생화학 및 분자유전학 검사로 진단한 한국인 조기유년기형 이염성백질이영양증 1례와 문헌 고찰
A Korean Patient with Early Juvenile Form of Metachromatic Leukodystrophy: Biochemical and Molecular Genetic Investigation
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
이염성백질이영양증은 arylsulfatase A 효소의 결핍으로 인해 발생하는 선천성 대사질환이다. 본 연구는 진행하는 신경학적 퇴행을 주소로 내원한 5세 환아를 대상으로 하였다. 환아는 뇌자기공명영상에서 양측 대뇌 백색질에 대칭적인 병변을 보였고 백혈구의 arylsulfatase A 효소 활성도는 8.0 nmol/hr/mg protein으로 감소되어 있었다(참고범위: 25-80 nmol/hr/mg protein). 중합효소연쇄반응-직접염기서열분석법으로 시행한 ARSA 유전자 검사에서는 기존에 질환 유발 변이로 알려진 c.449C>T (p.Pro150Leu) 변이와 새로운 돌연변이인 c.640G>A (p.Ala214Thr)가 확인되었다. 이에 임상 증상 및 생화학적, 영상의학적, 분자유전학적 검사 결과를 바탕으로 조기유년기형 이염성백질이영양증 환아 사례를 보고하는 바이다.
Abstract
Metachromatic leukodystrophy is an inherited lysosomal storage disorder caused by the deficiency of arylsulfatase A activity. The patient in this study, a 5-yr-old girl, presented with progressive psychomotor regression. An MRI image of her brain showed bilateral symmetrical demyelination. The arylsulfatase A activity in her leukocytes was decreased to 8.0 nmol/hr/mg protein (reference range, 25-80 nmol/hr/mg protein). Mutation analysis of ARSA, using PCR and direct sequencing, showed two heterozygote pathogenic variations of c.449C>T (p.Pro150Leu) and c.640G>A (p.Ala214Thr). In summary, we report a Korean patient with an early juvenile form of metachromatic leukodystrophy, who was diagnosed based on her clinical symptoms as well as by using biochemical, radiological, and molecular genetic investigations.
참고문헌 (10)
- Gieselmann V, "Metachromatic leukodystrophy--an update", Neuropediatrics, 41, pp.1~6 (2010)
- Biffi A, "Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation", Clin Genet, 74, pp.349~357 (2008)
- van Rappard DF, "Metachromatic leukodystrophy: disease spectrum and approaches for treatment", Best Pract Res Clin Endocrinol Metab, 29, pp.261~273 (2015)
- Cesani M, "Mutation update of ARSA and PSAP genes causing metachromatic leukodystrophy", Hum Mutat, 37, pp.16~27 (2016)
- Gieselmann V., "Metachromatic leukodystrophy: genetics, pathogenesis and therapeutic options", Acta Paediatr, 97, pp.15~21 (2008)
- Regis S, "Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity", Hum Genet, 110, pp.351~355 (2002)
- 한민제, "Biochemical and Genetic Analysis of Seven Korean Individuals With Suspected Metachromatic Leukodystrophy", Annals of Laboratory Medicine, 35(4), pp.458~462 (2015), 대한진단검사의학회
- 강동희, "Identification of a Novel Splicing Mutation in the ARSA Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy", Annals of Laboratory Medicine, 30(5), pp.516~520 (2010), 대한진단검사의학회
- Polten A, "Molecular basis of different forms of metachromatic leukodystrophy", N Engl J Med, 324, pp.18~22 (1991)
- Berger J, "Occurrence, distribution, and phenotype of arylsulfatase A mutations in patients with metachromatic leukodystrophy", Am J Med Genet, 69, pp.335~340 (1997)