Methylmalonic and propionic acidaemias: Management and outcome

Abstract

Organic acidurias comprise many various disorders. Methylmalonic aciduria (MMA) and propionic aciduria (PA) are the most frequent diseases and the two organic acidurias for which we have better knowledge of the long-term outcome. Comparing the outcome of patients born before and after 1990, it appears that better neonatal and long-term management have improved the survival rate. Less than 20% of the patients died in either the neonatal period or before the age of 10 years. However, most surviving patients showed poor nutritional status with growth retardation and about 40% present some kind of visceral or neurological impairment. The developmental outcome may have improved in MMA patients, with IQ higher than 75 in about 40% patients aged more than 4 years. Conversely, poor intellectual development is the rule in PA patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not necessarily prevented neurological and various visceral complications. These results emphasize the need for permanent metabolic follow-up whatever the therapeutic strategy.

Living with Intoxication-Type Inborn Errors of Metabolism: A Qualitative Analysis of Interviews with Paediatric Patients and Their Parents

“…Considerable progress in recent decades in the diagnosis and treatment of IT-IEM has resulted in a growing number of long-term survivors (de Baulny et al 2005;Batshaw et al 2014). The long-term medical care and support of patients and families requires insight into subjective psychosocial conditions and health-related quality of life (HrQoL) (Bullinger 2002).…”

Combined liver–kidney transplant for the management of methylmalonic aciduria: A case report and review of the literature

“…This organic aciduria causes significant morbidity in affected patients, including recurrent bouts of potentially life-threatening ketoacidosis and neurologic, hematologic, and renal impairment [1,2]. There are several different biochemical abnormalities involving methylmalonyl CoA mutase and its cofactor, cobalamin (vitamin B12), that can result in methylmalonic aciduria [2].…”

“…Progression to coma is not uncommon. If the patient does not succumb to the initial metabolic decompensation, failure to thrive, developmental retardation, renal failure and metabolic strokes follow [1,[3][4][5][6][7][8][9][10][11][12][13][14].…”

Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: Evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism

“…Patients deficient in methylmalonylCoA mutase (MUT) or adenosylcobalamin, the enzymatic cofactor, accumulate methylmalonic acid in their tissues and body fluids, and display secondary metabolic perturbations such as hyperglycinemia, hyperammonemia and intermittent hypoglycemia [1]. Despite meticulous dietary control, affected individuals exhibit extreme metabolic instability and suffer from severe complications, such as developmental delay, renal disease, pancreatitis and metabolic infarction of the basal ganglia [2][3][4][5]. The pathophysiology of these processes and disease complications remain poorly defined.…”