The Prevalence of A985G Mutation in Medium Chain Acyl-Coenzyme A Dehydrogenase(MCAD) Gene in Neonates Determined from Guthrie Card

Lee, Baeck Hee; Park, Hye Won; Park, Moon Soo; Park, Ho Jin; Choi, Yong; Cheong, Hae Il

Original Article

Journal of the Korean Pediatric Society 1997;40(12):1645-1650.
Published online December 15, 1997.

The Prevalence of A985G Mutation in Medium Chain Acyl-Coenzyme A Dehydrogenase(MCAD) Gene in Neonates Determined from Guthrie Card

Baeck Hee Lee¹, Hye Won Park², Moon Soo Park³, Ho Jin Park⁴, Yong Choi⁵, Hae Il Cheong⁵

¹Department of Pediatrics, Dankook University Hospital
²Department of Pediatrics, Seoul City Boramae Hospital
³Department of Pediatrics, Sungkyunkwan University Kangbuk Samsung Hospital
⁴Department of Pediatrics, Seoul Red Cross Hospital
⁵Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea

Guthrie Card를 이용한 신생아의 Medium Chain Acyl-Coenzyme A Dehydrogenase(MCAD) 유전자내 A985G 돌연변이 빈도에 대한 연구

이백희^¹^, 박혜원^²^, 박문수^³^, 박호진^⁴^, 최용^⁵^, 정해일^⁵

^¹단국대학교 의과대학 소아과학교실
^²서울시립보라매병원 소아과
^³성균관대학교 의과대학 강북삼성병원 소아과학교실
^⁴서울적십자병원 소아과
^⁵서울대학교 의과대학 소아과학교실

Abstract

Purpose
: Medium chain acyl-CoA dehydrogenase(MCAD) deficiency is an autosomal recessive disoder of β 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.

Key Words: MCAD deficiency, A985G mutation, MCAD gene, Guthrie card, Population genetics