FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia.
Irini Manoli, Justin R Sysol, Madeline W Epping...
https://pubmed.ncbi.nlm.nih.gov/30518688Actively Recruiting
Age: 1Month - 115Years
All Genders
Healthy Volunteers
ID00078078
Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders
Led by National Human Genome Research Institute (NHGRI) · Updated on 2026-06-08
2275
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Methylmalonic acidemia (MMA) is a complex inherited disorder affecting organic acid metabolism, with various genetic causes and clinical symptoms. Patients with different classes of MMA and cobalamin metabolic defects can experience serious complications such as metabolic stroke, kidney failure, osteoporosis, and developmental delays. This research aims to better understand the range of symptoms, natural history, genetic factors, and outcomes of these conditions to support future clinical trials and improved care. Participants with MMA and related cobalamin disorders will undergo clinical evaluations during routine inpatient stays lasting 4-5 days or outpatient visits. These assessments include urine and blood tests, eye exams, imaging like MRI/MRS, developmental testing, and sometimes skin biopsies. Some patients who have undergone or will undergo organ transplants or have unusual disease courses may also have lumbar punctures to assess cerebrospinal fluid. Tissue collection and telemedicine options are also available for some individuals. During the study, participants will provide medical histories and undergo various examinations to collect biochemical and molecular data. Monitoring includes clinical evaluations, imaging, and developmental assessments to identify disease biomarkers and long-term complications. The study enrolls individuals from infancy through adulthood, with options for remote participation, and aims to describe the disease progression and correlations between genetics and symptoms over time.
CONDITIONS
Brief Title
Clinical and Laboratory Study of Methylmalonic Acidemia
Who Can Participate
Age: 1Month - 115Years
All Genders
Healthy Volunteers
Eligibility Criteria
You may qualify if you...
- Patients of any sex and ethnicity, aged over 1 month, with biochemical or genetic diagnosis of methylmalonic acidemia or cobalamin disorders
- Children under 2 years or under 12 kg may be reviewed for limited outpatient evaluations
- Patients who have had or will have transplantation surgery may enroll in tissue collection
- Pregnant women affected by the disorders or family members may enroll with some procedure restrictions
- Healthy volunteers aged 18 and over are eligible
You will not qualify if you...
- Medically unstable patients or those residing in hospital
- Patients requiring dialysis at least once per week and weighing less than 40 kg
- Patients currently treated for acute infection with antibiotics or showing metabolic symptoms
- Patients without regular metabolic, genetic, endocrine, or family physicians
- Patients metabolically unstable but not acutely ill
- Patients or families unable to follow testing and care recommendations before NIH visit
- Pregnant women excluded from tissue collection at UPMC Children's Hospital
- Individuals with kidney or liver disease, on special high-protein diets, or with severe claustrophobia or anxiety disorders
- Women who are pregnant (for healthy volunteer group)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Diagnostic Evaluation
Duration - 4 to 5 days
Participants undergo clinical and laboratory assessments including urine collection, blood draws, ophthalmological exams, radiological procedures, MRI/MRS, skin biopsies in some cases, and developmental testing to evaluate their condition.
1 inpatient admission and multiple outpatient evaluations over 4 to 5 days
Long-term Monitoring
Duration - Ongoing
Participants are observed over time to characterize the natural history, track long term complications, and correlate clinical, biochemical, and molecular parameters.
Follow-up visits as needed depending on individual clinical status
Trial Site Locations
Total: 3 locations
1
Children's National Medical Center
Washington D.C., District of Columbia, United States, 20010
Completed
2
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
3
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
Actively Recruiting
Loading map...
Research Team
J
Jennifer L Sloan, Ph.D.
C
Charles P Venditti, M.D.
How is the study designed?
Study Type
OBSERVATIONAL
Masking
N/A
Allocation
N/A
Model
N/A
Primary Purpose
N/A
Number of Arms
1
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here
Published Research Related To This Trial
A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias.
Irini Manoli, Jennifer G Myles, Jennifer L Sloan...
https://pubmed.ncbi.nlm.nih.gov/26270765Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.
Irini Manoli, Justin R Sysol, PamelaSara E Head...
https://pubmed.ncbi.nlm.nih.gov/382710991-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA).
Irini Manoli, Alexandra R Pass, Elizabeth A Harrington...
https://pubmed.ncbi.nlm.nih.gov/33820958Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.
Irini Manoli, Abigael Gebremariam, Samantha McCoy...
https://pubmed.ncbi.nlm.nih.gov/37243446Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia.
Elizabeth A Harrington, Jennifer L Sloan, Irini Manoli...
https://pubmed.ncbi.nlm.nih.gov/26790480The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers.
Marianna Caterino, Randy J Chandler, Jennifer L Sloan...
https://pubmed.ncbi.nlm.nih.gov/26672496Propofol administration in patients with methylmalonic acidemia and intracellular cobalamin metabolism disorders: a review of theoretical concerns and clinical experiences in 28 patients.
Yiouli P Ktena, Trygg Ramstad, Eva H Baker...
https://pubmed.ncbi.nlm.nih.gov/25985870