Combined Malonic and Methylmalonic Aciduria

Last update 08 May 2025

Basic Info

Synonyms

CMAMMA, CMAMMA - combined malonic and methylmalonic aciduria, COMBINED MALONIC AND METHYLMALONIC ACIDURIA

+ [6]

Introduction

A rare inborn error of metabolism with characteristics of elevation of malonic acid (MA) and methylmalonic acid (MMA) in body fluids, with higher levels of MMA than MA. The disease presents in childhood with metabolic acidosis, developmental delay, dystonia and failure to thrive or in adulthood with seizures, memory loss and cognitive decline.

Clinical Trials associated with Combined Malonic and Methylmalonic Aciduria

NCT01289158

/ Unknown statusNot ApplicableIIT

Combined Malonic and Methylmalonic Aciduria (CMAMMA): Gene Identification and Outcome Study

The investigators are interested in learning more about the changes found in the condition called "Combined elevation of Malonic and MethylMalonic Acid, or CMAMMA. " Malonic, or MA and MethylMalonic, or MMA, are acids formed from the breakdown of protein under normal conditions. However, in the condition called CMAMMA there is an increase of these acids in the blood and urine, which is not normal.
Some people with high MA and MMA in their blood and urine have a serious disease, starting as a baby or young child that includes heart disease and problems in learning. These people have changes in a special enzyme called Malonyl CoA Decarboxylase (MCD). Other people who have a high level of MA and MMA do not have any obvious illness. The investigators are not sure why they have high levels of MA and MMA and why they are not sick.
The goal of this study is to learn more about why some people have a high level of MA and MMA and to make sure there are no medical problems as a result of these high levels. The investigators also want to find out which gene and enzyme cause the high levels of MA and MMA.

Start Date01 Feb 2011

Sponsor / Collaborator

Centre universitaire de santé McGill

100 Clinical Results associated with Combined Malonic and Methylmalonic Aciduria

100 Translational Medicine associated with Combined Malonic and Methylmalonic Aciduria

0 Patents (Medical) associated with Combined Malonic and Methylmalonic Aciduria

Literatures (Medical) associated with Combined Malonic and Methylmalonic Aciduria

29 Jul 2022·BrainQ1 · MEDICINE

ZBTB11 dysfunction: spectrum of brain abnormalities, biochemical signature and cellular consequences

Q1 · MEDICINE

Article

Author: Backe, Paul Hoff ; Misceo, Doriana ; Fattahi, Zohreh ; Mørkrid, Lars ; Valayannopoulos, Vassili ; Najmabadi, Hossein ; Frengen, Eirik ; van Karnebeek, Clara D ; Sumathipala, Dulika ; Nilsen, Hilde ; Einarsen, Ingunn Holm ; Strømme, Petter ; Lüders, Torben ; Venditti, Charles P ; Sheng, Ying ; Kahrizi, Kimia ; van den Heuvel, Lambert ; Wevers, Ron A ; Sloan, Jennifer L ; Guerrero-Castillo, Sergio

AbstractBi-allelic pathogenic variants in ZBTB11 have been associated with intellectual developmental disorder, autosomal recessive 69 (MRT69; OMIM 618383). We report five patients from three families with novel, bi-allelic variants in ZBTB11. We have expanded the clinical phenotype of MRT69, documenting varied severity of atrophy affecting different brain regions and described combined malonic and methylmalonic aciduria as a biochemical manifestation.As ZBTB11 encodes for a transcriptional regulator, we performeded chromatin immunoprecipitation–sequencing targeting ZBTB11 in fibroblasts from patients and controls. Chromatin immunoprecipitation–sequencing revealed binding of wild-type ZBTB11 to promoters in 238 genes, among which genes encoding proteins involved in mitochondrial functions and RNA processing are over-represented. Mutated ZBTB11 showed reduced binding to 61 of the targeted genes, indicating that the variants act as loss of function. Most of these genes are related to mitochondrial functions. Transcriptome analysis of the patient fibroblasts revealed dysregulation of mitochondrial functions. In addition, we uncovered that reduced binding of the mutated ZBTB11 to ACSF3 leads to decreased ACSF3 transcript level, explaining combined malonic and methylmalonic aciduria.Collectively, these results expand the clinical spectrum of ZBTB11-related neurological disease and give insight into the pathophysiology in which the dysfunctional ZBTB11 affect mitochondrial functions and RNA processing contributing to the neurological and biochemical phenotypes.

01 Apr 2021·Molecular Genetics & Genomic MedicineQ4 · MEDICINE

Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria

Q4 · MEDICINE

ArticleOA

Author: Gabriel, Marie Cosette ; Al‐Kouatly, Huda B. ; Rice, Stephanie M. ; Venditti, Charles P. ; Sloan, Jennifer L. ; Mossayebi, Matthew H.

AbstractBackgroundExpanded carrier screening (ECS) utilizes high‐throughput next‐generation sequencing to evaluate an individual's carrier status for multiple conditions. Combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency is a rare inherited disease included in such screening panels. Some cases have been reported with metabolic symptoms in childhood yet other cases describe a benign clinical course, suggesting the clinical phenotype is not well defined.Methods/Case ReportClinical and laboratory findings during the prenatal period were obtained retrospectively from medical records.ResultsA 37‐year‐old nulliparous woman and her partner were each identified as carriers of ACSF3 variants and presented at 9 weeks gestation for prenatal genetic consultation. The couple received extensive genetic counseling and proceeded with chorionic villus sampling at 11 weeks gestation. Subsequent analysis confirmed that the fetus inherited both parental ACSF variants. The couple was devastated by the results and after reviewing options of pregnancy continuation and termination, they decided to terminate the pregnancy. Following this decision, the patient was diagnosed with acute stress disorder.ConclusionThis case highlights how expanded carrier screening adds complexity to reproductive decision‐making. Stronger guidelines and additional research are needed to direct and evaluate the timing, composition, and implementation of ECS panels.

01 Dec 2020·Orphanet Journal of Rare Diseases

Brain metabolism and neurological symptoms in combined malonic and methylmalonic aciduria

Letter

Author: Tucci, Sara

AbstractCombined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism which has been proposed being a benign condition. However, older patients may present with neurological manifestations such as seizures, memory problems, psychiatric problems and/ or cognitive decline. In fibroblasts from CMAMMA patients we have recently demonstrated a dysregulation of energy metabolism with increased dependency on β-oxidation for energy production. Because of the inability of the brain to rely efficiently on this pathway to retrieve the required energy to a great extent, we hypothesize an alternative disease-causing mechanism that does not only include the accumulation of the metabolites malonic and methylmalonic acids. Here, we suggest a novel hypothesis on the possible pathophysiological mechanism responsible for the development of neurological symptoms in the long-run.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Combined Malonic and Methylmalonic Aciduria

Basic Info

Related

Analysis