대한유전성대사질환학회지 (Journal of The Korean Society of Inherited Metabolic disease)

대한유전성대사질환학회 (The Korea Society of Inherited Metabolic Disease)
권호 표지

선천성 부신 과형성증(21-hydroxylase 결핍)의 신생아 선별 검사 후 진단 알고리즘

A Diagnostic Algorithm after Newborn Screening for 21-hydroxylase Deficiency

  • 조성윤 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 고정민 (서울대학교 어린이병원 소아청소년과) ;
  • 이경아 (연세대학교 강남세브란스병원 진단검사의학과)
  • Cho, Sung Yoon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ko, Jung Min (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Lee, Kyung-A (Department of Laboratory Medicine, Yonsei University College of Medicine)
  • 발행 : 2016.08.31
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⟨ 이전 논문 다음 논문 ⟩

초록

선천성 부신 과형성증 중 가장 흔한 21-hydroxy-lase deficiency (21-OHD)는 신생아 선별검사에서 17-hydroxyprogesterone (17-OHP)의 증가로 조기 진단이 가능하다. 17-OHP가 애매하게 증가되는 경우에는 ACTH 자극 검사가 필요하며, 이 검사는 nonclassical (NC형) 21-OHD 진단의 gold standard이다. 전형적인 임상 증상이 없는 경우, 예를 들어 남성화가 심하지 않은 여아, 경한 simple virilizing (SV)형 남아나 신생아 선별 검사에서 발견되지 않을 수 있는 NC형 환자의 경우, 분자유전학적 검사가 진단에 도움을 줄 수 있으며, 이는 예후 에측 및 유전 상담에도 도움이 된다. 미숙아와 저체중 출생아의 경우는 17-OHP가 위양성을 보이기 쉬우므로 출생 주수나 출생 체중에 따른 cutoff 값 설정이 필요하다. 높은 위양성률을 극복하기 위해 기존 RIA방법에 비해 최근 LC-MS/MS가 민감도와 특이도를 높이는 검사로 주목 받고 있다. 21-OHD 신생아 선별 검사의 효율성을 높이기 위해서는 SW형 남아를 조기에 발견하고, 여아에서 성별 결정을 조기에 올바르게 하고, NC형 환자를 찾아내고, 미숙아/저체중 출생아/아픈 신생아에서 위양성률을 낮추어서 불필요한 재검 및 경제적/심리적 부담을 최소화 하기 위한 노력이 필요하다. 무엇보다 21-OHD가 임상적으로 확실하게 의심되는 경우에는 확진 검사에 앞서 적절한 치료가 조기에 시작되어야 한다. 저자들은 본 종설에서 21-OHD의 신생아 선별 검사 후 진단 알고리즘에 대해 최신 문헌들에 근거하여 가이드라인을 제시하는 바이다.

21-hydroxylase deficiency (21-OHD), most common form of congenial adrenal hyperplasia, is categorized into classical forms, including the salt-wasting (SW) and the simple virilizing (SV) types, and nonclassical (NC) forms based on the severity of the disease. Newborn screening for 21-OHD has been performed in Korea since 2006. $17{\alpha}$-hydroxyprogesterone (17-OHP) is a marker for 21-OHD and is measured using a radioimmunoassay or a fluoroimmunoassay. Premature and low birth weight infants are likely to give false positive 17-OHP findings, therefore, cutoff values for these infants should be determined based on gestational weeks or birth weight. ACTH simulation test is helpful when the 17-OHP shows equivocal increase, and it is gold standard for diagnosis of NC type. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Molecular analysis of CYP21A2 is useful for confirming diagnosis of mild SV or NC type, predicting prognoses, and genetic counseling. In order to make newborn screening for 21-OHD more efficient, early detection of boy with SW type, early determination of girl with ambiguous genitalia, detection of NC type, and overcoming of false positive in premature and low birth weight infants should be considered. Above all, early treatment should be started when the patient is suspected as having 21- OHD clinically before confirming the diagnosis to prevent adrenal crisis. Here, author reviewed recent articles of guideline and proposed guideline for 21-OHD.

키워드

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