Background Deficiency of 2-Methylbutyryl-CoA Dehydrogenase (also called Short/Branched-Chain Acyl-CoA Dehydrogenase or SBCAD) results from a defect in the metabolism of the branched-chain amino acid Isoleucine. The disorder was described in 2000 and only a few patients have been identified. The gene (SBCAD), located on chromosome 10, has been cloned and mutations identified in several patients.
Clinical
SBCAD Deficiency can have a highly variable presentation, ranging from poor feeding, lethargy, hypoglycemia, and metabolic acidosis at a few days of age to completely “asymptomatic” individuals. Those patients with symptoms have tended to display developmental delay, seizure disorder, or progressive muscle weakness in infancy and childhood. Long-term clinical follow-up, however, is lacking and the true clinical spectrum of the disease is yet to be determined. It is possible that some patients may have escaped onset of symptoms because they were not subjected to a metabolic stress.
Testing
Newborns can be screened for SBCAD Deficiency using tandem mass spectrometry analysis of a dried blood spot. The finding of elevated five-carbon acylcarnitine (C5) indicates either SBCAD Deficiency or Isovaleryl-CoA Dehydrogenase deficiency. To differentiate and make a diagnosis, further testing is required. Urine organic acid analysis from a patient suspected of SBCAD Deficiency will reveal elevation of 2-methylbutyrylglycine with lesser increases of 2-methylbutyrylcarnitine and 2-methylbutyric acid. Plasma free carnitine levels are low to normal. Identification of mutations in the SBCAD gene may permit prenatal diagnosis.
Treatment
Treatment of patients with SBCAD Deficiency involves a low protein diet, particularly reduction of the amino acid Isoleucine, and carnitine supplementation. During an acute episode, aggressive use of glucose and electrolytes will be necessary. Carnitine is indicated during acute episodes, and perhaps chronically in some patients. Because the diagnosis and therapy of SBCAD Deficiency 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
Andresen, B.S., Christensen, E., Corydon, T.J., et al. Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. Am J Hum Genet 67:1095, 2000. Gibson, K.M., Burlingame, T., Hogema, B., et al. 2-MethylButyryl-CoA dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism. Pediatr Res 47:830, 2000. Matern, D., He, M., Berry, S.A., et al. Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry. Pediatrics 112:74, 2003. 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. 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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