Malonic Aciduria

Background
Malonic Aciduria is a rare disorder caused by deficiency of Malonyl-CoA Decarboxylase (MCD). MCD is an enzyme that catalyzes the degradation of malonyl-CoA. Malonyl-CoA is a substrate for fatty acid synthesis and it also regulates oxidation of fatty acids by controlling their uptake into mitochondria. MCD may therefore regulate fatty acid synthesis and oxidation by affecting intracellular malonyl-CoA levels, but its function is not completely known. The gene for MCD, located on chromosome 16, has been cloned and mutations identified in patients with MCD deficiency.

Clinical

The presentation of malonic aciduria due to MCD deficiency is variable, ranging from an acute neonatal onset to later in childhood. Patients have symptoms of developmental delay, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, and ketosis. Hypertrophic cardiomyopathy can be seen.

Testing

Newborn screening of a dried blood spot using tandem mass spectrometry reveals elevation of malonyl-carnitine, which is characteristic of the disorder. Confirmatory studies include urine organic acids, which show elevations in malonic acid, methylmalonic acid, and possibly other organic acids. Studies on cultured fibroblasts confirm a decrease in MCD activity. Identification of mutations in the MCD gene may be useful for genetic counseling.

Treatment

There is limited experience in managing this rare disorder. Dietary modification to increase the amount of calories from carbohydrate relative to fat has been effective in improving metabolic abnormalities. Extended fasting should be avoided. Carnitine supplementation has been beneficial in some patients.

Because the diagnosis and therapy of Malonic Aciduria is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.

Inheritance

This disorder most often follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder.

As with all genetic diseases, genetic counseling may be appropriate to help families understand recurrence risks and ensure that they receive proper evaluation and care.

References

FitzPatrick DR, Hill A, Tolmie JL, et al. The molecular basis of malonyl-CoA decarboxylase deficiency. Am J Hum Genet 65:318-326, 1999.

MacPhee, et.al.; Malonyl coenzyme A decarboxylase deviciency. Arch. Dis. Child. 69:433-436, 1993.

Santer R, Fingerhut R, Lassker U, et al. Tandem mass spectrometric determination of malonylcarnitine: diagnosis and neonatal screening of malonyl-CoA decarboxylase deficiency. Clin Chem 49:660-662, 2003.

Sweetman L, Williams JC. Branched chain organic acidurias. The Metabolic and Molecular Basis of Inherited Disease. 8th Edition. Scriver, Beaudet, et al. McGraw-Hill. pg. 2155-2157, 2001

Web Sites
SaveBabies.org
Site established and maintained by parents of newborns affected with a rare genetic defect, with information for parents and professionals and links to other informative sites.

National Newborn Screening and Genetics Resource Center
Provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

Organic Acidemia Association
Advocacy site for families affected by organic acidopathies.

Disclaimers
The analyses conducted by PerkinElmer Genetics produce results that can be used by qualified physicians in the diagnosis of disorders described herein. Evidence of these conditions will be detected in the vast majority of affected individuals; however, due to genetic variability, age of the patient at the time of specimen collection, quality of the specimen, health status of the patient, and other variables, such conditions may not be detected in all affected patients. PerkinElmer Genetics makes no warranty whatsoever, express or implied, including any warranty as to accuracy, completeness or timeliness, concerning the information contained herein, and you should not assume that such information is complete or the most up-to-date information available. PerkinElmer Genetics shall not be liable for any loss, claim or damages caused in whole or in part by our provision of, or your use of, any of the information contained herein. As a general statement, this information was drawn from published literature and is not drawn from our patient population or screening experience. The information contained herein is not intended to be a substitute for professional medical advice and should not be used for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions.

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