Home
Search
Study Topics
Glossary
|
|
|
|
|
|
Sponsored by: |
National Human Genome Research Institute (NHGRI) |
---|---|
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00078078 |
This study will evaluate patients with methylmalonic acidemia (MMA) to learn more about the genetic causes of the various types of this inherited metabolic disorder and the medical complications associated with it. People with MMA may have problems with learning and development and kidney malfunctioning. They can become seriously ill, sometimes with little warning. There is no cure for any MMA, but special diets and vitamin therapies are used for treatment.
Patients between 2 and 70 years of age with MMA may be eligible for this study. Participants are admitted to the NIH Clinical Center for 4-5 days each year for 5-10 years for the following tests and procedures:
Any patient who becomes seriously ill during the evaluation may be cared for at the NIH or transferred to another hospital if it is deemed advisable.
...
Condition |
---|
Amino Acid Metabolism Inborn Errors |
Study Type: | Observational |
Study Design: | Prospective |
Official Title: | Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders |
Estimated Enrollment: | 600 |
Study Start Date: | February 2004 |
Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cb1A, cb1B 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. Rarely, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered intracellular metabolism of vitamin B12 produces another group of disorders that feature methylmalonic acidemia as well (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class - cobalamin C (cb1C), D and F - and are also heterogenous, clinically and biochemically. The genetic disorders underlying cb1E and cb1G feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine. Lastly, a group of patients who have increased methylmalonic acid and/or homocysteine in the blood caused by mutation(s) in unknown genes exist.
In this protocol, we will clinically evaluate patients with methymalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last 4-5 days and involve urine collection, blood drawing, ophthalmologic 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 MMA therapy.
The study objectives will be to further delineate the spectrum of phenotypes associated with these enzymopathies, query for genotype/enzymatic/phenotype correlations and search for new genes in rare families that have evidence for an unknown class of methylmalonic acidemia and/or homocysteinemia. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acid Association. All patients will be evaluated at the NIH clinical center. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters.
Ages Eligible for Study: | 2 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Patients of any gender and ethnicity age 2 and older are eligible to enroll in this protocol. Patients will be diagnosed based on a determination of MMA and homocysteine levels in plasma and urine. Most will have their complementation class known or pending. Some patients who have not yet had this laboratory test will be admitted to the protocol based upon metabolic parameters and clinical history. This latter category of patients might include individuals with a suspected genetic but unknown class of MMA.
EXCLUSION CRITERIA:
Patients will be excluded if they cannot travel to the NIH because of their medical condition or are less than 2 years of age. The PI may decline to enroll a patient for other reasons. Other criteria that may lead to exclusion include, for example, residing in a hospital, sub-optimal metabolic control as determined by Dr. Venditti's review of the laboratory data, any patient who requires dialysis once or more/week and weighs less than 40 kg, any patient who is being treated for an intercurrent infection with antibiotics or has evidence of an acute infection, and any patient who does not have a regular/local metabolic, genetic or endocrine physician and/or a family physician, pediatrician, or internist.
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Study ID Numbers: | 040127, 04-HG-0127 |
Study First Received: | February 18, 2004 |
Last Updated: | December 12, 2008 |
ClinicalTrials.gov Identifier: | NCT00078078 |
Health Authority: | United States: Federal Government |
Vitamin B12 Methylmalonic Acidemia Hyperhomocysteinemia |
Methylmalonic Acidemia MMA Metabolic Disease |
Metabolic Diseases Methylmalonic acidemia Hyperhomocysteinemia |
Hydroxocobalamin Vitamin B 12 Metabolic disorder |