Protocol Number: 04-HG-0127

Title:

Clinical and Basic Investigations of Methylmalonic Acidemia (MMA)

Number:

04-HG-0127

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

-Skin biopsy for cell culture (cells to grow in the laboratory for future testing). For this procedure, an area of skin is numbed with an anesthetic such as lidocaine. A 4-mm diameter circular area is then removed using a sharp punch and scissors. The wound is dressed and usually heals within a week.

-Photographs of the face and body (wearing underwear) to help track growth and appearance.

-Ultrasound of the kidneys

-Hand x-ray to determine bone age

-Dual energy x-ray absorptionometry (DEXA) scan to assess bone density. For the DEXA scan, the patient lies still on a table while the spine and hip are scanned using a small amount of radiation.

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.

Sponsoring Institute:

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

MMA patients of any gender and ethnicity age 2-70 years 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 tothe protocol based upon metabolic parameters and clinical history.

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. Other criteria include 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/weekand 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.

Special Instructions: Currently Not Provided

Keywords:

Renal Function

Growth Hormone

Metabolic Disease

Cobalamin

Vitamin B12

Methylmalonic Acidemia

Recruitment Keywords:

Methylmalonic Acidemia

MMA

Metabolic Disease

Conditions:

Amino Acid Metabolism

Inborn Errors

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Levy HL, Albers S. Genetic screening of newborns.

Annu Rev Genomics Hum Genet. 2000;1:139-77. Review.

Chace DH, Kalas TA, Naylor EW. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet. 2002;3:17-45. Epub 2002 Apr 15. Review.

Bobik TA, Rasche ME. Identification of the human methylmalonyl-CoA racemase gene based on the analysis of prokaryotic gene arrangements. Implications for decoding the human genome. J Biol Chem. 2001 Oct 5;276(40):37194-8. Epub 2001 Jul 31.

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Bethesda, Maryland 20892. Last update: 10/23/2004