Long-Term Management of Organic Acidurias (OA):   

The treatment strategies include the dietary restriction of precursor amino acids and the usage
of adjunctive compounds to dispose of toxic metabolites. The long-term care requires frequent
monitoring of growth, development and biochemical parameters. Unfortunately, OA is not UCD
(urea cycle disorders), ammonia maybe acutely damaging but remains a secondary problem in
OA. 
 
Literature Review:  

1.In a single center cohort study of MMA(methylmalonic academia) & PA(propionic academia)
on long term CGA, 8 patients show no decompensation episodes post CGA (carglumic
acid).  Ammonia concentration is reduced after CGA. (CGA dose: 50mg/kg/day) and protein
intake is increased 20 to 50%, weight gain is up to 6.5 kg after a month.  The level of ammonia,
lactate and uric acid is also reduced. The branched chain amino acid, such as isoleucine is
normalized.  
 
The conclusion is that the effect of CGA is not apparent in acute treatment
of hyperammonaemia, but becomes apparent after long term treatment. We believe CGA does
not alter hepatic propionyl Co-A, which inhibits glycine cleavage system. The CGA augments
ureagenesis normalizes branched-chain amino acid and shows the stabilization of cardiac
function. The CGA has beneficial effect on mitochondrial cardiomyopathy1.
 
2.One case report of PA on long term CGA.  Since initiation of NCG 100 mg/kg/day at 9 years of
age, a male Caucasian patient’s (now 15 years old) plasma ammonia level is decreased
significantly. (76 vs. 140 mcmol/L before NCG therapy, p < 0.005).  After NCG treatment at 9
years of age, only 2 episodes happen during 6 years vs. 6-10 episodes/year prior to NCG
initiation.  
 
The conclusion is that the chronic NCG use is associated with decrease in plasma ammonia level
and reduction in the frequency of metabolic decompensations.  No clinically significant adverse
reactions to the therapy, and no evidence of progression of multi-organ involvement. The
evidence from literatures shows that several reports have been published on the use of NCG in
secondary defects of urea cycle. Since 2005, more than 20 publications have been available on
clinical application of NCG in OAs (mainly in PA), and they demonstrate response and safety
during decompensation episodes of OAs2.  

 
3.The classic OAs can cause a series of cellular metabolic disruptions in the cells, and carglumic
acid can interfere in some of these mechanisms by exerting a rescue effect on urea