Tap chi GAN MAT VIET NAM so 31-2015 49
Hoi chmig than hir & benh nhan Wilson: Nhan ba tru-ong hop durac phat hien tai benh vif n Nhi trung yong
Nguyin Phgm Anh Hoa. Trinh Thi Thuy, Bd Vdn Bo, Bui Thi Kim Oanh, Bgeh Ly Na, Hodng Thi Xuyin, Hodng Vdn Anh, Bui Thi Huang Thiiy, Nguyen Thi Mai Thdo, VU Thi Hd*
Tom dt:
Benh Wilson la benh rdi loan chuydn hoa dong, di tmyen lan fren NST thuong, gay li dong dong qua miic 6 gan, nao, than, giac mac .... Cac b?nh nhan Wilson dugc dieu tri theo nguyen t^c:
Dimg thudc thuc day qua trinh bai tilt ddng qua nudc tieu (D-Penicillamine hoac Trientin), thudc giam hap thu ddng Zinc va kit hgp vdi chi dp an giam dong. Mot sd benh nhan Wilson xuat hien hoi chung than hu sau mot thdri gian dung thudc D-Penicillamine, nguyen nhan co th§ do
Abstract
Wilson disease is a copper metabolism disor- der, inherited in an autosomal recessive, causes excessive copper accumulation in the liver , brain , kidney , cornea .... Therapy for Wilson disease freatment: copper-chelating agents (D- penicillamine or Trientin), Zinc combined low copper diet. Some Wilson patients developed nephrotic syndrome after a period of freatment with D-Penicillamine, the cause of nephrotic syndrome can be caused by side effects of the
l.f>atv4nd^
Benh Wilson dugc Kiner Wilson mo ta lan dau tien nam 1912- Qky la benh di tmyen nam fren NST 13ql4, gay u dgng dong a cac co quan nhu:
Gan, nao, than, giac mac... Cac benh nhan Wilson dugc dieu tri theo nguyen tic: Diing thuoc thuc day qua trinh bai tiet dong qua nudc tieu (D-Peni- cillamine ho^c Trientm), thudc giam hap thu dong Zinc va ket hgp vdi che do an giam ddng.
D-Penicilamine dugc sir dung dieu tri benh Wilson lan dau tien nam 1956. Thudc c6 vai fro
tac dung phu cua thudc D-Penicillamine fren than hoac do u dgng dong gay ton thuong than ciia benh Wilson. Mgt sd bao cao vd cac ca benh Wilson xuat hien hoi chung than hu sau mdt thai gian dieu tri bang D-Penicillamine da dugc xu tri bang each dimg thuoc D-Penicillamine chuyen sang dimg Trientin hoac dung D-Penicil- lamine ket hgp voi cortieoid, Chung toi bao cao ba benh nhan Wilson xu4t hien hpi chung than hu sau mgt thai gian dieu fri bang D-Penicil- lamine.
drug D- Penicillamine on the kidneys or by the accumulation of copper which injury kidney of Wilson's disease. A number of reports about the Wilson patients who developed nephrotic syn- drome after a period of freatment with D-Peni- cillamine were freated by stopping D- penicillamine and switched to Trientin or steroids . We report three patients with Wilson's disease who developed nephrotic syndrome after a period of treatment with D-Penicillamine freatment.
thiic day bai tiet ddng qua nudc tieu, song cung cd cac tac dung phu nhu: Sot, phat ban, protein nieu, thieu mau, giam tieu cau, giam bach cau hat, hgi chimg than hu, ton thuang giac mac, phan ling gidng Lupus...
Hgi chung than hu (HCTH) xuat hien d benh nhan Wilson sau mgt thdi gian dieu tri bang D- Penicillamine da dugc Feller va Shahidi md ta lan dau tien nam 1959 [4]. Nhiing nam tiep theo mgt sd tac gia cimg mo ta mgt sd ca benh tuong tu nhu: Tac gia Adam, Goldman, Maxwell va
* Khoa Gan mgt - Benh vien Nhi Trung uang
50 Tap chi GAN MAT VIET NAM so 31-2015 Latta (1964) [1], Steralied va Scheinberg (1964) [7], Constantmos va cgng su nam 1988 [3], Dr.
anil Kumar va cgng su nam 2013 [2]. Nam 1966 M.Karp, M.Lurie va Z.Yonis [5] md ta benh nhan Wilson xuk hien HCTH sau mgt thdi gian didu tri bing D-Penicillamine va benh nay tii vong vi suy than, hmh anh giai phau benh cua than ciing da dugc md ta vdi tdn thuang chu yeu d te bao bieu mo ong than.
HCTH xuat hien a benh nhan Wilson ngay tai thdi diem chan doan benh ciing da dugc Xiao- Hui Zahuang va cgng su mo ta nam 2008 [8].
Trong cac bao cao nay deu md ta ve cac ca benh Wilson c6 HCTH xuat hien tan mat vdi so lugng b?nh nhan rat it (mdi bao cao chi co tir I den 3 b$nh nhan)
Trong bao cao nay chiing tdi md ta ba benh nhan Wilson xuat hien hgi chung than hu sau mgt thoi gian dieu tri bang D-Penicillamine
2. Bdo cai ca b^nh l.Cabenhl
Benh nhan; Nguyen thi L A , nil 9 mdi, vao vien vi met mdi. Kham: tinh tao, tinh than va van dpng binh thudrng, vang da nhe, khong phii, gan va lach to, tim va phoi binh thudng. Xet nghiem: Bilimbil TP 32.5 mmol/l (Bilimbil TT 15 mmol/l, Bilirmbil GT 17.5 mmol/l), GOT 253 Ul, GPT 290 UI, albumin 26 g/l, protein 59 g/l, ure 3.5 mmol/l, creatinin 36.3 pmol/1, ty le Prothrombin 50%, ceruloplasmin 0.043 g/I, ddng mau 7.8 pmol/1, dong nieu 821 |4,g/24h, cac marker viem gan nhu HbsAg, HCV, HAV, PCR(CMV), PCR(EBV) diu am tinh, protein nieu am tinh. Benh nhan dugc chSn doan xac dinh la benh Wilson ( Theo thang dilm ciia Leipzig 2001) [6]. Tre dugc dilu tri b5ng cac thudc D-Penicillamine (Trolovol) lilu 20mg/kg/ngay, Zinc, Vitamin B6 va chi do an giam dong. Diln biln frong qua trinh dilu tri fre het met mdi, het vang da. Sau 6 thang dilu fri fre xuat hien cac cac dau hieu nhu met mdi, phii, cd chudng, freu it; Xet nghiem: ure 5.3 mmol/l.
creatimn 35.8pmol/l, albumin 19 g/l, protem 50 g/l, cholesterol 10 g/l, protein nieu 281mg/kg/24h, chirc nang gan frong gidi han binh thuQfng, sinh thiet than cd hinh anh lang dgng Hyalin df hka het cac te bao bieu mo dng than, chii yiu d ong lugn gan, mpt so ong than sung phdng biiu md mat diem ban chai. B?nh nhan dugc chdn doan xac dinh la HCTH/ Wil- son. Phuong phap dieu tri: Tiip fric dieu fri D- Penicillamine lilu 20mg/kg/ngay, Zuic, vitamm B6, chi dg an giam ddng ket hgp vdi Pred- nisolon lilu 2mg/kg/ngdy, thudc lgi tieu. Kit qua dieu fri fre het met moi, phu giam dan, tieu tien tot hon, sau 15 ngay dieu tri fre tieu binh thucmg va het phu; cac xet nghidm: ure 3 mmol/l, creatinin 32 mmol/l, albumin mau 30.6g/l, protein mau 60.8 g/l, protein niSu am tinh, chuc nang gan frong gidi han binh thucmg.
Mo benh hpc: lang dpng hyaline d ong than 2. Ca benh 2
Benh nhan: Duong Manh D, nam 16 tudi, benh khdi phat khi fre 12 tudi. Ly do vao vien vi phii, CO chudrng; Tre vao vien frong tinh frang:
Tinh tao, tinh than va van dpng binh thucmg, khong vang da, tim va phdi buih thuang, bung CO chudtig, gan va lach to. Xet nghiem Biluubil TP 15.9 mmol/l (Bihubil TT 11.3 mmol/l. BiUr- mbil GT 4.6 mmol/l), GOT 12 Ul, GPT 76 UI, Ure 3.5 mmol/l, creatinin 50.9 pmol/l, ty le Pro- thrombin 50%, albumin mau 14 g/l, protem mau 39g/l, cemloplasmin 0.05 g/l, ddng mdu 4.2
Tap cM GAN MAT VIET NAM so 31-2015 51 pmol/1, dong nieu 122 pg/24h, protein nieu am
tinh, cac marker viem gan nhu HBsAg, HAV, HCV, PCR(CMV), PCR(EBV) diu am tinh. Tre dugc chan doan xac dinh benh Wilson (theo thang diem Leipzig 2001)[6]. Tre dugc dieu tri bang cac thudc D-Penicillamine (Trolovol) lieu 20mg/kg/ngay, Zinc, Vitamin B6 va chi dp an giam dong. Sau dieu tri fre hit phu, hit c6 chudng va diln bien benh on dinh frong 4 nam.
Sau 4 nam fre xuat hien met moi, tieu it, phu, co chudfng. Cac xet nghiem: Ure 23mmol/l, crea- tinin 148 pmol/1, albumin mau 23 g/l, protein mau 43 g/l, cholesterol 6.1 g/l, protem nieu 231.8 mg/kg/24h, BUN/CREATININ 46, GOT 27 UI, GPT 36 UI, ty le prothrombin 46 %. Chk doan suy than truac than/ HCTH/Wilson. Phuong phap dieu tn: Tiep tuc dilu tri D-Penicillamine lieu 20mg/kg/ngay, Zinc, vitamin B6, che do an giam dong, lgi tieu, bii albumin, can bang nudc dien giai, beiih nhan khong dieu tri dugc Pred- nisolon vi trong qua trinh dieu fri tre co xuat huyet tieu hoa do tang ap luc tTnh mach cira. Ket qua dieu tri fre tieu tot hon, phii va co chudng giam dan va sau 28 ngay tre tieu binh thucmg, hit phil, het co chuong, cac xet nghiem: ure 4 mmol/l, creatinin 83 pmol/l, albumin mau 29 g/l, protein mau 51 g/l, protein ni?u am tinh
Cab?nh3
Benh nhan: Chu The A, nam 9 mdi vao vien vi phu, vang da nhe, vao vien frong tinh frang;
Tinh tao, tinh than va van dpng binh thudng, vang da nhe, phii, co chudng, gan va lach to. Xet nghi?m: Bilimbil TP 25.3 mmol/l (Bilmbil TT 6.7 mmol/l, Biluubil GT 18.6 mmol/l) GOT 136 UI, GPT 71 UI, ure 3.5 mmol/l, creatinin 43.4 pmol/i, ty le prothrombin 39%, albumin mau 23 g/I, protein mau 62 g/l, protein nieu am tinh, cemloplasmin 0.05 g/l, ddng mau 6.4 pmol/1, ddng nieu 84pg/24h, ddng nieu/24h (sau test d- peniciilamine) 1945 pg. Chan doan xac dinh benh Wilson (theo thang diem Leipzig 2001) [6]. Tre dugc dilu fri b4ng cac thuoc D-Penicil- amine (Trolovol) lieu 20mg/kg/ngay, Zinc, vita-
min B6 va che dp an giam dong. Sau dieu fri fre het vang da, het phu, het cd chudrng, theo doi on dinh frong 5 thang. Sau 5 thang dieu tri fre xuat hien cac triSu chung tieu it, phif, co chudmg; Xet nghiem: Ure 23 mmol/l, creatinin 121 pmol/1, al- bumin mau 22.3 g/l, protein mau 50g/l, protein niSu 106mg/kg/24h, BUN/CREATININ 43, GOT 52.8 UI, GPT 22.3 UI, ty le prothrombin 34.9 %. Tre dugc chan doan: Suy than tmdc than/HCTH/ Wilson. Phuang phap dieu tri: Tiep tuc dieu tri D-Penicillamine lieu 20mg/kg/ngay, Zinc, vitamin B6, che do an giam dong ket hgp vdi Prednisolon lieu 2mg/kg/ngay, can bang nudc dien giai, tmyen albumin, thuoc lgi tieu.
Ket qua dieu tri: Tre tieu tien tdt hon, phu va co chudng giam dan. Sau 7 ngay dieu tri fre het phii, het cd chuong, cac xet nghiem: ure 4.6 mmol/l, creatinin 85 pmol/1, albumin mau 43 g/l, protein mau 65g/l, protein nieu am tinh sau 4 thang.
3. Ban luan
Trong y van da co mpt so tac gia mo ta ve HCTH a benh nhan Wilson, moi bao cao ca benh chi md ta tii 1 den 3 benh nhan [1,2,3,4,5,7,8].
HCTH CO the xuat hien nhu mpt frong nhung trieu chung dau tien cua benh Wilson [8] va day co the la hau qua ciia tinh frang u dgng ddng qua miic tai th$n gay ton thucmg than ciia benh Wilson. Mgt so tac gia khac lai nhan thay HCTH xuat hien d benh nhan Wilson sau mpt thai gian dieu tri bang D-penicillamine [1,2,3,4,5] vachiic nang than cai thien khi dimg thuoc D-Penicillamine va thay the bang Trientin [3,5] hoac dimg D-Penicillamine va dieu tri bang cortieoid [2], HCTH xuat hien d nhirng benh nhan nay co the do tac dung phu cua thudc D-penicillamine len than.
Trong 60 benh nhan Wilson theo doi va dieu tri tai Benh vien Nhi Trung Uang tir thang 01 nam 2007 den het thang 12 nam 2013 chi cd 3 benh nhan xuat hien HCTH sau mgt thai gian dieu tri bang D-Penicillamine, ca ba benh nhan deu xuat hien tdn thuang than d cac mire do khac nhau tai cac thdi diem khac nhau. Ca 3 benh
52 Tap chi GAN MAT VIET NAM sd 31-2015 nhan deu du tieu chuan chan doan HCTH, frong do CO 2 benh nhan suy than frirdc than ( benh nhan 2 va benh nhan 3). Do khdng co Trientin thay the nen ca ba ca benh da giir nguyen Ueu D- Peniciliamine song ket hgp vdi dieu tri Pred- nisolon (benh nhan 1 va benh nhan 3), dieu tri trieu chiing. Ca 3 benh nhan deu dn dinh sau dieu tri, tuy nhien tmdng hgp khong dimg dugc pred- nisolon cac tdn thucmg than lau phuc hoi hem.
Trong 3 b?nh nhan ciia chung tdi cd 2 benh nhan suy than trudc than. Tinh frang suy than frudc than la do giam albumin frong benh Wilson vk trong HCTH. Suy than co the lam cho tinh fr^ng HCTH nang ne va khd dieu chinh han, neu khong dieu tri kip thai se tao thanh vong xoan b^nh ly lam tinh frang benh ngay cang nang ne va phiic t^p, cd the din den tu vong [5]. Vi vay van de giam sat chat che chiic nang gan, than va dieu chinh kip thdi nham ban che tdi thieu cac tdn thucmg tdi than
Tir khi mo ta HCTH d benh nhan Wilson sau mgt thdi gian dieu tri bang D-Penicillmine tit nam 1959 [3] den nay chi co mgt sd cac ca benh dugc mo ta va dieu tri. Phucmg phap dieu tri da dugc cac tac gia fren the gidi ap dung cho benh nhan Wilson xuat hien HCTH sau mgt thoi gian dieu tri bang D-Penicillamine c6 hieu qua do la dimg thuoc D-Penicillamine thay the bang Tri- entin [3,5]. Tuy nhien nam 2013 Dr. anil Kumar va cgng su [2] da dieu tri benh nhan Wilson xudt hien HCTH sau mpt thdi gian dung D-Penicil- lamine bang each dung D-Penicillamine chi duy tri Zinc, ket hgp vdi cortieoid va chiic nang than da cai thien. Trong ba benh nhan cua chiing tdi do khong co Trientin thay the chiing toi da giii nguyen lieu D-Penicillamine kit hgp vdi corti- eoid va chiic nang than ciing da cai thien sau dieu tri.
Trong 3 benh nhan ciia chiing toi chi c6 benh nhan thu nhat dugc sinh thiit than (hai benh nhan con lai khong sinh thiit than dugc do yiu td II ciia 2 benh nhan nay luon frong tinh frang thip), va hinh anh giai phau benh chu yiu ton thuong
d tl bao biiu mo dng than. Tdn thuang nay phu hgp vdi hinh anh giai phau benh than da dugc M.Karp, M.liuie and Z.Yonis [5] md ta.
Kien nghi:
Hgi chiing than hu d benh nhan Wilson co thi xay ra do dien bien cua benh ciing co the do tac dung phu cua thuoc D-Penicillamine. Vi vay frong qua trinh chan doan va dieu fri benh Wilson bing D-Penicilamine can kiem fra chiic nang than dinh ky de phat hien va dieu tri kip thai cac tdn thuang than.
Tai lieu tham khao
1. Adams, D.A, Goldman,R,Maxwell,MH, and Latta.H (1964). Nephrotic syndrom asociated with penicilamine therapy of wilson disease.
Amer.J.Med,36, 330.
2. Dr. Anil Kumar Et Al (2013) D-Penicilhnine induced nephrotic syndrome in 11 - year old girl with Wilson disease. Indan J.Pharm. Biol.
Res. 1(4)113-115
3. Constantinos G Et Al (1998). Early onset of Nephrotic syndrome after freatment with D- Penicillamine in a patient with wilson disease.
Vol. 93, No. 12.
4. Feller and Shahidi (1959). The nephrotic syn- ch-ome induced by penicillamine therapy.
Amer. J. Dis. Child, 98,669.
5. M.Karp, M.lurie and Z.Yonis (1966).
Nephrotic syndrome in the course of treatment of Wilson's disease with DL- Penicillamine.
Arch.Dis.Childh,41,684.
6. RFerenci Et Al (2003) Diagnosis and pheno- typpic classification of Wilson disease. Liver.
Int. 139,42.
7. Stemlied va Scheinberg, I. H (1964). Penicil- lamine therapy for hepatolenticular degenera- tion. Amer. J. Path. 36, 699.
8. Xiao-Hui Zahuang Et Al (2008) Analysis of renal rnipaument in children with Wilson's disease. Worid. J. Pediafr, Vol 4 No2.
