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

Frequently Asked Questions About Methylmalonic Acidemia (MMA)

What is this study about?

This study will evaluate patients with methylmalonic acidemia (MMA) and cobalamin disorders to learn more about the genetic causes of these inherited metabolic disorders and the medical complications associated with them. People with MMA may have difficulty with growth and development, neurological problems such as strokes, seizures and low muscle tone, kidney problems, poor vision, and metabolic instability causing them to become seriously ill, sometimes with little warning. There is no cure for any genetic MMA syndrome, but special diets, medication and vitamin therapies are used for treatment.

Why should I join the study?

People join research studies for many reasons. Three common reasons include:

1. Altruism. This simply means "a regard for others." For example, why do many people donate blood? Most of the time, the blood helps a stranger in need, and not anyone known to the donator. For many people, it feels good to help others, and that is reason enough. The same is true for a research study. There may be no direct benefit to you, but by helping doctors learn about MMA, you are helping the wider community with MMA.
   
   
2. Learning. It is not unusual for a person with a rare disease (like MMA) to know more about their illness than many doctors! Joining a research study is a chance to spend time with doctors with a special interest in MMA. There is a lot of time to ask questions, to learn "what's new" and to better understand MMA.
   
   
3. Advice. People join research studies to seek medical advice from doctors with special expertise and interest in their disease. This can range from confirmation of a diagnosis to guidance on a new problem. It is important to remember that doctors involved in research (such as those at NIH) work with, but cannot replace, your "regular doctor". However, we may be able to find doctors, and other medical professionals and support groups in your local area with experience with MMA

New information, treatments and in the future, a cure, for methylmalonic acidemia will only come from patients with MMA and their families working together with doctors. Animal models of the disease (like mice) are helpful up to a point. But there is no replacement for studying the disorder in a human being.

What we are trying to learn with the study?

The study seeks to learn more about the genetic causes of the various types of these inherited metabolic disorders and the medical complications associated with them by clinically evaluating patients with methymalonic acidemia and cobalamin (vitamin B12) metabolic defects. By better understanding the complications, we may gain insight into what causes them. This knowledge may help guide the development of new therapies and provide more precise ways to assess how effective current medical regimens are working.

What are we NOT trying to do?

1. We are NOT testing any new medication or procedure to treat or cure MMA.
2. At the National Institutes of Health (NIH), we are interested in research. Although we are happy to provide advice for people enrolled in our study, we are not able to "take over" the long-term care of a person with MMA
3. To enroll in our study, a person needs a confirmed diagnosis of MMA. We are not able to provide a "first time" diagnosis or regular metabolic care.

Who is eligible to participate?

To be in our study, a person must:

1. Be between 2 and 70 years of age.
2. Be able to travel to and be admitted to the NIH Clinical Center in Bethesda, Maryland for 4 to 5 days each year for 5 to 10 years.
3. Have a diagnosis of mut, cblA, cblB, cblC, cblD, or cblF type MMA based on complementation status determination in cultured fibroblasts and/or genetic testing. We are also interested in evaluating patients with elevated homocysteine due to cblE and cblG deficiencies. Some patients who have not yet had these laboratory tests will be admitted to the protocol based upon metabolic parameters, such as MMA and/or homocysteine levels in the blood and/or urine, and clinical history. Dr. Venditti will determine patient eligibility when definitive testing has not been performed.

There are some reasons that may prevent you from joining the study. Patients will be excluded if they cannot travel to the NIH because of their medical condition or are less than 2 years of age. Other criteria that may lead to exclusion include: sub-optimal metabolic control as determined by Dr. Venditti's review of the laboratory data; residing in a hospital; 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.

What is involved in the study?

In this study, we will clinically evaluate patients with methymalonic acidemia and cobalamin (vitamin B12) metabolic defects. We will define and characterize a patient population, obtain cells and urine, perform mutation analysis in known genes, and search for the causative genes when the molecular basis of the complementation class is uncertain.

Routine admissions will last 4 to 5 days and occur every year. Some patients may be seen on the outpatient clinic but most will be inpatient admissions. Evaluations will involve urine collection, blood drawing, ophthalmologic examination, radiological procedures such as abdominal ultrasound and brain MRI, and developmental and neurological testing. A skin biopsy will be only performed if it has not been done or there is a need for a repeat study. In a subset of patients who have or will receive kidney, liver or liver kidney transplants or have an unusual variant or clinical course, a lumbar puncture to examine CSF metabolites will be recommended. In this small group of patients, CSF metabolite monitoring may be used to adjust MMA therapy. All testing is optional for the participants.

What is the cost of the study?

The visits and all testing are free and there is no cost to you, your family or your insurance company for this study.

What about travel?

We will pay for most of your travel expenses. If you live locally (near the NIH) we will give you some money for meals and provide lodging if necessary. If you live further away, we will pay for your transportation to NIH (plane, car mileage, train, etc), lodging, and give you some money for meals. Travel must be arranged by NIH.

Will I get paid for joining the study?

No, participants in the study do not receive any compensation other than travel and lodging expenses.

How do I enroll?

You may contact Dr. Charles Venditti at venditti@mail.nih.gov or Jennifer Sloan at jsloan@mail.nih.gov.

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Last Reviewed: April 20, 2012