View clinical trials related to Methylmalonic Acidemia.
Filter by:The primary objective of this study is to evaluate the long-term safety of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.
To obtain short-term and long-term clinical safety information, in pediatric and adult patients with PA and MMA treated with Carbaglu®.
This is a study of mRNA-3705 in participants with isolated elevated methylmalonic acid (MMA) due to methylmalonyl-coenzyme A (CoA) mutase (MUT) deficiency. The main goal of the study is to assess safety, pharmacokinetics, and pharmacodynamics of mRNA-3705.
This is a prospective mixed-design study focused on the long-term management of propionic aciduria (PA) and methylmalonic aciduria (MMA) with N-carbamylglutamate (NCG) maintenance therapy. Treatment characteristics, clinical outcomes, and healthcare utilization data of patients diagnosed PA or MMA treated >6 months therapy with NCG are collected at baseline, 12 months, 18 months, 36 months and 54 months. Qualitative interviews with adult patients and caregivers are conducted >6 months after study enrollment to gain a better understanding of the disease burden and the treatment burden of patients and their families.
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.
Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Increasingly, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class (cblC, cblD, cblF, cblJ and cblX) and are also heterogenous, clinically and biochemically. The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature (hyper)homocysteinemia. Lastly, a group of patients can have increased methylmalonic acid and/or homocysteine in the blood or urine caused by variant(s)in recently identified (ACSF3) and unknown genes. In this protocol, we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last up to 4-5 days and involve urine collection, blood drawing, ophthalmological examination, radiological procedures, MRI/MRS, skin biopsies in some, and developmental testing. In a subset of patients who have or will receive renal, hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA, a lumbar puncture to examine CSF metabolites will be performed. In this small group of patients, CSF metabolite monitoring may be used to adjust therapy. The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies, query for genotype/enzymatic/phenotype correlations, search for new genetic causes of methylmalonic acidemia and/or homocysteinemia, identify new disease biomarkers and define clinical outcome parameters for future clinical trials. The population will consist of participants previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acidemia Association, Homocystinuria Network America and other national and international support groups. Most participants will be evaluated only at the NIH Clinical Center. However, if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol, that patient may enroll at the Children s National Medical Center (CNMC) site, pending approval by Dr Chapman, the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children s Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters.