Methylmalonic Acidemia, Propionic Acidemia
Conditions
Keywords
methylmalonic acidemia, MMA, organic acidemia, mut deficiency, inborn errors of metabolism, mut0, mut-, PA, PCCA, PCCB, propionic acidemia
Brief summary
Longitudinal, exploratory, natural history study of patients with MMA due to mut deficiency and PA to characterize the changes in blood disease biomarkers over time and the frequency and severity of clinical events related to their disease.
Interventions
None listed
Sponsors
ModernaTX, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
MMA Only • Patient has a confirmed diagnosis of isolated MMA due to MUT deficiency (mut0 or mut-) based on the following criteria: * Elevated plasma/serum/DBS or urine methylmalonic acid levels * Presence of normal serum/plasma vitamin B12 and plasma homocysteine levels * Confirmed by molecular genetic testing. Genetic testing can be performed after the administration of informed consent if not available, however, molecular genetic results must be confirmed before the second study visit PA Only • Patient has a confirmed diagnosis of isolated PA based on the following criteria: * Elevated plasma/DBS/urine 2-MC and/or 3-HP * Elevated plasma/serum/DBS propionylcarnitine (C3) * Confirmed by genetic testing for mutations of the PCCA or PCCB genes. Genetic testing can be performed after the administration of informed consent if not available, however, molecular genetic results must be confirmed before the second study visit Both MMA and PA * Patient (and/or legally authorized representative as applicable to local regulations) is willing and able to comply with study-related assessments and activities * Patient or legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulation
Exclusion criteria
* Estimated GFR \<30 mL/min/1.73m2 based on age appropriate equations or patients who undergo chronic dialysis * The patient is pregnant or lactating at the time of screening. (Note: Patients who become pregnant during the study may remain in the study) MMA Only * Patients diagnosed with isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria PA Only * Patient has a confirmed diagnosis of multiple carboxylase deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in plasma methylmalonic acid levels (MMA only) | Baseline through 12 months |
| Frequency of disease related clinical events in enrolled participants (mut0 and mut- MMA patients) | Baseline through 12 months |
| Changes in plasma 2-MC levels (PA only) | Baseline through 12 months |
| Changes in plasma 3-HP levels (PA only) | Baseline through 12 months |
| Frequency of disease related clinical events in enrolled participants (PA patients) | Baseline through 12 months |
Countries
France, Spain, United Kingdom, United States
Outcome results
None listed