Baumgartner MR, et al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014 Sep 2;9:130.
Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100’000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA and cardiomyopathy mainly in PA. Except for vitamin B12 responsive forms of MMA the outcome remains poor despite the existence of apparently effective therapy with a low protein diet and carnitine. This may be related to under recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity.
Grünert SC, et al. Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients. Orphanet J Rare Dis. 2013 Jan 10;8:6.
Propionic acidemia (PA) is a rare autosomal recessively inherited inborn error of propionate metabolism. The biochemical defect involves the conversion of propionyl-coenzyme A (propionyl-CoA) to methylmalonyl-coenzyme A (methylmalonyl-CoA) by the mitochondrial enzyme propionyl-CoA carboxylase (PCC, EC 220.127.116.11). Thus, the metabolism of branched-chain amino acids, odd-numbered fatty acids, cholesterol side chains, thymine and uracil is impaired.
Most patients with this disorder present in the neonatal period with severe metabolic acidosis and hyperammonemia. However, late presentations with predominantly neurological symptoms as well as asymptomatic individuals have also been described [1–3]. With progression of the disease, patients are prone to complications affecting the neurologic, cardiologic, hematologic, immunologic and gastrointestinal system. As underlined in the proceedings of a recently held consensus conference on PA, the understanding of the disease course in PA is rather limited, with most information deriving from case reports and small retrospective case series . Although few authors have reported data on larger groups of patients [2,5–9] information on the long-term outcome of affected individuals is still limited.