Nutritional Management in Severe Methylmalonic and Propionic Acidemias: How Much Medical Food Is Too Much?

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inherited metabolic disorders affecting valine and isoleucine catabolism. Long-term therapy mainly involves dietary protein restriction. An amino acid mixture (AAM, medical food) free of the precursor amino acids is frequently used, especially when protein intake does not reach World Health Organization (WHO) recommendations. However, its clinical impact on disease control and patient outcomes remains unclear. Our study aimed to retrospectively review the dietary prescriptions in a cohort of vitamin B12-unresponsive MMA and PA patients and to analyze their impact on clinical and laboratory parameters. Clinical data, anthropometric measurements and dietary prescriptions were collected from the patients' medical and dietary files. We included 71 patients (38 MMA and 33 PA). Fifty-nine percent of the patients' dietary prescriptions did not reach the safe WHO-recommended daily total protein intake. Among these, 28% included AAM supplementation versus 62% in the group of patients that met the WHO recommendations (p < 0.001). AAM was associated with a decrease in mean plasma concentrations of isoleucine and valine. These plasma amino acid concentrations were corrected by isoleucine and valine supplementation; however, leucine/isoleucine and leucine/valine ratios remained elevated in comparison to patients without AAM. Nutritional and clinical scores were worsened by AAM supplementation. We found that MMA/PA patients receiving AAM tend to have altered plasma amino acid concentrations, raising concerns about potential long-term deleterious consequences of AAM. We recommend prioritizing natural protein intake over AAM when possible, and if not, to carefully monitor and moderately supplement valine and isoleucine to prevent deficiencies.