Clinical and Basic Research on Methylmalonic Acidemia and Related Cobalamin Disorders Including Natural History and Genetic Studies

What this Trial Is About

Methylmalonic acidemia MMA and related cobalamin metabolic disorders are inherited conditions affecting organic acid metabolism with varied causes and symptoms. Patients with certain types of MMA can experience serious complications like metabolic stroke, kidney failure, growth problems, and developmental delays. Current treatments have limitations, and organ transplantation is increasingly used. This research aims to understand the different forms of these disorders, their natural history, genetic causes, and to identify biomarkers and clinical outcomes to support future trials. Participants with MMA and cobalamin defects will undergo clinical evaluations including inpatient admissions lasting 4 to 5 days and outpatient visits. These include urine and blood tests, eye exams, imaging like MRIMRS, some skin biopsies, and developmental assessments. A subset of patients with organ transplants or unusual disease courses may have lumbar punctures to analyze cerebrospinal fluid. Evaluations may occur at the NIH Clinical Center, Childrens National Medical Center, UPMC Childrens Hospital of Pittsburgh, or remotely via telemedicine. During the study, participants will share medical history and undergo biochemical, molecular, and clinical assessments to better characterize disease progression. Researchers will analyze correlations between genetics, enzyme activity, and clinical features. Outcome measures focus on describing the natural history and complications over time. The research includes both in-person and remote participation options, accommodating a broad age range and varying disease severity.

Clinical and Laboratory Study of Methylmalonic Acidemia