversible organ dysfunction with increasing age, even if patients are considered to be "metabolically stable". This has challenged our understanding of OADs and has elicited the discussion on optimized therapy, including (early) organ transplantation, and long-term care.

Keywords: Adults; Clinical phenotype; Glutaric aciduria type 1; Isovaleric aciduria; Management; Methylmalonic aciduria; Organic acidurias; Outcome; Propionic aciduria.

Publication types

  • Review

MeSH terms

  • Adult
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Amino Acid Metabolism, Inborn Errors / mortality
  • Amino Acid Metabolism, Inborn Errors / therapy*
  • Amino Acid Metabolism, Inborn Errors / urine
  • Brain Diseases, Metabolic / metabolism
  • Brain Diseases, Metabolic / urine
  • Glutaryl-CoA Dehydrogenase / deficiency
  • Glutaryl-CoA Dehydrogenase / metabolism
  • Glutaryl-CoA Dehydrogenase / urine
  • Humans
  • Infant, Newborn
  • Methylmalonic Acid / metabolism
  • Neonatal Screening
  • Predictive Value of Tests
  • Propionates / metabolism
  • Tandem Mass Spectrometry


  • Propionates
  • Methylmalonic Acid
  • Glutaryl-CoA Dehydrogenase

Supplementary concepts

  • Glutaric Acidemia I