Abstract
Background/Objectives: Propionic acidemia (PA) and methylmalonic acidemia (MMA) affect methionine, threonine, valine (Val), and isoleucine (Ile) (MTVI) metabolism, leading to the production of highly neurotoxic organic acids. Treatment involves a diet restricted in natural proteins and supplemented with a protein substitute (PS) with traces of MTVI. The aim was to analyze natural protein and PS intake in relation to linear growth impairment in individuals with PA and MMA. Methods: We followed the PRISMA protocol. We considered articles published between 1970 and 2025. We determined the eligibility criteria for selecting articles and evaluated the quality. Results: Thirteen studies were selected: two case reports, eight longitudinal, three cohorts, and one cross-sectional. Articles demonstrated that natural protein intake decreases with age, consistent with previous reports, underscoring the need for PS supplementation to meet protein requirements. Subjects with PA and non-responsive MMA had greater restriction of natural proteins, and the majority required PS; a higher PS intake was negatively correlated with a higher height-for-age (H/A) z-score. When analyzing the ratio of protein to energy (P:E), a negative correlation was found between the intake of natural proteins and energy, and a positive correlation with H/A z-score (p-value < 0.05). Supplementation with PS increased leucine levels, causing an imbalance with MTVI amino acids. This imbalance led to the paradoxical need to supplement L-Val and L-Ile, both propiogenic amino acids. As a result, a decrease in the H/A z-score was observed, particularly in PA and non-responsive MMA. Responsive MMA tolerated more natural proteins, received a lower intake of PS, and had a better H/A z-score. Conclusions: Restriction of natural proteins and PS is associated with a lower H/A z-score, primarily in subjects with PA and non-responsive MMA.