Dietary intake, metabolic control and growth in patients with organic acidemia and urea cycle disorders

Abstract

Organic acidemias (OA) and urea cycle disorders (UCD) require lifelong natural dietary protein restriction and, when needed, amino acid mixtures. However, evidence on the long-term effects of these nutritional interventions on growth, dietary adequacy, and metabolic control remains limited. Few studies have systematically evaluated how disease-specific dietary patterns influence essential amino acid status and growth outcomes in these rare conditions. To assess dietary intake, plasma amino acid profiles, metabolic control, and growth outcomes in patients with MSUD, MMA/PPA, IVA, and UCD. In this 6-month prospective follow-up study, 81 patients aged 1–18 years (36 MSUD, 30 MMA/PPA, 6 IVA, 9 UCD) were evaluated. Anthropometry, 3-day dietary records (analyzed using BeBiS 8.2), and plasma amino acids were obtained at baseline and 6 months. Protein intake, P:E ratio, and amino acid adequacy were compared with disease-specific guidelines. Metabolic control parameters (ammonia, acid–base status, and branched-chain amino acids) were obtained from patient files. Statistical analyses included the Wilcoxon and Spearman correlation tests. Stunting and underweight were common across OA and UCD. In MSUD patients 47.2% were stunted and 36% were underweight at baseline; these rates were 44.4% and 52.2%, at 6 months, respectively. In MMA/PPA, the prevalence of underweight increased from 34.8% to 43.5%, and stunting from 43.3% to 50%. UCD patients showed persistent stunting (44.4%). IVA patients maintained normal growth. Despite adequate total protein intake, natural protein intake remained insufficient, and amino acid mixtures provided up to 75% of total protein in MSUD. PUFA and fiber intake were consistently inadequate in all groups. Chronic plasma isoleucine and valine deficiencies were prominent in MSUD and MMA/PPA. The P: E ratio was within recommended ranges but showed no association with height-for-age Z-scores. In MMA/PPA, pH was positively correlated with height-for-age (r = 0.410, p < 0.05), suggesting that acid–base status may be related to growth outcomes in MMA/PPA. Growth impairment is highly prevalent in OA and UCD despite intensive dietary management. Persistent essential amino acid deficiencies, reliance on synthetic amino acid mixtures, inadequate natural protein intake, and suboptimal dietary quality (low PUFA and fiber) may contribute to poor growth outcomes. Current disease-specific dietary guidelines show substantial variability, underscoring the need for standardized, evidence-based nutritional protocols. Patients should be closely monitored by a multidisciplinary metabolic team to optimize natural protein tolerance, essential amino acid balance, and long-term growth.

The authors' abstract, as published at the source. BMC Pediatrics, 2026 · DOI ↗