Methylmalonic and propionic aciduria

AbstractMethylmalonic and propionic aciduria (PA) are the most frequent forms of branched‐chain organic acidurias. These autosomal recessive disorders result from deficient activity of methylmalonyl‐CoA mutase and propionyl‐CoA carboxylase, respectively. Clinically, acute or chronic neurologic signs are caused by the accumulation of toxic compounds proximal to the metabolic block. Phenotype varies from severe neonatal‐onset forms with high mortality and poor outcome to milder forms with a later onset. In both cases the clinical course is dominated by the risk of relapses of life‐threatening episodes of metabolic decompensation and of severe organ failure. Despite improvement of treatment, the overall outcome remains disappointing with no major differences between the two diseases. The diagnosis is based on the presence of characteristic compounds in body fluids as detected by organic acid analysis in urine and acylcarnitine profile in blood. Therapy is based on low‐protein high‐energy diet, carnitine supplementation, and metronidazole. Some patients with methylmalonic aciduria (MMA) respond to pharmacological doses of vitamin B12. Given the poor long‐term prognosis, liver transplan