Methylmalonic Acidemia (MMA) is a severe and rare condition that affects how the body turns food into energy. In people with MMA, the body is missing or has a very low activity of a specific protein (an enzyme called methylmalonyl-CoA mutase (MMUT)) needed to break down certain proteins and fats in everyday food. Because this process does not work properly, a harmful substance called methylmalonic acid builds up in the blood and tissues, causing damage in the body.
Most people with MMA have an altered MMUT gene, which affects the enzyme methylmalonyl-CoA mutase. MMA often appears in infancy or early childhood, but some people are diagnosed later.
MMA affects approximately 1 in every 100,000 babies born and primarily impacts the liver, brain and kidneys. MMA poses significant challenges as it can result in complications such as dangerous acid levels in the blood, problems with the brain and nerves, visions problems, problems with how the pancreas, liver, and the kidneys work, as well as growth and development delays.
The main purpose of this observational study that tracks how the disease develops over time is to gather necessary data and evidence to confirm which signs in the body and blood test results can reliably show disease activity related to MMA. These confirmed signs and blood test results will be used for future research into developing new treatments for MMA. The data will be collected from participants with severe symptoms with and without liver transplant.
Aged ≤16 years at screening visit
With or without previous liver (or combined liver/kidney) transplantation at time of screening (note: number of transplanted participants capped at n=15) 3. Confirmed laboratory diagnosis of Isolated MMA caused by mutations in the MMUT gene (NOTE: if a historical genetic mutational analysis report was available at Screening visit but was not from a CLIA/ISO15189 approved laboratory, a confirmatory sample will be taken during the study. However the original lab report will be adequate for study eligibility consideration)..
Serum methylmalonic acid (sMMA) level of >100 µmol/L at the Screening visit
An unscheduled ER visit, hospitalization or requirement for use of the sick day diet regimen in the 12 months prior to the screening visit
Participant/parent/legal guardian/caregiver not willing to consent to participate
Current participation in another interventional or therapeutic study
Prior participation in a gene therapy clinical trial including mRNA therapy
Participants who, in the opinion of the Site Investigator, would be unable or unsuitable to participate in the demands of the study, for example but not limited to participants unable to travel to protocol study visits or participants under palliative care.
The participants will come from the participating hospital where they are routinely follow up for their disease and their routine care
Cohort
Prospective
Not listed
Evaluation of disease progression using biochemical biomarkers
Change over time in biomarkers to evaluate disease progression and/or organ transplantation.
Evaluate metabolic stability
Number of metabolic decompensation episodes (MDEs) assessed longitudinally to evaluate disease progression, with or without organ transplantation
Evaluate disease trajectory outcomes
Disease outcomes assessed longitudinally to evaluate disease progression, with or without organ transplantation
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