Trial reportGenetics in medicine : official journal of the American College of Medical Genetics2016
A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias.
Trial report in Genetics in medicine : official journal of the American College of Medical Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00078078 (Clinical and Basic Investigations of Methylmalonic Acidemia), which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.Journal of inherited metabolic disease · 2021Guideline
- Sarcopenia in Pediatric Intoxication Type Inborn Errors of Metabolism: A Frequent and Underrecognized Condition.Journal of inherited metabolic disease · 2026Article
- Prolonged In Vitro Exposure to Methylmalonic Acid Induces Inflammation, Glutamate Metabolism Disruption, and Alters Functional Gene Expression in C6 Astroglial Cells.Neurotoxicity research · 2026Article
- [Occurrence status and treatment strategies of abnormal growth and development in children with methylmalonic acidemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Simplifying supplementation in MSUD: tolerance and acceptability of liquid valine and isoleucine supplements in maple syrup urine disease.Orphanet journal of rare diseases · 2026Article
- Generation of an isogenic human induced pluripotent stem cell line with a mutant propionyl-CoA carboxylase α subunit.Orphanet journal of rare diseases · 2026Article
- Nutritional Management in Severe Methylmalonic and Propionic Acidemias: How Much Medical Food Is Too Much?Journal of inherited metabolic disease · 2026Article
- Natural Protein-Restricted Diets and Their Impact on Linear Growth in Patients with Propionic and Methylmalonic Acidemia: A Systematic Review.Journal of personalized medicine · 2025Review
- Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.Human molecular genetics · 2025Article
- Review
- Caregiver's experiences with a mobile-based educational program and its impact on dietary treatment compliance of children with methylmalonic acidemia: an online survey.Orphanet journal of rare diseases · 2025Article
- Role of carglumic acid in the long-term management of propionic and methylmalonic acidurias.Orphanet journal of rare diseases · 2024Review
- Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.JCI insight · 2024Article
- Prevalence of propionic acidemia in China.Orphanet journal of rare diseases · 2023Review
- Acyl-CoA dehydrogenase substrate promiscuity: Challenges and opportunities for development of substrate reduction therapy in disorders of valine and isoleucine metabolism.Journal of inherited metabolic disease · 2023Article
- Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- New insights into the pathophysiology of methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families.Iranian biomedical journal · 2023Article
- Systemic gene therapy for methylmalonic acidemia using the novel adeno-associated viral vector 44.9.Molecular therapy. Methods & clinical development · 2022Article
- Review of neuropsychological outcomes in isolated methylmalonic acidemia: recommendations for assessing impact of treatments.Metabolic brain disease · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMedical foods for methylmalonic acidemias (MMAs) and propionic acidemias contain minimal valine, isoleucine, methionine, and threonine but have been formulated with increased leucine. We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of patients with MMA ascertained via a natural history study.
methodsCross-sectional anthropometric and body-composition measurements were correlated with diet content and disease-related biomarkers in 61 patients with isolated MMA (46 mut, 9 cblA, and 6 cblB).
resultsPatients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein (mut(0): 99.45 ± 32.05% RDA). However, 85% received medical foods, in which the protein equivalent often exceeded complete protein intake (35%). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. Weight- and height-for-age z-scores correlated negatively with the leucine-to-valine intake ratio (r = -0.453; P = 0.014; R(2) = 0.209 and r = -0.341; P = 0.05; R(2) = 0.123, respectively).
conclusionIncreased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. Medical foods for propionate oxidation disorders need to be redesigned and studied prospectively to ensure efficacy and safety.Genet Med 18 4, 386-395.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.