|
|
|
| Hereditary tyrosinemia type Ⅰ: newborn screening, diagnosis and treatment |
TANG Yue( ),KONG Yuanyuan() |
| Department of Newborn Screening, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100020, China |
|
|
|
Abstract Hereditary tyrosinemia type Ⅰ (HT-1) is a severe autosomal recessive inherited metabolic disease. Due to the deficiency of fumarylacetoacetase hydrolase (FAH), the toxic metabolites are accumulated in the body, resulting in severe liver dysfunction, renal tubular dysfunctions, neurological crises, and the increased risk of hepatocellular carcinoma. Clinical symptoms typically begin at 1?year after the birth; the prognosis of patients is poor if they are not treated timely. Succinylacetone is a specific and sensitive marker for HT-1, and the screening in newborns can make early diagnosis of HT-1 at the asymptomatic stage. The diagnosis of HT-1 can be confirmed based on the characteristic biochemical findings and molecular testing of mutations in both alleles of FAHgene. Combined treatment with nitisinone and a low tyrosine diet may significantly improve outcomes for patients. Liver transplantation is an effective treatment in cases where nitisinone is not available. Some novel HT-1 treatments are in clinical trials, including enzyme replacement therapy, hepatocyte transplantation and gene-targeted therapy.
|
|
Received: 07 May 2021
Published: 01 November 2021
|
|
|
|
Corresponding Authors:
KONG Yuanyuan
E-mail: tangyue@mail.ccmu.edu.cn;kongyuanyuan1971@163.com
|
遗传性酪氨酸血症Ⅰ型及其筛查和诊治进展
遗传性酪氨酸血症Ⅰ型（HT-1）是因延胡索酰乙酰乙酸水解酶缺陷所致的一种常染色体隐性遗传代谢病。患者体内酪氨酸分解代谢受阻，毒性代谢物蓄积，导致严重肝功能损害、肾小管功能障碍及神经危象，患肝细胞癌风险加大。本病多于婴儿期起病，未获得及时诊治者总体预后不佳。新生儿筛查可早期发现无症状患儿，以琥珀酰丙酮作为筛查指标具有较高的特异度及敏感度。依据典型生化指标改变及分子遗传学检测结果可帮助明确诊断。尼替西农联合低酪氨酸饮食治疗可显著改善患者预后，对于没有条件使用尼替西农患者，肝移植是有效的治疗手段。酶替代疗法、肝细胞移植及基因治疗仍处于临床研究阶段，有望日后为患者提供新的治疗方案。
关键词：
新生儿筛查,
遗传性酪氨酸血症Ⅰ型,
琥珀酰丙酮,
尼替西农,
肝移植,
综述
|
|
| [1] |
MITCHELL G A, GROMPE M, LAMBERT M, et al. Hypertyrosinemia[M]//SCRIVER C R, BEAUDET A L, SLY W S, et al. Metabolic & molecular bases of inherited disease. New York: McGraw Hill, 2001: 1777-1806
|
|
|
| [2] |
ANGILERI F, BERGERON A, MORROW G, et al. Geographical and ethnic distribution of mutations of the fumarylacetoacetate hydrolase gene in hereditary tyrosinemia type 1[J]. JIMD Rep, 2015, 19: 43-58
|
|
|
| [3] |
DE BRAEKELEER M, LAROCHELLE J. Genetic epidemiology of hereditary tyrosinemia in Quebec and in Saguenay-Lac-St-Jean[J]. Am J Hum Genet, 1990, 47(2): 302-307
|
|
|
| [4] |
童 凡, 杨茹莱, 刘 畅, 等. 新生儿酪氨酸血症筛查及基因谱分析[J]. 浙江大学学报(医学版), 2019, 48(4): 459-464
TONG Fan, YANG Rulai, LIU Chang, et al. Screening for hereditary tyrosinemia and genotype analysis in newborns[J]. Journal of Zhejiang University (Medical Sciences), 2019, 48(4): 459-464. (in Chinese)
|
|
|
| [5] |
CAO Y Y, ZHANG Y L, DU J, et al. Compound mutations (R237X and L375P) in the fumarylacetoacetate hydrolase gene causing tyrosinemia type Ⅰ in a Chinese patient[J]. Chin Med J, 2012, 125(12): 2132-2136
|
|
|
| [6] |
杨 楠, 韩连书, 叶 军, 等. 三例酪氨酸血症Ⅰ型患者的临床表现及基因突变分析[J]. 中华医学遗传学杂志, 2012, 29(6): 648-652
YANG Nan, HAN Lianshu, YE Jun, et al. Analysis of clinical data and genetic mutations in three Chinese patients with tyrosinemia type Ⅰ[J]. Chinese Journal of Medical Genetics, 2012, 29(6): 648-652. (in Chinese)
|
|
|
| [7] |
窦丽敏, 方玲娟, 王晓红, 等. 酪氨酸血症Ⅰ型的临床及基因突变分析[J]. 中华儿科杂志, 2013, 51(4): 302-307. DOU Limin, FANG Lingjuan, WANG Xiaohong, et al.Mutation analysis of FAH gene in patients with tyrosinemia type Ⅰ[J]. Chinese Journal of Pediatrics, 2013, 51(4): 302-307. (in Chinese)
|
|
|
| [8] |
郭 莉, 焦保权, 刘 芳. 一例不伴琥珀酰丙酮增高的酪氨酸血症Ⅰ型患儿的临床及遗传学分析[J]. 中华医学遗传学杂志, 2019, 36(5): 472-476
GUO Li, JIAO Baoquan, LIU Fang. Clinical and genetic analysis of a patient with tyrosinemia type Ⅰ but without elevated succinylacetone[J]. Chinese Journal of Medical Genetics, 2019, 36(5): 472-476 (in Chinese)
|
|
|
| [9] |
MAKC M, LAMC W, CHIMS, et al.Biochemical and molecular diagnosis of tyrosinemia type Ⅰ with two novel FAH mutations in a Hong Kong Chinese patient: recommendation for expanded newborn screening in Hong Kong[J]Clin Biochem, 2013, 46( 1-2): 155-159.
doi: 10.1016/j.clinbiochem.2012.09.010
|
|
|
| [10] |
JORQUERAR, TANGUAYR M. Fumarylacetoacetate, the metabolite accumulating in hereditary tyrosinemia, activates the ERK pathway and induces mitotic abnormalities and genomic instability[J]Hum Mol Genet, 2001, 10( 17): 1741-1752.
doi: 10.1093/hmg/10.17.1741
|
|
|
| [11] |
BLIKSRUDY T, ELLINGSENA, BJ?R?SM. Fumarylacetoacetate inhibits the initial step of the base excision repair pathway: implication for the pathogenesis of tyrosinemia type Ⅰ[J]J Inherit Metab Dis, 2013, 36( 5): 773-778.
doi: 10.1007/s10545-012-9556-0
|
|
|
| [12] |
YANG F, LI J, DENG H, et al. GSTZ1-1 deficiency activates NRF2/IGF1R axis in HCC via accumulation of oncometabolite succinylacetone[J/OL]. EMBO J, 2019, 38(15): e101964
|
|
|
| [13] |
SASSAS, KAPPASA. Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone[J]J Clin Invest, 1983, 71( 3): 625-634.
doi: 10.1172/JCI110809
|
|
|
| [14] |
BISSELLD M, LAIJ C, MEISTERR K, et al.Role of delta-aminolevulinic acid in the symptoms of acute porphyria[J]Am J Med, 2015, 128( 3): 313-317.
doi: 10.1016/j.amjmed.2014.10.026
|
|
|
| [15] |
ROTHK S, CARTERB E, HIGGINSE S. Succinylacetone effects on renal tubular phosphate metabolism: a model for experimental renal Fanconi syndrome[J]Proc Soc Exp Biol Med, 1991, 196( 4): 428-431.
doi: 10.3181/00379727-196-43211
|
|
|
| [16] |
BERGERR, VAN FAASSENH, SMITHG P A. Biochemical studies on the enzymatic deficiencies in hereditary tyrosinemia[J]Clin Chim Acta, 1983, 134( 1-2): 129-141.
doi: 10.1016/0009-8981(83)90191-2
|
|
|
| [17] |
BAUMANNU, PREECEM A, GREENA, et al.Hyperinsulinism in tyrosinaemia type Ⅰ[J]J Inherit Metab Dis, 2005, 28( 2): 131-135.
doi: 10.1007/s10545-005-5517-1
|
|
|
| [18] |
PRIESTLEYJ R C, ALHARBIH, CALLAHANK P, et al.The importance of succinylacetone: tyrosinemia type Ⅰ presenting with hyperinsulinism and multiorgan failure following normal newborn screening[J]Int J Neonatal Screen, 2020, 6( 2): 39.
doi: 10.3390/ijns6020039
|
|
|
| [19] |
WEINBERGA G, MIZEC E, WORTHENH G. The occurrence of hepatoma in the chronic form of hereditary tyrosinemia[J]J Pediatr, 1976, 88( 3): 434-438.
doi: 10.1016/S0022-3476(76)80259-4
|
|
|
| [20] |
ARORAN, STUMPERO, WRIGHTJ, et al.Cardiomyopathy in tyrosinaemia type Ⅰ is common but usually benign[J]J Inherit Metab Dis, 2006, 29( 1): 54-57.
doi: 10.1007/s10545-006-0203-5
|
|
|
| [21] |
MOHAMEDS, KAMBALM A, AL JURAYYANN A, et al.Tyrosinemia type Ⅰ: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy[J]BMC Res Notes, 2013, 6( 1): 362.
doi: 10.1186/1756-0500-6-362
|
|
|
| [22] |
VAN SPRONSENF J, THOMASSEY, SMITG P A, et al.Hereditary tyrosinemia type Ⅰ: a new clinical classification with difference in prognosis on dietary treatment[J]Hepatology, 1994, 20( 5): 1187-1191.
doi: 10.1002/hep.1840200513
|
|
|
| [23] |
BERRYG T. Galactosemia: when is it a newborn screening emergency?[J]Mol Genet Metab, 2012, 106( 1): 7-11.
doi: 10.1016/j.ymgme.2012.03.007
|
|
|
| [24] |
LAFHALK, SABIRE S, CHEGGOURM, et al.Update of a colorimetric method for quantitative determination of galactose in blood samples: a simple and rapid method for the early detection of inherited metabolic diseases[J]Carbohydr Res, 2020, 108179.
doi: 10.1016/j.carres.2020.108179
|
|
|
| [25] |
张建蕊, 孙丽莹, 朱志军, 等. 酪氨酸血症Ⅰ型行肝移植一例报告[J]. 中华器官移植杂志, 2017, 38(10): 619-621
ZHANG Jianrui, SUN Liying, ZHU Zhijun, et al. A case report of a liver transplantation for hereditary tyrosinemia type Ⅰ[J]. Chinese Journal of Organ Transplantation, 2017, 38(10): 619-621. (in Chinese)
|
|
|
| [26] |
GIGUERE Y, BERTHIER M T. Newborn screening for hereditary tyrosinemia type Ⅰ in Quebec: update[J]. Adv Exp Med Biol, 2017, 959: 139-146
|
|
|
| [27] |
MAGERAM J, GUNAWARDENAN D, HAHNS H, et al.Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type Ⅰ[J]Mol Genet Metab, 2006, 88( 1): 16-21.
doi: 10.1016/j.ymgme.2005.12.005
|
|
|
| [28] |
CHINSKY J M, SINGH R, FICICIOGLU C, et al. Diagnosis and treatment of tyrosinemia type Ⅰ: a US and Canadian consensus group review and recommendations[J]. Genet Med, 2017, 19(12)
|
|
|
| [29] |
STINTONC, GEPPERTJ, FREEMANK, et al.Newborn screening for tyrosinemia type Ⅰ using succinylacetone - a systematic review of test accuracy[J]Orphanet J Rare Dis, 2017, 12( 1): 48.
doi: 10.1186/s13023-017-0599-z
|
|
|
| [30] |
ALLARDP, GRENIERA, KORSONM S, et al.Newborn screening for hepatorenal tyrosinemia by tandem mass spectrometry: analysis of succinylacetone extracted from dried blood spots[J]Clin Biochem, 2004, 37( 11): 1010-1015.
doi: 10.1016/j.clinbiochem.2004.07.006
|
|
|
| [31] |
DE JESúSV R, ADAMB W, MANDELD, et al.Succinylacetone as primary marker to detect tyrosinemia type Ⅰ in newborns and its measurement by newborn screening programs[J]Mol Genet Metab, 2014, 113( 1-2): 67-75.
doi: 10.1016/j.ymgme.2014.07.010
|
|
|
| [32] |
ADAMB W, HALLE M, MEREDITHN K, et al.Performance of succinylacetone assays and their associated proficiency testing outcomes[J]Clin Biochem, 2012, 45( 18): 1658-1663.
doi: 10.1016/j.clinbiochem.2012.08.007
|
|
|
| [33] |
BLACKBURNP R, HICKEYR D, NACER A, et al.Silent tyrosinemia type Ⅰ without elevated tyrosine or succinylacetone associated with liver cirrhosis and hepatocellular carcinoma[J]Hum Mutat, 2016, 37( 10): 1097-1105.
doi: 10.1002/humu.23047
|
|
|
| [34] |
YANGH, AL-HERTANIW, CYRD, et al.Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency[J]J Med Genet, 2017, 54( 4): 241-247.
doi: 10.1136/jmedgenet-2016-104289
|
|
|
| [41] |
VAN SPRONSEN F J, VAN RIJN M, MEYER U, et al. Dietary considerations in tyrosinemia type Ⅰ[J]. Adv Exp Med Biol, 2017, 959: 197-204
|
|
|
| [42] |
YILMAZO, DALYA, PINTOA, et al.Natural protein tolerance and metabolic control in patients with hereditary tyrosinaemia type Ⅰ[J]Nutrients, 2020, 12( 4): 1148.
doi: 10.3390/nu12041148
|
|
|
| [43] |
VAN GINKELW G, VAN REEMSTH E, KIENSTRAN S, et al.The effect of various doses of phenylalanine supplementation on blood phenylalanine and tyrosine concentrations in tyrosinemia type Ⅰ patients[J]Nutrients, 2019, 11( 11): 2816.
doi: 10.3390/nu11112816
|
|
|
| [44] |
B?RHOLDF, MEYERU, NEUGEBAUERA K, et al.Hepatorenal tyrosinaemia: impact of a simplified diet on metabolic control and clinical outcome[J]Nutrients, 2020, 13( 1): 134.
doi: 10.3390/nu13010134
|
|
|
| [35] |
LINDSTEDTS. Treatment of hereditary tyrosinaemia type Ⅰ by inhibition of 4-hydroxyphenylpyruvate dioxygenase[J]Lancet, 1992, 340( 8823): 813-817.
doi: 10.1016/0140-6736(92)92685-9
|
|
|
| [36] |
DE LAETC, DIONISI-VICIC, LEONARDJ V, et al.Recommendations for the management of tyrosinaemia type Ⅰ[J]Orphanet J Rare Dis, 2013, 8( 1): 8.
doi: 10.1186/1750-1172-8-8
|
|
|
| [37] |
VAN GINKELW G, RODENBURGI L, HARDINGC O, et al.Long-term outcomes and practical considerations in the pharmacological management of tyrosinemia type Ⅰ[J]Paediatr Drugs, 2019, 21( 6): 413-426.
doi: 10.1007/s40272-019-00364-4
|
|
|
| [38] |
Quebec NTBC Study Group, ALVAREZ F, ATKINSON S, et al. The Quebec NTBC study[J]. Adv Exp Med Biol, 2017, 959: 187-195
|
|
|
| [39] |
VAN GINKEL W G, PENNINGS J P, VAN SPRONSEN F J. Liver cancer in tyrosinemia type Ⅰ[J]. Adv Exp Med Biol, 2017, 959: 101-109
|
|
|
| [40] |
MAYORANDANS, MEYERU, GOKCAYG, et al.Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice[J]Orphanet J Rare Dis, 2014, 9( 1): 107.
doi: 10.1186/s13023-014-0107-7
|
|
|
| [45] |
SPIEKERKOETTER U, COUCE M L, DAS A M, et al. Long-term safety and outcomes in hereditary tyrosinaemia type Ⅰ with nitisinone treatment: a 15-year non-interventional, multicentre study[J]. Lancet Diabetes Endocrinol, 2021, 9(7): 427-435
|
|
|
| [46] |
VAN GINKELW G, JAHJAR, HUIJBREGTSS C J, et al.Neurocognitive outcome in tyrosinemia type Ⅰ patients compared to healthy controls[J]Orphanet J Rare Dis, 2016, 11( 1): 87.
doi: 10.1186/s13023-016-0472-5
|
|
|
| [47] |
VAN GINKEL W G, JAHJA R, HUIJBREGTS S C J, et al. Neurological and neuropsychological problems in tyrosinemia type Ⅰ patients[J]. Adv Exp Med Biol, 2017, 959: 111-122
|
|
|
| [48] |
VAN VLIETK, VAN GINKELW G, JAHJAR, et al.Emotional and behavioral problems, quality of life and metabolic control in NTBC-treated tyrosinemia type Ⅰpatients[J]Orphanet J Rare Dis, 2019, 14( 1): 285.
doi: 10.1186/s13023-019-1259-2
|
|
|
| [49] |
DASA M. Clinical utility of nitisinone for the treatment of hereditary tyrosinemia type-Ⅰ (HT-1)[J]Appl Clin Genet, 2017, 43-48.
doi: 10.2147/TACG.S113310
|
|
|
| [50] |
WISSE R P, WITTEBOL-POST D, VISSER G, et al. Corneal depositions in tyrosinaemia type Ⅰ during treatment with Nitisinone[J]. BMJ Case Rep, 2012, 2012: bcr 2012006301
|
|
|
| [51] |
DAWSONC, RAMACHANDRANR, SAFDARS, et al.Severe neurological crisis in adult patients with tyrosinemia type Ⅰ[J]Ann Clin Transl Neurol, 2020, 7( 9): 1732-1737.
doi: 10.1002/acn3.51160
|
|
|
| [52] |
UCARH K, TUMGORG, KORD, et al.A case report of a very rare association of tyrosinemia type Ⅰ and pancreatitis mimicking neurologic crisis of tyrosinemia type Ⅰ[J]Balkan Med J, 2016, 33( 3): 370-372.
doi: 10.5152/balkanmedj.2016.141074
|
|
|
| [53] |
MAIORANA A, MALAMISURA M, EMMA F, et al. Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1 [J]. Mol Genet Metab, 2014, 113(3): 188-193
|
|
|
| [54] |
LIUY, LUOY, XIAL, et al.Living‐donor liver transplantation for children with tyrosinemia type Ⅰ[J]J Dig Dis, 2020, 21( 3): 189-194.
doi: 10.1111/1751-2980.12846
|
|
|
| [55] |
KAWATRAA, DHANKHARR, MOHANTYA, et al.Biomedical applications of microbial phenylalanine ammonia lyase: current status and future prospects[J]Biochimie, 2020, 142-152.
doi: 10.1016/j.biochi.2020.08.009
|
|
|
| [56] |
HENDRIKSEN M, HOLMBERG LARSSONA, SVENSSON GELIUSS, et al.Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia[J]Sci Rep, 2020, 10( 1): 1315.
doi: 10.1038/s41598-020-57913-y
|
|
|
| [57] |
NAJIMIM, DEFRESNEF, SOKALE M. Concise review: updated advances and current challenges in cell therapy for inborn liver metabolic defects[J]Stem Cells Transl Med, 2016, 5( 8): 1117-1125.
doi: 10.5966/sctm.2015-0260
|
|
|
| [58] |
RIBES-KONINCKXC, IBARSE P, CALZADO AGRASOTM á, et al.Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases[J]Cell TransPlant, 2012, 21( 10): 2267-2282.
doi: 10.3727/096368912X637505
|
|
|
| [59] |
ANDERSONT N, ZARRINPARA. Hepatocyte transplantation: past efforts, current technology, and future expansion of therapeutic potential[J]J Surg Res, 2018, 48-55.
doi: 10.1016/j.jss.2018.01.031
|
|
|
| [60] |
STéPHENNEX, DEBRAYF G, SMETSF, et al.Hepatocyte transplantation using the domino concept in a child with tetrabiopterin nonresponsive 1phenylketonuria[J]Cell TransPlant, 2012, 21( 12): 2765-2770.
doi: 10.3727/096368912X653255
|
|
|
| [61] |
THOMPSONW S, MONDALG, VANLITHC J, et al.The future of gene-targeted therapy for hereditary tyrosinemia type Ⅰ as a lead indication among the inborn errors of metabolism[J]Expert Opin Orphan Drugs, 2020, 8( 7): 245-256.
doi: 10.1080/21678707.2020.1791082
|
|
|
| [62] |
KAISER R A, MAO S A, GLORIOSO J, et al. Lentiviral vector-mediated gene therapy of hepatocytes ex vivo for autologous transplantation in swine[J]. J Vis Exp,2018, 4(141): 10
|
|
|
| [63] |
HICKEYR D, NICOLASC T, ALLENK, et al.Autologous gene and cell therapy provides safe and long-term curative therapy in a large pig model of hereditary tyrosinemia type Ⅰ[J]Cell TransPlant, 2019, 28( 1): 79-88.
doi: 10.1177/0963689718814188
|
|
|
| [64] |
VANLITHC, GUTHMANR, NICOLASC T, et al.Curative ex vivo hepatocyte-directed gene editing in a mouse model of hereditary tyrosinemia type Ⅰ[J]Hum Gene Ther, 2018, 29( 11): 1315-1326.
doi: 10.1089/hum.2017.252
|
|
|
| [65] |
VANLITHC J, GUTHMANR M, NICOLASC T, et al.Ex vivo hepatocyte reprograming promotes homology-directed DNA repair to correct metabolic disease in mice after transplantation[J]Hepatol Commun, 2019, 3( 4): 558-573.
doi: 10.1002/hep4.1315
|
|
|
| [66] |
KAISERR A, NICOLASC T, ALLENK L, et al.Hepatotoxicity and toxicology of in vivo lentiviral vector administration in healthy and liver-injury mouse models[J]Hum Gene Ther Clin Dev, 2019, 30( 2): 57-66.
doi: 10.1089/humc.2018.249
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
