Tyrosinemia type 1 in a child, experience of a hematologist. Clinical case
DOI:
https://doi.org/10.15574/SP.2022.123.85Keywords:
hepatosplenomegaly, nephromegaly, tyrosinemia type 1, childrenAbstract
Tyrosinemia is a rare metabolic disease resulting from a metabolic disorder of amino acids, which can occur under the «masks» of various diseases, debut as a hemorrhagic syndrome in children of all age groups, hepatolienal syndrome, hypoglycemia, rickets-like disease, peripheral neuropathy.
Clinical case. In our publication, we report on a girl at the age of 1 year 7 months who had recurrent nosebleeds, which led to a referral to a hematologist. Examination revealed hepatomegaly with impaired liver function (hypoproteinemia, long-term resistant hypoglycemia, coagulopathy) with the development of chronic liver failure, ascites and splenomegaly with signs of hypersplenism, ascites, and nephromegaly. Differential diagnostics was carried out between oncohematological process, myelodysplastic syndrome (MDS) and metabolic disease. Type 1 tyrosinemia (hereditary infantile tyrosinemia (HT-1)) was verified by a combination of clinical and biochemical, molecular genetic studies. Verification of the disease came from the spectrometry of amino acids, acylcarnitines, succinal acetates and molecular genetic studies. Molecular genetic studies in the INVITAE laboratory, USA revealed two pathogenic variants identified in the FAH gene c.1069G>T (p.Glu357*) and c.554-1G>T, which are associated with autosomal recessive tyrosinemia. The emphasis in the publication is on the differential diagnosis, the effectiveness of the treatment of this orphan disease. The method of pathogenetic therapy of HT-1 is described in detail, both with the use of the drug nitisinone (orphadin) registered in Ukraine, a special diet with a low content of phenylalanine / tyrosine, which have a pronounced positive clinical effect and prevent the formation of irreversible disabling disorders. We emphasize the need for early diagnosis of HT-1 and support the Ministry of Health of Ukraine in the initiative of routine neonatal screening for orphan diseases, which include HT-1, since timely treatment improves the quality of life in these patients.
The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Äärelä L, Hiltunen P, Soini T, Vuorela N, Huhtala H, Nevalainen PI, Heikinheimo M, Kivelä L, Kurppa K. (2020). Type 1 tyrosinemia in Finland: a nationwide study. Orphanet J Rare Dis. 15 (1): 281. https://doi.org/10.1186/s13023-020-01547-w; PMid:33046095 PMCid:PMC7549233
Aktuglu Zeybek AC, Kiykim E, Soyucen E. (2015). Hereditary tyrosinemia type 1 in Turkey: twenty year single-center experience. Pediatr Int. 57: 281-289. https://doi.org/10.1111/ped.12503; PMid:25223216
Andre N, Roquelaure B, Jubin V, Ovaert C. (2005). Successful treatment of severe cardiomyopathy with NTBC in a child with tyrosinaemia type I. J Inherit Metab Dis. 28: 103-106. https://doi.org/10.1007/s10545-005-5085-4; PMid:15702412
Bay A, Karaoglu O, Sivasli E, Leblebisatan G, Keskin M. (2012). An infant with prolonged circumcision bleeding and unexplained coagulopathy. Indian J Hematol Blood Transfus. 28: 181-183. https://doi.org/10.1007/s12288-011-0115-x; PMid:23997457 PMCid:PMC3422388
Baydakova GV, Ivanova TA, Mikhaylova SV, Saydaeva DK, Dzhudinova LL, Akhlakova AI, Gamzatova AI, Bychkov IO, Zakharova EY. (2019). The Unique Spectrum of Mutations in Patients with Hereditary Tyrosinemia Type 1 in Different Regions of the Russian Federation. JIMD Rep. 45: 89-93. https://doi.org/10.1007/8904_2018_144; PMid:30414057 PMCid:PMC6336551
Blohm ME, Vesterling-Horner D, Calaminus G, Gobel U. (1998). Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatr Hematol Oncol. 15: 135-142. https://doi.org/10.3109/08880019809167228; PMid:9592840
Castilloux J, Laberge AM, Martin SR, Lallier M, Marchand V. (2007). «Silent» tyrosinemia presenting as hepatocellular carcinoma in a 10-year-old girl. J Pediatr Gastroenterol Nutr. 44: 375-377. https://doi.org/10.1097/MPG.0b013e31802f640c; PMid:17325560
Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CDM, Grompe M, Mitchell G, Waisbren SE, Gucsavas-Calikoglu M, Wasserstein MP, Coakley K, Scott CR. (2017). Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 19: 12. https://doi.org/10.1038/gim.2017.101; PMid:28771246 PMCid:PMC5729346
Couce ML, Dalmau J, del Toro M. (2011). Tyrosinemia type 1 in Spain: mutational analysis, treatment and long-term outcome. Pediatr Int. 53: 985-989. https://doi.org/10.1111/j.1442-200X.2011.03427.x; PMid:21752152
Couce ML, Sánchez-Pintos P, Aldámiz-Echevarría L, Vitoria I, Navas V, Martín-Hernández E, García-Volpe C, Pintos G, Peña-Quintana L, Hernández T, Gil D, Sánchez-Valverde F, Bueno M, Roca I, López-Ruzafa E, Díaz-Fernández C. (2019). Evolution of tyrosinemia type 1 disease in patients treated with nitisinone in Spain. Medicine (Baltimore). 98 (39): e17303. https://doi.org/10.1097/MD.0000000000017303; PMid:31574857 PMCid:PMC6775438
Dou LM, Fang LJ, Wang XH, Lu W, Chen R, Li LT, Zhao J, Wang JS. (2013). Mutation analysis of FAH gene in patients with tyrosinemia type 1. Zhonghua Er Ke Za Zhi. 51 (4): 302-307.
El-Karaksy H, Fahmy M, El-Raziky M. (2011). Hereditary tyrosinemia type 1 from a single center in Egypt: clinical study of 22 cases. World J Pediatr. 7: 224-231. https://doi.org/10.1007/s12519-011-0287-3; PMid:21633861
Gale GB, O'Connor DM, Chu JY. (1988). Normal values of alpha-fetoprotein in neonates and infants. Pediatrics. 82: 138.
González-Lamuño D, Sánchez-Pintos P, Andrade F, Couce ML, Aldámiz-Echevarría L. (2021). Treatment adherence in tyrosinemia type 1 patients. Orphanet J Rare Dis. 16 (1): 256. https://doi.org/10.1186/s13023-021-01879-1; PMid:34082789 PMCid:PMC8173906
Kulikova KS, Kalinchenko NYu, Sibileva EN, Vasil'eva EV, Petrov VM, Tul'pakov AN. (2015). Hypophosphatasia: the clinical description of 3 cases of the disease with the molecular-genetic verification of the diagnosis. Problems of Endocrinology. 61 (3): 37-42. https://doi.org/10.14341/probl201561337-42
Larochelle J, Alvarez F, Bussières JF et al. (2012). Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec. Mol Genet Metab. 107: 49-54. https://doi.org/10.1016/j.ymgme.2012.05.022; PMid:22885033
Megdadi NA, Almigdad AK, Alakil MO, Alqiam SM, Rababah SG, Dwiari MA. (2021). Hereditary Tyrosinemia Type 1 in Jordan: A Retrospective Study.Int J Pediatr. 2021: 3327277. https://doi.org/10.1155/2021/3327277; PMid:34899923 PMCid:PMC8660245
Meissner T, Betz RC, Pasternack SM, Eigelshoven S, Ruzicka T, Kruse R et al. (2008). Richner-Hanhart syndrome detected by expanded newborn screening. Pediatr Dermatol. 25: 378-380. https://doi.org/10.1111/j.1525-1470.2008.00687.x; PMid:18577048
Michalski A, Leonard JV, Taylor DS. (1988). The eye and inherited metabolic disease: a review. J R Soc Med. 81: 286-290. https://doi.org/10.1177/014107688808100517; PMid:3290483 PMCid:PMC1291590
Mirani S, Poojari V, Shetty NS, Shah I. (2021). Outcome of Tyrosinemia Type 1 in Indian Children. J Clin Exp Hepatol. 11 (1): 9-13. https://doi.org/10.1016/j.jceh.2020.07.002; PMid:33679043 PMCid:PMC7897851
Mitchell GA, Grompe M, Lambert M, Tanguay RM. (2014). Hypertyrosinemia. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill. URL: http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62673883.
Mohamed S, Kambal MA, Al Jurayyan NA et al. (2013). Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy. BMC Res Notes. 6: 362. https://doi.org/10.1186/1756-0500-6-362; PMid:24016420 PMCid:PMC3846631
MOZ Ukrainy. (2021). Pro zabezpechennia rozshyrennia neonatalnykh skryninhovykh prohram dlia novonarodzhenykh dlia stvorennia novoi systemy neonatalnoho masovoho skryninhu v Ukraini. Nakaz Ministerstva okhorony zdorov'ia Ukrainy vid 01.10.2021 No. 2142. URL: https://zakon.rada.gov.ua/laws/show/z1403-21#Text.
Nakamura K, Matsumoto S, Mitsubuchi H, Endo F. (2015). Diagnosis and treatment of hereditary tyrosinemia in Japan. Pediatr Int. 57: 37-40. https://doi.org/10.1111/ped.12550; PMid:25443793
Neto JS, Leite KMR, Porta A et al. (2014). HCC prevalence and histopathological findings in liver explants of patients with hereditary tyrosinemia type 1. Pediatr Blood Cancer. 61: 1584-1589. https://doi.org/10.1002/pbc.25094; PMid:24852359
Ozcan HN, Karcaaltincaba M, Pektas E, Sivri HS, Oguz B, Dursun A, Tokatli A, Coskun T, Haliloglu M. (2019). Imaging liver nodules in tyrosinemia type-1: A retrospective review of 16 cases in a tertiary pediatric hospital. Eur J Radiol. 116: 41-46. https://doi.org/10.1016/j.ejrad.2019.04.016; PMid:31153572
Rafati M, Mohamadhashem F, Hoseini A, Ramandi SD, Ghaffari SR. (2016). Prenatal Diagnosis of Tyrosinemia Type 1 Using Next Generation Sequencing. Fetal Pediatr Pathol. 35 (4): 282-285. https://doi.org/10.3109/15513815.2016.1167149; PMid:27093575
Raimann E, Cornejo V, Arias C, Cabello JF, Castro G, Fernández E, de la Parra A. (2012). Clinical follow up of Chilean patients with tyrosinemia type 1 treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-ciclohexanedione (NTBC). Rev Med Chil. 140 (2): 169-175. https://doi.org/10.4067/S0034-98872012000200004; PMid:22739945
Schady DA, Roy A, Finegold MJ. (2015). Liver tumors in children with metabolic disorders. Transl Pediatr. 4: 290-303.
Schlune A, Thimm E, Herebian D, Spiekerkoetter U. (2012). Single dose NTBC-treatment of hereditary tyrosinemia type I. J Inherit Metab Dis. 35: 831-836. https://doi.org/10.1007/s10545-012-9450-9; PMid:22307209
Tang Y, Kong Y. (2021). Hereditary tyrosinemia type: newborn screening, diagnosis and treatment. Zhejiang Da Xue Xue Bao Yi Xue Ban. 50 (4): 514-523. https://doi.org/10.3724/zdxbyxb-2021-0255; PMid:34704422 PMCid:PMC8777462
Van Ginkel WG, Pennings JP, van Spronsen FJ. (2017). Liver Cancer in Tyrosinemia Type 1. Adv Exp Med Biol. 959: 101-109. https://doi.org/10.1007/978-3-319-55780-9_9; PMid:28755188
Van Spronsen FJ, Bijleveld CM, van Maldegem BT, Wijburg FA. (2005). Hepatocellular carcinoma in hereditary tyrosinemia type I despite 2-(2 nitro-4-3 trifluoro- methylbenzoyl)-1, 3-cyclohexanedione treatment. J Pediatr Gastroenterol Nutr. 40: 90-93. https://doi.org/10.1097/00005176-200501000-00017; PMid:15625434
Van Spronsen FJ, van Rijn M, Meyer U, Das AM. (2017). Dietary Considerations in Tyrosinemia Type I. Adv Exp Med Biol. 959: 197-204. https://doi.org/10.1007/978-3-319-55780-9_18; PMid:28755197
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Modern pediatrics. Ukraine
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “MODERN PEDIATRICS. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal “MODERN PEDIATRICS. UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
