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깲뜡吏덈웾遺꾩꽍湲곕 씠슜븳 Succinylacetone 痢≪젙 諛 뙋젙湲곗移 궛젙
Measurement of Succinylacetone Using HPLC-Tandem Mass Spectrometry and Establishment of a Cut-off Value
J Lab Med Qual Assur 2018;40:149-154
Published online September 30, 2018
© 2018 Korean Association of External Quality Assessment Service.

쟾꽑씗1,*, 꽌醫낅룄2,*, 씠寃쏀썕1,2, 넚젙븳1,2
Sun Hee Jun1,*, Jong Do Seo2,*, Kyunghoon Lee1,2, Junghan Song1,2

1遺꾨떦꽌슱븰援먮퀝썝 吏꾨떒寃궗쓽븰怨,
2꽌슱븰援 쓽怨쇰븰 寃궗쓽븰援먯떎

1Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
2Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
Correspondence to: Junghan Song Department of Laboratory Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7691 Fax: +82-31-787-4015 E-mail: Songjhcp@snu.ac.kr
援먯떊옄: 넚젙븳 슦)13620 寃쎄린룄 꽦궓떆 遺꾨떦援 援щ몃줈 173踰덇만 82, 遺꾨떦꽌슱븰援먮퀝썝 吏꾨떒寃궗쓽븰怨 Tel: 031)787-7691, Fax: 031)787-4015, E-mail: songjhcp@snu.ac.kr
Received April 11, 2018; Revised July 9, 2018; Accepted July 9, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

諛곌꼍:

씠濡쒖떊삁利 以 씠濡쒖떊쓽 利앷媛 떖븯吏 븡 씪떆쟻 떊깮븘 씠濡쒖떊삁利앷낵 젣1삎 씠濡쒖떊삁利앹 씠濡쒖떊 냽룄留뚯쑝濡쒕뒗 媛먮퀎씠 뼱젮썙 異붽쟻쑝濡 succinylacetone 利앷 쑀臾대 솗씤븯뿬빞 븳떎. 蹂 뿰援ъ뿉꽌뒗 嫄댁“삁븸諛섏젏(dried blood spot, DBS)뿉꽌 HPLC-깲뜡吏덈웾遺꾩꽍湲(HPLC-MS/MS)瑜 씠슜븯뿬 succinylacetone쓣 痢≪젙븯怨 씠뿉 븳 뙋젙湲곗移섎 궛젙븯떎.

諛⑸쾿:

DBS뿉꽌 異붿텧븳 succinylacetone hydrazine쑝濡 쑀룄泥대 留뚮뱺 썑 HPLC-MS/MS瑜 씠슜븯뿬 痢≪젙븯떎. Succinylacetone怨 궡遺몴以臾쇱쭏쓽 multiple reaction monitoring transition (m/z)쑝濡 155.1넂137怨 160.1넂142쓣 媛곴컖 궗슜븯떎. 떊깮븘꽑蹂꾧궗뿉꽌 젙긽쓽 寃곌낵瑜 蹂댁뜕 127媛쒖쓽 DBS 씠濡쒖떊씠 넂븯뜕 93媛 DBS뿉꽌 succinylacetone쓣 痢≪젙븯怨, 洹 寃곌낵瑜 씠슜븯뿬 뙋젙湲곗移섎 궛젙븯떎.

寃곌낵:

떊깮븘꽑蹂꾧궗뿉꽌 젙긽쓽 寃곌낵瑜 蹂댁씤 127媛 DBS쓽 succinylacetone 寃곌낵뒗 룊洹 0.34 쨉mol/L (0-1.28 쨉mol/L)쓽 寃곌낵遺꾪룷瑜 蹂댁떎. 삉븳 씠濡쒖떊 냽룄媛 젙긽蹂대떎 넂븯뜕 93媛 DBS쓽 succinylacetone 寃곌낵뒗 룊洹 0.77 쨉mol/L (0.16-1.70 쨉mol/L)쓽 寃곌낵遺꾪룷瑜 蹂댁뿬 젙긽 떊깮븘蹂대떎 넻怨꾩쟻쑝濡 쑀쓽븯寃 넂 寃곌낵遺꾪룷瑜 蹂댁떎(T寃젙, P<0.001). 127紐낆쓽 젙긽 DBS瑜 긽쑝濡 궛젙븳 以묒븰媛+5 standard deviation (SD) 뙋젙湲곗移섎뒗 1.4 쨉mol/L씠뿀怨, 씠濡쒖떊씠 利앷릺뼱 엳吏留 TNT媛 쓽떖릺뒗 93紐낆쓣 룷븿븯뿬 珥 220紐낆쓣 긽쑝濡 궛젙븳 以묒븰媛+5SD 뙋젙湲곗移섎뒗 2.1 쨉mol/L떎.

寃곕줎:

DBS succinylacetone뿉 븳 쟻젅븳 뙋蹂꾧린以移섎 궛젙븯뿬 씠슜븳떎硫, 떊깮븘꽑蹂꾧궗뿉꽌 씠濡쒖떊 냽룄媛 젙긽蹂대떎 넂 寃쎌슦 succinylacetone쓽 痢≪젙 씠濡쒖떊삁利 議곌린媛먮퀎吏꾨떒뿉 빐 쑀슜븷 寃껋쑝濡 깮媛곷맂떎.

Background:

Newborn screening of tyrosinemia type 1 is important for identifying infants at risk for developing this disease before life-threatening symptoms occur. It is difficult to differentiate between tyrosinemia type 1 and transient neonatal tyrosinemia (TNT) by analyzing tyrosine alone. Thus, succinylacetone must be analyzed. In this study, we measured succinylacetone in dried blood spot (DBS) by HPLC-tandem mass spectrometry (HPLC-MS/MS) and established cut-off values.

Methods:

We used the hydrazine derivatization method to measure succinylacetone in 127 DBSs showing normal results in the newborn screening test and 93 DBSs showing increased tyrosine levels. We established cut-off values using the 99.9th percentile value or median+5 standard deviation value.

Results:

Succinylacetone levels determined by our method were well-correlated with the results recommended by the Centers for Disease Control and Prevention for proficiency testing (r=0.9968). The succinylacetone levels in normal newborn DBSs were significantly lower than those in DBSs with high tyrosine levels (P<0.001). The cut-off values were calculated to be 1.3 00000000M from the results of 127 normal DBS samples and 2.2 關M from 220 DBSs, including in 93 newborns with TNT.

Conclusions:

Measurement of succinylacetone in DBSs by HPLC-MS/MS is useful in individuals with increased tyrosine concentrations and can be used for rapid differential diagnosis of tyrosinemia when an appropriate cut-off value is established.

Keywords : Succinylacetone, Tyrosinemias, Tandem mass spectrometry
꽌 濡

씠濡쒖떊삁利(tyrosinemia) 씠濡쒖떊 궗뿉 愿뿬븯뒗 슚냼쓽 寃고븤뿉 쓽빐 삁以 씠濡쒖떊 냽룄媛 젙긽蹂대떎 넂븘吏뒗 쑀쟾꽦궗吏덊솚쑝濡 씪떆쟻 떊깮븘 씠濡쒖떊삁利(transient neonatal tyrosinemia, TNT)怨 젣1삎 씠濡쒖떊삁利(tyrosinemia type 1), 젣2삎 씠濡쒖떊삁利(tyrosinemia type 2), 젣3삎 씠濡쒖떊삁利(tyrosinemia type 3) 벑 뿬윭 醫낅쪟媛 엳떎[1,2]. 씠 以 젣2怨 젣3삎 씠濡쒖떊삁利앹 tyrosine aminotransferase怨 4-hydroxyphenylpyruvate dioxygenase (HPD)媛 媛곴컖 寃고븤릺뼱 씠濡쒖떊쓽 떖븳 利앷瑜 蹂댁씠湲 븣臾몄뿉 돺寃 媛먮퀎씠 媛뒫븯떎[1,2]. TNT쓽 寃쎌슦 떊깮븘쓽 HPD 슚냼媛 誘몄꽦닕븯뿬 씠濡쒖떊 궗냽룄媛 뒭뼱吏硫댁꽌 씠濡쒖떊 냽룄媛 씪떆쟻쑝濡 넂븘吏뒗 寃쎌슦씤뜲, 씠븣 씠濡쒖떊 利앷 젙룄뒗 떖븯吏 븡怨 洹 利앷룄 씪떆쟻쑝濡 굹굹誘濡 蹂꾨룄쓽 移섎즺媛 븘슂븯吏 븡떎. 洹몃윭굹 젣1삎 씠濡쒖떊삁利앹 씠濡쒖떊 궗뿉 愿뿬븯뒗 fumarylacetoacetate hydrolase 슚냼媛 寃고븤씠 릺뼱 fumaric acetoacetic acid媛 fumaric acid acetoacetate濡 遺꾪빐릺吏 紐삵븯怨 泥대궡뿉 씠濡쒖떊怨 succinylacetone쑝濡 異뺤쟻릺뼱 媛꾧낵 떊옣쓽 넀긽怨 떊寃쎌쭏솚씠굹 씤궛꽦援щ(蹂 벑쓽 吏덊솚쓣 씪쑝궓떎[1-3]. 젣1삎 씠濡쒖떊삁利앹 100,000紐낅떦 1紐낃섦濡 諛쒕퀝븯뒗 留ㅼ슦 뱶臾 吏덊솚쑝濡 議곌린뿉 移섎즺 븯吏 紐삵븯硫 1꽭 씠븯뿉 궗留앺븯뒗 떖媛곹븳 꽑泥쒖꽦 궗吏덊솚씠吏留 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione濡 移섎즺媛 媛뒫븯怨 떊깮븘떆湲곗뿉 移섎즺瑜 떆옉븯寃 릺硫 뜑슧뜑 슚怨쇱쟻씠씪뒗 蹂닿퀬룄 엳뼱 씠濡쒖떊삁利앹뿉꽌 씠 吏덈퀝쓽 議곌린 媛먮퀎 留ㅼ슦 以묒슂븯떎[2,4,5]. 洹몃윭굹 씠濡쒖떊 利앷 젙룄媛 겕吏 븡湲 븣臾몄뿉 깲뜡吏덈웾遺꾩꽍湲(MS/MS)瑜 씠슜븳 떊깮븘꽑蹂꾧궗뿉꽌 TNT쓽 媛먮퀎씠 돺吏 븡떎. 뵲씪꽌 젣1삎 씠濡쒖떊삁利앹쓽 듅씠 吏몴옄씤 succinylacetone쓣 痢≪젙븯뿬 씠쓽 利앷뿬遺瑜 븿猿 솗씤븯뿬 媛먮퀎븯뿬빞 븳떎[2,6-9]. 뵲씪꽌 떊깮븘꽑蹂꾧궗뿉꽌 씠濡쒖떊씠 젙긽蹂대떎 넂寃 굹굹뒗 寃쎌슦, 떊깮븘뒗 떎떆 蹂묒썝뿉 궡썝븯뿬 蹂꾨룄쓽 냼蹂씠굹 삁븸쓣 梨꾩랬븯뿬 succinylacetone쓽 利앷 뿬遺瑜 솗씤븯湲 쐞븳 쑀湲곗궛寃궗 벑쓣 異붽濡 떆뻾븯떎[6,7]. 븯吏留 洹 寃궗寃곌낵瑜 솗씤븯湲곌퉴吏 2-3二쇱씪 젙룄 냼슂븯寃 릺뼱 議곌린媛먮퀎씠 돺吏 븡븯떎. 떊깮븘꽑蹂꾧궗 썑 씠濡쒖떊 냽룄媛 利앷븳 옍뿬 嫄댁“삁븸諛섏젏(dried blood spot, DBS)뿉꽌 succinylacetone쓣 吏곸젒 痢≪젙븯뒗 諛⑸쾿씠 媛쒕컻맂 썑濡쒕뒗 젣1삎 씠濡쒖떊삁利앹쓽 議곌린媛먮퀎吏꾨떒씠 媛뒫빐議뚯쑝硫, DBS瑜 씠슜븳 succinylacetone쓽 痢≪젙 湲곗〈쓽 諛⑸쾿怨 鍮꾧탳븷 븣 蹂꾨룄쓽 寃泥 梨꾩랬瑜 븘슂濡 븯吏 븡怨 鍮좊Ⅸ 寃곌낵솗씤씠 媛뒫븳 씠젏쓣 媛吏怨 엳뼱꽌 寃쎈룄 궡吏 以묐벑룄쓽 씠濡쒖떊 냽룄利앷瑜 蹂댁씠뒗 젣1삎 씠濡쒖떊삁利앷낵 TNT쓽 媛먮퀎吏꾨떒뿉 쑀슜븯寃 솢슜맆 닔 엳떎[2,8,9]. 洹몃윭굹 슦由щ굹씪 젙긽 떊깮븘 諛 TNT뿉꽌 씠濡쒖떊 냽룄뿉 뵲瑜 succinylacetone쓽 냽룄遺꾪룷뿉 븳 뿰援ш 吏꾪뻾맂 諛 뾾떎. 蹂 뿰援ъ뿉꽌뒗 젙긽 떊깮븘 TNT媛 쓽떖릺뒗 떊깮븘瑜 긽쑝濡 HPLC-MS/MS瑜 씠슜븯뿬 DBS뿉꽌 succinylacetone쓣 痢≪젙븿쑝濡쒖뜥 succinylacetone쓽 뙋젙湲곗移(cut-off value)瑜 궛젙븯怨, 씠濡쒖떊 냽룄뿉 뵲瑜 succinylacetone 遺꾪룷瑜 遺꾩꽍븯怨좎옄 븯떎.

옱猷 諛 諛⑸쾿

1. 寃泥

遺꾨떦꽌슱븰援먮퀝썝뿉꽌 異쒖깮 떆 泥댁쨷 諛 엫떊二쇱닔媛 젙긽씤 떊깮븘瑜 긽쑝濡 깮썑 3-5씪 궗씠뿉 떆뻾븳 떊깮븘꽑蹂꾧궗뿉꽌 씠濡쒖떊씠 250 關mol/L 誘몃쭔쑝濡 젙긽寃곌낵瑜 蹂댁뜕 DBS 옍뿬寃泥대 議곌뎔쑝濡 닔吏묓븯떎. TNT 솚옄援곗 2009뀈 8썡遺꽣 2012뀈 4썡源뚯 떆뻾븳 떊깮븘꽑蹂꾧궗뿉꽌 씠濡쒖떊씠 250 關mol/L 씠긽쑝濡 鍮꾩젙긽냼寃ъ쓣 蹂댁씠怨 엫긽쟻 利앹긽씠 뾾쑝硫댁꽌 異붿쟻寃궗뿉꽌 씠濡쒖떊씠 젙긽솕릺뿀뜕 93媛쒖쓽 DBS 옍뿬寃泥대 긽쑝濡 닔吏묓븯떎.

2. 떆빟

Succinylacetone, hydrazine monohydrate, formic acid, acetonitrile, ethanol, 利앸쪟닔 벑 HPLC 벑湲됱쑝濡 Sigma-Aldrich (St. Louis, MO, USA) J.T. Baker (Avantor Performance Materials; Center Valley, PA, USA)뿉꽌 援щℓ븯뿬 궗슜븯떎. 궡遺몴以臾쇱쭏(internal standard, IS) 13C5-succinylacetone (Cambridge Isotope Laboratories Inc., Tewksbury, MA, USA)쓽 젣뭹쓣 궗슜븯떎.

3. Succinylacetone 痢≪젙

Succinylacetone 蹂댁젙臾쇱쭏怨 젙룄愿由щЪ吏덉 떆뙋릺뒗 臾쇱쭏씠 뾾뼱 옄媛 젣議고븯뿬 궗슜븯떎. 蹂댁젙臾쇱쭏 쟾삁뿉 succinylacetone쓣 0, 0.63, 1.58, 3.16, 4.74, 6.32 關mol/L媛 릺룄濡 泥④븯뿬 옒 샎빀븳 썑, 뿬怨쇱(Whatman No 901; GE Healthcare Bioscience, Pittsburgh, PA, USA)뿉 100 關L뵫 遺꾩<븯뿬 DBS瑜 留뚮뱾뼱 긽삩, 븫떎뿉꽌 異⑸텇엳 留먮┛ 썑 -70째C쓽 깋룞怨좎뿉 蹂닿븯뿬 궗슜븯떎. 젙룄愿由щЪ吏덉 젙긽 떊깮븘 寃泥대줈 젣議고븳 DBS 젙긽 寃泥댁뿉 1.90 關mol/L succinylacetone쓣 泥④븯뿬 怨좊냽룄濡 젣議고븳 DBS瑜 媛곴컖 냽룄 怨좊냽룄 젙룄愿由щЪ吏덈줈 궗슜븯떎. IS뒗 80% acetonitrile濡 0.13 關mol/L 냽룄媛 릺寃 젣議고븯뿬 궗슜븯떎.

蹂댁젙臾쇱쭏, 젙룄愿由щЪ吏 諛 떊깮븘 DBS 寃泥댁뿉꽌 媛곴컖 3/16씤移 뵒뒪겕瑜 梨꾩랬븯뿬 96-well plate뿉 삷寃쇰떎. IS 슜븸 100 關L瑜 媛 well뿉 꽔怨 援먮컲湲곗뿉꽌 5遺꾧컙 옒 샎빀븯떎. 200 mmol/L쓽 hydrazine monohydrate 1.5 關L瑜 떎떆 媛 well뿉 꽔뼱以 썑 떎떆 5遺꾧컙 異⑸텇엳 샎빀븯떎. 利앸컻쓣 留됯린 쐞빐 plate뿉 뜮媛 븘由꾩쓣 遺李⑺븳 썑 60째C뿉꽌 30遺꾧컙 succinylacetone쓽 쑀룄泥닿 삎꽦릺룄濡 븯떎. 쑀룄솕媛 걹궃 슜異쒖븸 90 關L瑜 떎瑜 96-well plate뿉 삷湲 썑 吏덉냼媛뒪븯뿉꽌 빟 10遺꾧컙 셿쟾엳 嫄댁“븯떎. 궓븘 엳뒗 hydrazine쓣 셿쟾엳 뾾븷湲 쐞븯뿬 100 關L쓽 ethanol쓣 媛 well뿉 꽔怨 떎떆 吏덉냼媛뒪븯뿉꽌 셿쟾엳 嫄댁“븯떎. 씠 嫄댁“맂 寃泥대 60 關L쓽 80% acetonitrile 슜븸쑝濡 옱遺쑀븳 썑 HPLC-MS/MS쓽 옄룞 寃泥 二쇱엯援ъ뿉 옣李⑺븯뿬 寃궗瑜 吏꾪뻾븯떎.

HPLC뒗 AQUITY UPLC system (Waters, Watford, UK)뿉 BEH C18 而щ읆(2.1횞50 mm, 1.7 關m; Waters)쓣 궗슜븯怨, 쑀냽 0.2 mL/min, 遺꾩꽍떆媛 3遺, 씠룞긽 A뒗 0.1% formic acid 瑜 룷븿븳 acetonitrile, 씠룞긽 B뒗 0.1% formic acid瑜 룷븿븳 利앸쪟닔瑜 궗슜븯뿬 A B瑜 8:2쓽 鍮꾩쑉濡 벑슜留ㅻ줈 吏꾪뻾븯떎. Succinylactone 뵾겕뒗 젙泥댁떆媛 0.65 (0.60-0.70)遺꾩뿉꽌 愿李곕릺뿀떎. 吏덈웾遺꾩꽍湲곕뒗 Xevo TQ MS (Waters)瑜 궗슜븯怨 쟾湲곕텇궗씠삩솕(electrospray ionization), 뼇씠삩 紐⑤뱶, multiple reaction monitoring (MRM) 議곌굔뿉꽌 寃궗瑜 떆뻾븯떎. Succinylacetone怨 IS쓽 MRM transition (m/z) 155.1넂137怨 160.1넂142瑜 媛곴컖 씠슜븯떎. Cone voltage collision energy뒗 媛곴컖 22 V 10 eV濡 븯떎. 痢≪젙맂 옄猷뚯쓽 젙웾 QuanLynx 4.0 (Waters) 냼봽듃썾뼱 봽濡쒓렇옩쓣 씠슜븯떎. 젙룄愿由щЪ吏덉뿉 븯뿬 10쉶 諛섎났痢≪젙쓣 떆뻾븯뿬 솗씤븳 寃궗 궡 젙諛룄뒗 怨좊냽룄 냽룄 젙룄愿由щЪ吏덉뿉 븯뿬 媛곴컖 6.3%, 13.6%怨, 11씪媛꾩쓽 寃궗 媛 젙諛룄뒗 怨좊냽룄 냽룄 젙룄愿由щЪ吏덉뿉 븯뿬 媛곴컖 11.0%, 13.3%떎. 吏곸꽑꽦 룊媛뿉꽌뒗 0-6.32 關mol/L 냽룄踰붿쐞뿉꽌 湲곗슱湲곕뒗 1.0372, 젅렪 -0.1134, R2=0.9979濡, succinylacetone 痢≪젙뿉 떊猶고븷 留뚰븳 寃곌낵瑜 蹂댁뿬 二쇱뿀떎.

4. 誘멸뎅 Centers for Disease Control and Prevention 젙룄愿由щЪ吏덇낵쓽 긽愿꽦 룊媛

쁽옱 succinylacetone 젙룄愿由 DBS媛 蹂꾨룄濡 떆뙋릺吏 븡怨 긽愿꽦쓣 룊媛븷 鍮꾧탳諛⑸쾿룄 뾾뼱, 誘멸뎅 Centers for Disease Control and Prevention (CDC)뿉꽌 2011뀈룄뿉 吏꾪뻾븳 succinylacetone 젙룄愿由 DBS 寃泥 4醫낅쪟(lot 25, 26, 27, 28)瑜 씠슜븯뿬 蹂 뿰援ъ뿉꽌 媛쒕컻븳 諛⑸쾿쑝濡 媛곴컖쓽 寃泥댁뿉 븯뿬 3쉶 諛섎났痢≪젙쓣 떆뻾븳 썑 洹 룊洹좉컪怨 CDC뿉꽌 沅뚯옣븳 寃곌낵踰붿쐞 諛 李몄뿬湲곌쓽 룊洹좉컪怨 鍮꾧탳븯쑝硫, Deming Regression 遺꾩꽍쓣 떎떆븯떎.

5. 뙋젙湲곗移 궛젙

DBS succinylacetone 뙋젙湲곗移섎뒗 젙긽 떊깮븘 127紐낃낵, TNT媛 쓽떖릺뒗 93紐낆쓣 룷븿븳 220紐 쟾泥대 긽쑝濡 媛곴컖 99.9띁꽱씪 媛믨낵 以묒븰媛+5 standard deviation (SD) 媛믪쑝濡 궛젙븯떎.

6. 넻怨꾩쿂由

넻怨꾨텇꽍 Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA), MedCalc ver. 14.12.0 (MedCalc Software BVBA, Ostend, Belgium), CBstat5 ver. 5.1.2 (Kristian Linnet, Charlottenlund, Denmark) 봽濡쒓렇옩쓣 궗슜븯떎.

寃 怨

2011뀈룄뿉 誘멸뎅 CDC뿉꽌 吏꾪뻾븳 succinylacetone 젙룄愿由 DBS 4醫낅쪟(lot 25, 26, 27, 28)뿉 븯뿬 3쉶 諛섎났寃궗瑜 떆뻾븯떎(Table 1). 냽룄씤 lot 25뿉꽌뒗 沅뚯옣踰붿쐞蹂대떎 빟媛 넂 寃곌낵瑜, 怨좊냽룄뿉꽌뒗 쟾諛섏쟻쑝濡 빟媛 궙 寃곌낵瑜 蹂댁떎. Deming Regression 遺꾩꽍뿉꽌 湲곗슱湲곕뒗 0.8661 (95% confidence interval [CI], 0.5029 to 1.2293), 젅렪 0.0970 (95% CI, 0.9794 to 1.1734)怨, 긽愿怨꾩닔뒗 0.9965濡 뼇샇븳 긽愿愿怨꾨 굹궡뿀떎.

Table 1 . Comparison of succinylacetone levels determined in the present study, CDC recommended values, and averages of participating laboratories in 2011 CDC proficiency testing for succinylacetone using dried blood spots.

Survey material lotsResults of this study (關mol/L)CDC recommended ranges (關mol/L) (mean)Averages of participating labs (關mol/L) (no. of participants)
250.150.100.14 (0.12)0.66 (231)
262.322.373.34 (2.84)2.54 (230)
274.934.345.81 (5.05)4.37 (237)
288.958.7511.21 (10.42)8.30 (239)

Abbreviation: CDC, centers for disease control and prevention..


떊깮븘꽑蹂꾧궗뿉꽌 씠濡쒖떊 냽룄媛 젙긽寃곌낵瑜 蹂댁씤 127媛 DBS쓽 succinylacetone 寃곌낵뒗 룊洹 0.34 關mol/L, 몴以렪李 0.22 關mol/L, 0-1.28 關mol/L쓽 寃곌낵遺꾪룷瑜 蹂댁쑝硫, 以묒븰媛믪 0.31 關mol/L, 궗遺꾩쐞닔 援ш컙 0.18-0.42 關mol/L떎. 삉븳 씠濡쒖떊 냽룄媛 젙긽蹂대떎 넂븯뜕 93媛 DBS쓽 succinylacetone 寃곌낵뒗 룊洹 0.77 關mol/L, 몴以렪李 0.31 關mol/L, 0.16-1.70 關mol/L쓽 寃곌낵遺꾪룷瑜 蹂댁쑝硫, 以묒븰媛믪 0.77 關mol/L, 궗遺꾩쐞닔 援ш컙 0.56-0.96 關mol/L濡, 젙긽 떊깮븘 DBS쓽 succinylacetone蹂대떎 넻怨꾩쟻쑝濡 쑀쓽븯寃 넂 寃곌낵遺꾪룷瑜 蹂댁떎(T寃젙, P<0.001) (Fig. 1). 珥 220媛 DBS쓽 succinylacetone 寃곌낵뒗 룊洹 0.52 關mol/L, 몴以렪李 0.34 關mol/L, 0-1.70 關mol/L쓽 寃곌낵遺꾪룷瑜 蹂댁쑝硫, 以묒븰媛믪 0.45 關mol/L, 궗遺꾩쐞닔 援ш컙 0.25-0.76 關mol/L떎.

Figure 1.

Distribution of succinylacetone levels and median+5 standard deviation cut-off values in dried blood spot from normal newborns (n=127) and the newborns with suspected neonatal transient tyrosinemia (TNT) (n=93).


127媛쒖쓽 젙긽 DBS쓽 succinylacetone 냽룄瑜 긽쑝濡 99.9띁꽱씪 媛믨낵 以묒븰媛+5SD 媛믪쑝濡 궛젙븳 뙋젙 湲곗移섎뒗 媛곴컖 1.3 關mol/L 1.4 關mol/L떎. 씠濡쒖떊씠 利앷릺뼱 엳吏留 TNT媛 쓽떖릺뒗 93紐낆쓣 룷븿븯뿬 珥 220紐낆쓣 긽쑝濡 99.9띁꽱씪 媛믨낵 以묒븰媛+5SD 媛믪쑝濡 궛젙븳 뙋젙湲곗移섎뒗 媛곴컖 1.7 關mol/L 2.1 關mol/L떎.

怨 李

蹂 뿰援ъ뿉꽌 媛쒕컻븳 諛⑸쾿쑝濡 2011뀈 CDC 젙룄愿由 DBS쓽 succinylacetone쓣 痢≪젙븳 寃곌낵瑜 궡렣蹂대㈃ lot 25뒗 0.15 關mol/L怨 젙룄愿由ы봽濡쒓렇옩뿉 李몄뿬븯뜕 231湲곌뱾쓽 룊洹좉껐怨쇰뒗 0.66 關mol/L떎. CDC뿉꽌뒗 沅뚯옣븯뒗 踰붿쐞뒗 0.10-0.14 關mol/L떎. Lot 28 寃곌낵뒗 8.95 關mol/L怨 젙룄愿由ы봽濡쒓렇옩 李멸湲곌쓽 룊洹좎 8.30 關mol/L, CDC뿉꽌뒗 沅뚯옣븯뒗 踰붿쐞뒗 8.75-11.21 關mol/L떎. 蹂 뿰援ъ뿉꽌 媛쒕컻븳 寃궗諛⑸쾿씠 떎瑜 李멸린湲곌蹂대떎 CDC뿉꽌 沅뚯옣븳 寃곌낵踰붿쐞뿉 뜑 洹쇱젒븯怨 엳뒗 寃껋쓣 븣 닔 엳떎. 씠뒗 遺遺꾩쓽 떎瑜 湲곌뿉꽌 뒪겕由щ떇 紐⑹쟻쑝濡 궗슜븯湲 쐞빐 蹂댁젙臾쇱쭏냽룄瑜 븳 媛吏留 궗슜븯뿬 젙웾븳 諛섎㈃, 蹂 뿰援ъ뿉꽌뒗 0뿉꽌 6.32 關mol/L源뚯 6떒怨꾩쓽 蹂댁젙臾쇱쭏쓣 궗슜븯湲 븣臾몄뿉 醫 뜑 젙솗븳 寃껋쑝濡 뙋떒맂떎.

씠濡쒖떊씠 넂븯뜕 93紐낆쓽 떊깮븘 DBS뒗 紐⑤몢 TNT씤 寃쎌슦濡 엫긽쟻 異붿쟻 諛 떊깮븘꽑蹂꾧궗 떦떆 룞씪븳 吏덈웾遺꾩꽍踰 異붿쟻寃궗瑜 넻븯뿬 씠濡쒖떊쓽 젙긽솕瑜 愿李고븿쑝濡쒖뜥 솗씤릺뿀쑝硫, TNT 솚옄뿉꽌 succinylacetone 닔移섍 127紐낆쓽 젙긽 DBS蹂대떎 넻怨꾩쟻쑝濡 쓽誘 엳寃 넂 寃곌낵瑜 蹂댁씤떎뒗 깉濡쒖슫 궗떎쓣 븣寃 릺뼱 succinylacetone 냽룄瑜 諛뷀깢쑝濡 TNT瑜 媛먮퀎 吏꾨떒븯뒗 寃껋뿉 룄씠 맆 寃껋쑝濡 뙋떒릺뿀떎.

엫긽寃궗쓽 李멸퀬移섎 궛젙븯뒗 諛⑸쾿 뿬윭 媛吏媛 엳쑝굹 Clinical & Laboratory Standards Institute (CLSI)뿉꽌 젣떆븯뒗 諛⑸쾿씠 蹂댄렪쟻쑝濡 궗슜릺怨 엳떎[10]. 젙긽 吏묐떒뿉꽌쓽 痢≪젙븳 媛믪씠 젙洹쒕텇룷瑜 븯뒗 寃쎌슦뿉뒗 2SD +2SD瑜 李멸퀬踰붿쐞濡 궛젙븯怨, 젙洹쒕텇룷瑜 븯吏 븡뒗 寃쎌슦뿉뒗 2.5띁꽱씪怨 97.5띁꽱씪 媛믪쓣 李멸퀬踰붿쐞濡 궛젙븯룄濡 沅뚭퀬븯怨 엳떎. 洹몃윭굹 쑀쟾꽦궗吏덊솚 遺遺 씗洹吏덊솚씠湲 븣臾몄뿉 씠 吏덊솚뿉 븳 떊깮븘 꽑蹂꾧궗쓽 李멸퀬移섎 CLSI 諛⑸쾿쑝濡 꽕젙븷 寃쎌슦 꼫臾 留롮 쐞뼇꽦瑜좎씠 깮湲곕뒗 臾몄젣젏씠 엳떎. 깲뜡吏덈웾遺꾩꽍湲곕 씠슜븳 쑀쟾꽦궗吏덊솚뿉 븳 꽑蹂꾧궗쓽 뙋젙湲곗移섎 궛젙븯뒗 媛옣 醫뗭 諛⑸쾿쑝濡쒕뒗 솗吏꾨맂 솚옄瑜 긽쑝濡 痢≪젙븳 寃곌낵媛 엳쓣 寃쎌슦 젙긽씤怨 솚옄瑜 솗뿰엳 遺꾨퀎븯뒗 媛믪쓣 뙋젙湲곗移섎 궛젙븯뒗 寃껋씠떎. 洹몃윭굹 遺遺꾩쓽 쑀쟾꽦궗吏덊솚쓽 寃쎌슦 솗吏꾨맂 솚옄 寃泥대 援ы븯뒗 寃껋씠 뼱졄湲 븣臾몄뿉 젙긽씤쓣 긽쑝濡 痢≪젙븳 媛믪뿉꽌 99.9띁꽱씪 삉뒗 以묒븰媛+5SD 媛믪쓣 궗슜븯湲곕룄 븳떎. La Marca 벑[8] 以묒븰媛+5SD 媛믪쑝濡 궛젙븯뿬 2.4 關mol/L 媛믪쓣 젣떆븯怨, Metz 벑[9] 99.9띁꽱씪 媛믪쑝濡 궛젙븯뿬 1.29 關mol/L 媛믪쓣 젣떆븯떎. 理쒓렐쓽 醫낆꽕뿉 쓽븯硫 蹂닿퀬옄뿉 뵲씪 1.29遺꽣 10 關mol/L源뚯 떎뼇븳 뙋젙湲곗移섎 궗슜븯怨 엳怨[11], 떊鍮숇룄議곗궗寃곌낵룄 諛⑸쾿 媛꾩뿉 李⑥씠瑜 蹂댁씠怨 엳뒗뜲, 씠뒗 諛⑸쾿 媛꾩쓽 DBS 異붿텧踰뺤쓽 李⑥씠, IS쓽 李⑥씠, 蹂댁젙諛⑸쾿쓽 李⑥씠 븣臾몄뿉 湲곗씤븳 寃껋쑝濡 異붿젙븯떎. 뵲씪꽌 媛 寃궗떎留덈떎 옄泥 뙋젙湲곗移 媛믪쓣 꽕젙븯嫄곕굹 寃利앺븯뒗 寃껋씠 븘슂븯떎.

蹂 뿰援ъ뿉꽌 젙긽 떊깮븘瑜 긽쑝濡 以묒븰媛+5SD쓣 湲곗쑝濡 뙋젙湲곗移섎 궛젙븳 媛믪 1.4 關mol/L떎. 씠 뙋젙湲곗移섎 궗슜븷 寃쎌슦 TNT濡 쓽떖릺뒗 떊깮븘쓽 3.2% (3/93紐)뿉꽌 쐞뼇꽦쓣 蹂댁떎. 뵲씪꽌 씠濡쒖떊씠 250 關mol/L 씠긽 利앷릺뼱 TNT媛 쓽떖릺뒗 寃쎌슦 TNT瑜 룷븿떆耳 궛젙븳 뙋젙湲곗移섏씤 2.1 關mol/L瑜 궗슜븯뒗 寃껋씠 諛붾엺吏곹븷 寃껋쑝濡 뙋떒릺硫, 씠뒗 1.29 關mol/L쓽 뙋젙湲곗移섎 젣븞븯뜕 Metz 벑[9]쓽 뿰援щ 젣쇅븯硫, 醫낆꽕뿉꽌 뙆븙맂 2.0遺꽣 10 關mol/L 踰붿쐞쓽 媛쒕퀎뿰援 뙋젙湲곗移섏룄 遺빀븯硫 媛곴컖쓽 뿰援ъ뿉꽌 넂 誘쇨컧룄 듅씠룄, 뼇꽦삁痢〓룄瑜 蹂댁떎[11].

蹂 뿰援ъ쓽 젣븳젏 뙋젙湲곗移 궛젙쓣 쐞븳 긽닔媛 쟻뿀怨, 젣1삎 씠濡쒖떊삁利 솚옄濡 吏꾨떒諛쏆 DBS 寃泥닿 뾾뼱 궛젙맂 뙋젙湲곗移섏뿉 븳 쐞뼇꽦, 쐞쓬꽦瑜 벑 젙솗룄 룊媛瑜 옄泥댁쟻쑝濡 떆뻾븯吏 紐삵븯怨, 湲곗〈뿉 蹂닿퀬맂 臾명뿄怨쇱쓽 鍮꾧탳留뚯쓣 떆뻾븳 寃껋씠떎. 븵쑝濡 떊깮븘꽑蹂꾧궗媛 쓽猶곕맂 DBS뿉꽌 succinylacetone 痢≪젙쓣 怨꾩냽 떆뻾븯뿬 젙긽援 諛 鍮 젙긽援곗쓽 寃곌낵瑜 뒛젮굹媛 寃곌낵異붿씠瑜 궡렣蹂대뒗 寃껋씠 븘슂븯떎.

떊깮븘 꽑蹂꾧궗뿉꽌 씠濡쒖떊 냽룄媛 젙긽蹂대떎 利앷븯뒗 寃쎌슦, 蹂꾨룄쓽 寃泥 梨꾩랬 뾾씠 옍뿬 DBS 寃泥댁뿉꽌 succinylacetone 痢≪젙쓣 떆뻾븿쑝濡쒖뜥 씠濡쒖떊삁利앹쓽 遺遺꾩쓣 李⑥븯뒗 TNT 젣1삎 씠濡쒖떊삁利앹쓽 議곌린媛먮퀎씠 媛뒫븯寃 릺뿀떎. 씠뒗 뿬윭 媛吏 寃쎌젣쟻 鍮꾩슜肉먮쭔 븘땲씪 寃곌낵瑜 諛쏄린源뚯 蹂댄샇옄뱾씠 諛쏅뒗 뒪듃젅뒪굹 嫄깆젙 벑쓣 留롮씠 빐냼븯寃 맆 寃껋씠떎.

젣1삎 씠濡쒖떊삁利앹쓣 議곌린媛먮퀎吏꾨떒븯뿬 移섎즺瑜 떆옉븯寃 릺硫 90%쓽 솚옄媛 蹂꾨떎瑜 利앹긽 뾾씠 슚怨쇱쟻쑝濡 移섎즺媛 媛뒫븯떎. 뵲씪꽌 succinylacetone 寃궗瑜 湲곗〈쓽 깲뜡吏덈웾遺꾩꽍湲곕 씠슜븳 떊깮븘꽑蹂꾧궗 븿猿 떆뻾븯怨 쟻젅븳 뙋蹂꾧린以移섎 궗슜븳떎硫 젣1삎 씠濡쒖떊삁利앹쓽 議곌린媛먮퀎吏꾨떒뿉 쑀슜븷 寃껋쑝濡 깮媛곷맂떎.

媛먯궗쓽 湲

蹂 뿰援щ뒗 遺꾨떦꽌슱븰援먮퀝썝 씪諛섏뿰援щ퉬(02-2010-005) 吏썝뿉 쓽빐 씠猷⑥뼱議뚮떎.

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