ABSTRACT
PURPOSE: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disoder of beta oxidation of fatty acids and characterized by episodic hypoglycemia, vomiting, convulsion, encephalopathy, apnea, and sudden death related to fasting or infection resembling Reye syndrome or sudden infant death syndrome. In acute stage, mortality rate is very high and survivors have significant risk of developmental disability and chronic somatic illness. However, the high mortality and morbidity can be totally prevented by appropriate dietary management on the basis of early and accurate diagnosis. Recently, a single point mutation (A985G) in the MCAD gene has been described that accounts for most of MCAD deficiency. The prevalence of MCAD deficiency shows marked racial differences. And population-based DNA screening for this potentially fatal disorder might be justified in countries with high frequency of the mutation. The prevalence of A985G mutation in the MCAD gene was studied in neonates using Guthrie cards for neonatal screening. METHODS: Dried blood spots on Guthrie cards originally used for neonatal screening programs obtained from 500 live newborn babies born in a private obstetric clinic or Seoul Red Cross Hospital in Seoul during the period from Jan. 1, 1995 to Jul. 31, 1995 were collected. DNA was extracted from the dried blood spots, and a segment of the MCAD gene was amplified from the DNA using polymerase chain reaction technique. The PCR products were electrophoresed on a polyacrylamide gel after treatment of a restriction enzyme, NcoI. And the restriction pattern was analyzed with ethidium bromide staining of the gel. RESULTS: The PCR was successful with all DNAs from Guthrie cards. And the A to G transition at nucleotide position 985 in the MCAD gene was not demonstrated in any of the specimen. Conlusions : 1) The frequency of A985G mutation in the MCAD gene is extremely low in Korean population. 2) The methodology used in this study can be applied to population-based molecular genetic studies for other hereditary diseases.
Subject(s)
Humans , Infant, Newborn , Acyl-CoA Dehydrogenase , Apnea , Death, Sudden , Developmental Disabilities , Diagnosis , DNA , Ethidium , Fasting , Fatty Acids , Genetic Diseases, Inborn , Genetics, Population , Hypoglycemia , Mass Screening , Molecular Biology , Mortality , Neonatal Screening , Point Mutation , Polymerase Chain Reaction , Prevalence , Red Cross , Reye Syndrome , Seizures , Seoul , Sudden Infant Death , Survivors , VomitingABSTRACT
PURPOSE: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disoder of beta oxidation of fatty acids and characterized by episodic hypoglycemia, vomiting, convulsion, encephalopathy, apnea, and sudden death related to fasting or infection resembling Reye syndrome or sudden infant death syndrome. In acute stage, mortality rate is very high and survivors have significant risk of developmental disability and chronic somatic illness. However, the high mortality and morbidity can be totally prevented by appropriate dietary management on the basis of early and accurate diagnosis. Recently, a single point mutation (A985G) in the MCAD gene has been described that accounts for most of MCAD deficiency. The prevalence of MCAD deficiency shows marked racial differences. And population-based DNA screening for this potentially fatal disorder might be justified in countries with high frequency of the mutation. The prevalence of A985G mutation in the MCAD gene was studied in neonates using Guthrie cards for neonatal screening. METHODS: Dried blood spots on Guthrie cards originally used for neonatal screening programs obtained from 500 live newborn babies born in a private obstetric clinic or Seoul Red Cross Hospital in Seoul during the period from Jan. 1, 1995 to Jul. 31, 1995 were collected. DNA was extracted from the dried blood spots, and a segment of the MCAD gene was amplified from the DNA using polymerase chain reaction technique. The PCR products were electrophoresed on a polyacrylamide gel after treatment of a restriction enzyme, NcoI. And the restriction pattern was analyzed with ethidium bromide staining of the gel. RESULTS: The PCR was successful with all DNAs from Guthrie cards. And the A to G transition at nucleotide position 985 in the MCAD gene was not demonstrated in any of the specimen. Conlusions : 1) The frequency of A985G mutation in the MCAD gene is extremely low in Korean population. 2) The methodology used in this study can be applied to population-based molecular genetic studies for other hereditary diseases.
