Clinical Trial: Clinical and Laboratory Study of Methylmalonic Acidemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders

Brief Summary:

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:

  • Medical history, physical examination, eye examination
  • Consultations from dentists and specialists in the nervous system, digestive tract, endocrine, and kidney, as needed.
  • 24-hour urine collection to examine for methylmalonic acid, other acids, sugar, and proteins for measuring kidney function.
  • Blood test to assess liver and thyroid function, blood counts and blood chemistries, methylmalonic acid levels, and for genetic tests and basic research studies.
  • Blood test to measure growth hormone production. For this test, a very small amount of blood is collected overnight (every 20-30 minutes from 8:00 PM to 8:00 AM) through an intravenous catheter (plastic tube placed in a vein). The total amount of blood drawn is approximately 1 tablespoon. Patients who have stopped growing or whose weight does not permit collection of 1 tablespoon of blood do not undergo this procedure.
  • Frequent blood pressure measurements, including overnight monitoring
  • 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. 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 as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class cobalamin C (cblC), D and F 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. 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, 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 C
    Sponsor: National Human Genome Research Institute (NHGRI)

    Current Primary Outcome:

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    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: February 18, 2004
    Date Started: February 17, 2004
    Date Completion:
    Last Updated: April 20, 2017
    Last Verified: February 24, 2017