Tap chi GAN MAT VIET NAM s6 29-2014 33
cr dpng sac t6 s3t or tre sor sinh mpt nguyen nhan gay suy gan sdm o"
tre Sff sinh
Report 3 infants in a family affected by Neonatal Hemochromatosis
Nguyen Ph^m Anh Hoa'. Nguyen Gia Khdnh^. Le To Nhu', Hodng Ngoc Thach', Khu Thi Khdnh Dung', Nguyin Thanh Hucmg', B6 Thi Hdi', Nguyin Thi Thia', Peter Whitington^
Tdm tat: XS dpng sac to s§t a tre sa sinh ( Neonatal Hemochromatosis-NH) la benh hiim gap, Uen quan toi su u sit trong gan va cac tang ngoai gan, la mot trong nhung nguyen nhan gay suy gan som va nang a tre so sinh. Ca chS gay b^nh NH hien con chua ro rang. Tuy co tien lugng nang song cac tre NH co the dugc cuu song neu dugc chan doan va dieu tri sam. 6 cac
ba me da co con bi NH, b$nh co the lap l^i a cac lan mang thai sau vai ty 1? rat cao. Trong nghien cuu nay, chung toi trinh bay 3 ca benh dugc chan doan NH trong ciing mot gia dinh, hai trong ba tre dugc dieu tri thanh cong bang cac thuoc dieu tri ho trg.
Tu khoa: neonatal hemochromatosis, suy gan s a s i n h
Abstract; Neonatal Hemochromatosis (NH) is a rare disease that has been clinically defined as severe neonatal liver failure disease in asso- ciation with liver and extrahepatic siderosis.The etiology of NH is not fully understood. How- ever, the high recurrence rate with fiiture preg- nancies. Although NH is severe and has poor
prognosis, early medical therapy treatment with antioxidant cocktail, exchange transfusion, liver transplantation...may be curartive. We report 3 infants in a family affected by NH, two of them are cured successfully by medical therapy
Key words: neonatal heamochromatosis, neonatal hepatic failure
1. Bg,t vdn de
B^nh ly Neonatal Hemochromatosis (NH) la m§t trong nhung nguydn nhan gay suy gan sam va n|ing a tre so sinh. B?nh rat hiem gap va c6 bieu hi?n lam sang da dang, lien quan tai su u dgng sit a nhidu tang nhu gan va cac tang khac.. .nhung khong lien quan toi benh roi loan chuySn hoa sit di truydn 6 nguai 1cm (Hereditary Haemochromatosis - HH). Ci cac ba me da co con bi NH, benh co thd lap lai a cac \in mang thai sau vcri ty 1? rit cao, co the tai tren 80%
[9,3]. B?nh nhan NH thudng vang da li mat, suy gan s6m va nang chi vai gia tcri vai ngay sau de [6]. Nguyen nhan gay b?nh NH toi nay chua ro rdng, nhieu gia thidt cho ring b?nh co the do cac yeu t6 ti^ midn dich lidn quan toi thai ky. Chan
doan NH can phoi hgp giua lam sang, tidn su gia dinh, xet nghidm (bidu hi$n cua suy te bao gan, roi loan dong man, tang feritin (> 800ng/ml), tang alpha fetoprotein (tren 80 OOOng/ml ndu tuoi thai>37 tuan, tren 200 OOOng/ml ndu tuoi thai<32 tuan), tang bao hoa transferin huydt thanh, transaminase tang hoac giam thap); chan doan hinh anh (li dgng sit bat thuang a gan va cac tang ngoai gan nhu tuy, lach, tim.. .trdn phim chup MRI), u dgng sat tren cac benh pham mo bdnh hpc cua gan, tuyen nuac bpt, lach, than, tim [6,2,9]. Tuy NH co tien lugng nang, nguy co tu vong cao song ndu dugc chan doan sam, bpnh nhan co the dugc cuu song nha phoi hgp cac phuang phap dieu trj tri?u chirng, thai sit, su dung cac chat chong oxy hoa, thay mau mpt 1. B?nh vi?n Nhi Trung ucmg. 2. Bp mon Nhi D^i hpc Y Ha Npi, 3. Children's Memonl Hospital Chicago, Illinois-America
34 Tap chi GAN MAT VIET NAM so 29-2014 phin, ghep gan... [2,3,4]. Me cua cac benh nhan NH dugc tu vin sii dung IVIG trong thai de han chd SIT anh huong ciia NH toi thai nhi [10,3].
Tai \^et Nam toi nay chua c6 bao cao nao ve NH. Trong nghien cuu nay, chiing toi trinh bay 3 bdnh nhan trong cung mot gia dinh dugc chan doan NH, trong do hai bdnh nhan dugc ciiu s6ng bang dieu tri npi khoa.
2. Bdo cdo ca benh
Ca b?nh 1: Bdnh nhan nii PHAN NG H. 1 thang tuoi, de thuong. Vao vidn do vang da li
mat, r6i loan dong mau sam ngay sau sinh. Tre la con thii 2, gia dinh co 1 con gai tu vong Iiic 18 ngay tuoi do vang da, suy gan khong ro nguydn nhan. B 6 me khoe manh, kh6ng ket hon can huydt, khong co tien su bdnh tat dac biet, me CO 1 lin thai luu. Tre vao vien trong tinh trang vang (ia li mat nang, xuat huydt tren da, chay mau noi tiem truyen. Gan lach to va chac, phu toan than, co chuong, tuan hoan bang he, phan vang, CO con xiu do ha duang huydt.
Xet nghiem can lam sang:
Xet nghiem Bilirubin TP (nmol/I) BilirulinTT(^mol/l) Bilirulin GT (|imol/l)
AST (U/L) ALT (U/L) Prothrombin %
Ket qua 806,8 465,2 341,6 1836,8 366 10%
Xet nshiem Fe (mmol/1) Feritin (mg/1)
AFP Protid (g/1) Albumin (g/1) Glucose (mmol/1)
Ket qua 38,1 7541 86 420
39,1 24,6 0,5
Xet nghiem LDH (U/L) hact£Lt (mmol/1)
Coombs test Elisa CMV, EBV
HCV, HBsAg NH3(mg/dl)
Ket qua 767,5
2,3 Am tinh Am tinh Am tinh 344 Kdt qua nhidm sac the: 46XXdell6 (q23)/46XX. Sieu am, CT 6 bung. CT so nao khong phat hidn cac bieu hien bat thuang.
Bdnh nhan dugc chan doan vang da li mat/
suy gan khong ro nguyen nhan. Tu vong liic 62 ngay tuoi. Mo hi thi thay gan teo, miin, ngim mat, CO nhidu didm tao mau ngoai tuy. Vi thd:
ton thuang thoai hoa td bao gan miic dp nang, li dgng Fe nhieu trong nhu mo gan, lach, tim. Chin doan xac dinh NH.
Ca benh 2: Benh nhan nam Phan Tr Th, vao vien liic 8 ngay tuoi do dupc tu van vd nguy co bi NH (tre c6 chi gai la benh nhan trong ca bdnh thii nhat). Tre vao vien trong tinh trang vang da sang, gan lach khong to, chiic nang gan bmh thucmg.
Xet nghiem Tuoi Lactat Fe Coombs test
LDH CMV, EBV HBsAg, HCV
8 ngdy 3,8mmol/l 28,lmmol/I Am tinh 350,5 U/L
Am tinh Am tinh
Xet nghiem
Bilirubin TP ((imol/l) Bilirulin TT(nmol/l) Bilirulin GT(^mol/l)
AST (U/L) ALT (U/L) Prothrombin %
8 ngdy 138,8 62,4 76,4 75,8 92,8 75
11 ngdy 256,4 112,5 114 484,5 688,4
<10
35 ngdy 215,9
98,7 117.2 375,5 534,8 96
Tap cU GAN MAT VIET NAM so 29-2014 35
Glucose (mmol/1) AFP
2,5 44 800
Protid (g/1) Albumin (g/1)
Feritin (ng/1) NH3 (mg/dl)
58,2 34,7 8670 186
48,4 22,6 6438 168
61,2 38,4 2480 85 Kdt qua nhiem sac thd bmh thucmg. Benh nhSn dugc chin doan xac dinh NH.
+ Didu tn trieu chiing: truyin plasma tuai, al- bilirubin, GGT.. .keo dai toi 12 thang tu6i (bika bumm, vitamm Kl; thudc chdng oxi hoa Vita- d6 1.1 va 1.2)
mm E (25UI/kg/ ngay), acetyl cystem -KTa b^nh 3 : Benh nhan nam Phan Q K, vao (lOOmg/kg/ngay); thai sit; truydn IVIG: sii vidn liic 1 ngay tu6i do tu vin co nguy co bi dung 3 lidu 1 g/kg; an sua Pregestimil benh Iy NH (tre la em cua hai b?nh nhan trong -I- Didn bidn: Chiic nang dong mau 6n dinh 2 ca benh 1 va 2). Kdt qua giai phau b?nh sau 3 tuan didu tri. Ra vi?n luc 35 ngay tuoi nhupm sat mo banh rau co hi?n tugng nhiem sat.
trong tinh tr^ng con vang da, gan lach to. Tinh Vao vien liic 1 ngay tuoi trong tinh tr^g tinh trang vang da, gan lach to, tang transminase, tao, vang da sang va nh?, gan lach khong to.
LDH (U/1) lactat mmol/1
Fe (mmoVl) Coombs test
AFP NH3 (mg/dl) Glucose (nmiol/1)
HCV, HBsAg PCR CMV, EBV
450,52 2,4 32,5 Am tinh 358 020 120 2,1 Am tinh Am tinh
Xet nghiem
Bilirubin TP (nmol/1) Bilirulin TT(nmol/l) Bilirulin GT(nmol/l)
AST (U/L) ALT (U/L) Prothrombin %
Protid (g/1) Albumin (g/1)
Feritin (ng/1)
1 ngay 80,2 32,5 47.7 120 165,4
35 48,6 24,5 4670
3 ngdy 115,5 48,4 83,1 84,5 66,2 84,6 58,6 32,8 3860
10 ngdy 62,9 28,5 34,3 56,8 42,7 88,2 56,8 34,8 1850 KSt qua nhilm sSc the binh thuong
B?nh nhan du(?c chan doan xAc dinh NH, diem 3 ngay tuoi song giam nhanh sau do. Chuc dilu trj theo phac do tai thoi dilm 2 ngay ta6i „5„g gan 6n dinh dSn ngay trong t u k dau sau bing plasma tucri, truyin albumin, tiem Vitamin ^^^ ^ 3 . ^ ^._^ ^^^ ^..^ ,^^ ,2 ngay tu&
Kl. Diing c6c thuoc Antioxidant: Vitamin
„ , , , A ., 1 * • khi het vang da, gan lach khong to. Cac xet (25Ul/kg/ngay), Acetyl cystem s . 6 6 (100mg*g/ngay).TmylnlliluIVlGlg*g.Tre nghi?m lam sang on dinh sau 1 thang dieu trj ( dip iJmg tdt voi dilu tri, vang da tang t?i thoi bieu do 1.1 va 1.2)
36 Tap ch! GAN MAT VitT NAM so 29-2014
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BI'IK tdi: Theo dot Bilirubin sau dilu trj Bieu do 2: Theo doi GOT, GPTsau dieu trj Theo doi: Hai benh nhan diu dugfc tiep tuc dieu tri ngoai tru va theo doi dinh ky Thu6c didu tri
Ursodeoxy cholic acid Vitamin E
Bdnh nhan 2
20mg/kg/ngdy x 6 thdng 25IU/kg/ngdy x 10 thdng
Bdnh nhan 3 20mg/kg/ngdy x Ithdng 25IU/kg/ ngdy x 2 thdng Hai bdnh nhan hien 4,5 va 2,5 tuoi, hoan toan khoe manh, phat trien tot ve the chat va tinh thin, chiic nang gan binh thuang.
3. Bdn lug.n
Du nguyen nhan gay bdnh NH chua thuc su ro rang, song thuc td cho thay a cac ba me da co con bi NH benh co kha nang lap lai rit cao a cac lan sinh sau [9,10]. Kho chan doan NH a nhiing truang hgp bdnh nhan la con diu, do da s6 cac benh nhan NH co r6i loan dong mau ngay tu khi nhap vidn ndn khong thd sinh thidt gan chin doan. Vide thu thap man mo gan tu cac tre sa sinh tu vong vi suy gan khong ro nguyen nhan, dac biet trong truang hgp gia dinh da co cac tre tu vong vi suy gan rat can thidt, kdt qua giai phau bdnh khong chi lam sang to nguyen nhan tir vong, ma con giiip lap kd hoach chuin bi didu tri du phong cho lan sinh sau [7],
Ba ca bdnh NH duoc bao cao trong nghien ciiu nay la con ciia mot gia dinh, kdt qua mo benh hpc kdt hpp vai bdnh canh lam sang ciia bdnh nhan thii nhat la nhung ca sa khoa hpc qui gid dd chan doan va ciiu song hai nguoi con sau.
B?nh nhan thii 2 dugc didu tri theo phac d6 NH
bang IVIG kdt hop vai thuoc chong oxy hoa, thai sat.. .tu ngay thii 11 sau sinh, tuy dugc ciiu song song thai gian dieu tri tai bdnh vidn kha dai (27 ngay), chi phi didu tri ton kem va thai gian on dinh chiic nang gan can tai 12 thang. Do dupc xac dinh ve nguy co mic NH tu trudc, bdnh nhan thii 3 dugc nhap vidn va didu trj thanh cong theo phac d6 ttr ngay thii 2 sau sinh chi voi 1 lidu IVIG va cac thufic didu tri h6 trp trong 2 thang. Trong dieu kidn nuac ta, vide dieu tri IVIG cho cac ba m? c6 nguy co sinh con NH tu trong thai ky nhu cac tac gia Whingtinton PF va Loprio E [5,10] rit kho khan do chi phi didu tri qua lan ndn didu tri NH chu ydu la didu trj sau sinh. Hai trong ba benh nhan trong nghidn ciiu cua chiing toi dugc ciiu s6ng nha su dyng cac thudc chdng oxy hoa, IVIG, thai sit va cac dieu tri tridu chiing nhu ursodeoxycholic acid, vitamin K, plasma tuai...khong co bdnh nhan nao phai didu fri bing phuang phap thay man va ghep gan nhu nhom bdnh nhan cua Whingtinton PF va F.Rodrigues [2,8,10].
Tap chi GAN MAT VEET NAM so 29-2014 37 Tic gia Eva Maria Christina trong nghien
ciiu trdn tap chi Molecular Cytogenetic thang I nam 2014 bao cao vd ca bdnh NH co mang dot bien thdm doan a canh ngan nhidm sac the so 16, nghien cuu nay ciia chung toi cung buac dSu ghi nhSn mot bdnh nhan mang dot bidn mit doan a nhilm sic thd s6 16 (46XXdeI 16 (q23)/46XX). Day mcri chi la cac nhan xet ghi nhan buac dau ve cac dot bidn nay a cac benh nhkn NH, cixng co the day !a cac dot bidn xuit hidn trdn cac benh nhan NH m6t each trung hgp va khong lidn quan t6i nguydn nhan gay bdnh.
Ket luan va kien nghi
Bdnh ly NH la mpt trong nhimg nguyen nhan gay suy gan sam a tre so sinh. Cac tre mac NH CO thd dugc cuu song ndu dugc chan doan va didu tri som
Can sinh thiet gan, hoac thu thap cac mau b?nh pham sau khi tu vong cac bdnh nhan so sinh suy gan khong ro nguydn nhan de chan doan.
Cac ba me co con da hi tu vong do NH can dupc tu vin va didu trj o Ian co thai sau nham han che anh hucmg ciia NH tai thai nhi.
Ngay sau sinh, cac tre co nguy co bi NH can dugc kham, tu vin va theo doi bdi cac bac sy so sinh va gan mat
Tki li^u tham khao
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Joumal of Pediatric
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4. Giuseppina T, Francesca F., Antonini N et al (2007). Is exchange transfusion a possible treatment for neonatal hemochromatosis. Jour- nal of Hepatology (47), p732-735.
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7. S, Collardeau- Frachon, S Heissat, R.
Bouvier et al (2012). French retrospective mul- ticentric study of neonatal hemochromatosis:
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Pedianics 116 (6), p880-884.
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