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- $Unique_ID{BRK03415}
- $Pretitle{}
- $Title{Acidemia, Methylmalonic}
- $Subject{Acidemia, Methylmalonic Methylmalonic Acidurias Ketotic
- Hyperglycinemia Propionic Acidemia}
- $Volume{}
- $Log{}
-
- Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders,
- Inc.
-
- 427:
- Acidemia, Methylmalonic
-
- ** IMPORTANT **
- It is possible the main title of the article (Methylmalonic Acidemias is
- not the name you expected. Please check the SYNONYMS listing on the next
- page to find alternate names and disorder subdivisions covered by this
- article.
-
- Synonyms
-
- Methylmalonic Acidurias
-
- Information on the following diseases can be found in the Related
- Disorders section of this report:
-
- Ketotic Hyperglycinemia
- Propionic Acidemia
-
- General Discussion
-
- ** REMINDER **
- The information contained in the Rare Disease Database is provided for
- educational purposes only. It should not be used for diagnostic or treatment
- purposes. If you wish to obtain more information about this disorder, please
- contact your personal physician and/or the agencies listed in the "Resources"
- section of this report.
-
-
- Methylmalonic Acidemias are one type of organic acidemia. All known
- organic acidemias are inherited as autosomal recessive traits. They are
- caused by an enzymatic defect in the metabolism of one amino acid. This
- results in an abnormally high level of acid in the blood and body tissues and
- concomitant metabolic acidosis. Acutely, drowsiness, coma, and seizures may
- occur. Mental retardation is a long-term consequence. The disorders may be
- caused either by a deficiency of the enzyme methylmalonyl CoA mutase,
- methylmalonyl racemase, or of adenosylcobalamin synthetic enzymes. Excretion
- of methylmalonate, a product of amino acid metabolism, in the urine is
- abnormally high.
-
- Symptoms
-
- The onset of the Methylmalonic Acidemias usually occurs during the first few
- months of life. Symptoms may include lethargy, failure to thrive, recurrent
- vomiting, acidosis, dehydration, respiratory distress, diminished muscle
- tone, developmental retardation, seizures and/or an enlarged liver.
-
- Laboratory findings include an abnormally high amount of methylmalonic
- acid in the blood and urine. Metabolic acidosis also occurs. Elevated
- levels of ketone bodies such as acetone in the blood (ketonemia) or in the
- urine (ketonuria) may develop. An elevated level of ammonia in the blood
- (hyperammonemia) may also be present. Excessive levels of the amino acid
- glycine in the blood (hyperglycinemia) and in the urine (hyperglycinuria) is
- found. The concentration of white blood cells, blood platelets and red blood
- cells may be lower than normal. Low blood sugar (hypoglycemia) may also
- occur.
-
- Causes
-
- The Methylmalonic Acidemias are inherited as autosomal recessive traits.
- (Human traits including the classic genetic diseases, are the product of the
- interaction of two genes for that condition, one received from the father and
- one from the mother. In recessive disorders, the condition does not appear
- unless a person inherits the same defective gene from each parent. If one
- receives one normal gene and one gene for the disease, the person will be a
- carrier for the disease, but usually will show no symptoms. The risk of
- transmitting the disease to the children of a couple, both of whom are
- carriers for a recessive disorder, is twenty-five percent. Fifty percent of
- their children will be carriers, but healthy as described above. Twenty-five
- percent of their children will receive both normal genes, one from each
- parent and will be genetically normal.)
-
- Related Disorders
- Symptoms of the following disorders are similar to those of Methylmalonic
- Acidemias. Comparisons may be useful for a differential diagnosis.
-
- Ketotic Hyperglycinemia is a group of hereditary protein metabolism
- disorders. In each case, a defective enzyme prevents the breakdown of
- certain amino acids and lipids. High levels of the amino acid glycine and
- ketones accumulate in the blood and urine. Clinically, affected infants have
- feeding difficulties and developmental, neurological, digestive, and
- metabolic problems, as well as increased susceptibility to infections.
- Often, complications can be avoided with early treatment. The disorders are
- very rare, with only a few individual cases reported. Methylmalonic Acidemia
- is a form of Ketotic Hyperglycinemia. (For more information on this
- disorder, choose "Ketotic Hyperglycinemia" as your search term in the Rare
- Disease Database.)
-
- Propionic Acidemia is a very rare genetic form of Ketotic
- Hyperglycinemia. This disorder is caused by a deficiency of the enzyme
- propionyl CoA carboxylase, one of the enzymes necessary in the process of
- breaking down amino acids. (For more information on this disorder, choose
- "Propionic Acidemia" as your search term in the Rare Disease Database.)
-
- Affected Population
-
- The Methylmalonic Acidemias occur at a rate of 1 in 50,000 to 1 in 100,000
- live births.
-
- Therapies: Standard
-
- The diet of children with Methylmalonic Acidemias must be carefully
- controlled. Treatment includes a low-protein diet and avoidance of the
- amino acids isoleucine, valine, and threonine. To assure a balanced diet,
- certain medical foods must be fed to affected children. Pharmacologic doses
- of vitamin B12 are indicated in the B12-responsive variants.
-
- Genetic counseling is recommended for the families of children with
- Methylmalonic Acidemias.
-
- Therapies: Investigational
-
- This disease entry is based upon medical information available through March
- 1990. Since NORD's resources are limited, it is not possible to keep every
- entry in the Rare Disease Database completely current and accurate. Please
- check with the agencies listed in the Resources section for the most current
- information about this disorder.
-
- Resources
-
- For more information on Methylmalonic Acidemias, please contact:
-
- National Organization for Rare Disorders (NORD)
- P.O. Box 8923
- New Fairfield, CT 06812-1783
- (203) 746-6518
-
- Organic Acidemia Association
- 522 Lander St.
- Reno, NV 89512
- (702) 322-5542
-
- British Organic Acidemia Association
- 5 Saxon Rd.
- Ashford, Middlesex TW15 1QL
- England
-
- Research Trust for Metabolic Diseases in Children
- Golden Gates Lodge, Weston Rd.
- Crewe CW1 1XN, England
- Telephone: (0270) 250244
-
- For genetic information and genetic counseling referrals, please contact:
-
- March of Dimes Birth Defects Foundation
- 1275 Mamaroneck Avenue
- White Plains, NY 10605
- (914) 428-7100
-
- Alliance of Genetic Support Groups
- 35 Wisconsin Circle, Suite 440
- Chevy Chase, MD 20815
- (800) 336-GENE
- (301) 652-5553
-
- References
-
- CLINICAL HETEROGENEITY IN COBALAMIN C VARIANT OF COMBINED HOMOCYSTINURIA AND
- METHYLMALONIC ACIDURIA: G.A. Mitchell, et al.; Journal Pediatr (March 1986:
- issue 108,3). Pp. 410-415.
-
- THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et
- al., eds.; McGraw-Hill, 1983. Pp. 486-493.
-
-