Türkiye'deki Ulusal Yenidoğan Tarama Programı Tarafından Metabolizma Bölümüne Yönlendirilen Yenidoğanlarin Tanı ve Tedavisi: Beş Yıllık Tek Merkez Deneyimi
Abstract
Amaç: Bu çalışmanın amacı, Türkiye Ulusal Yenidoğan Tarama Programı (UYTP)’de tarama yapılan kalıtsal metabolik hastalık şüphesiyle merkezimize yönlendirilen yenidoğanların biyokimyasal ve genetik testleri ile tedavi planlarını araştırmaktı.
Gereç ve Yöntemler: Ocak 2019 ile Kasım 2023 tarihleri arasında UYTP tarafından yönlendirilen bebeklerin tıbbi kayıtları geriye dönük tarandı. Şüpheli biotinidaz eksikliği (BE) için plazma biyotinidaz aktivitesi ve BTD gen analizsonuçları, fenilketonüri (FKÜ) şüphesi için plazma fenilalanin ve PAH gen analizi ile birlikte tedavi bilgileri araştırıldı.
Bulgular: Yetmiş-sekizi (%54.5) şüpheli BE ve 65’i (%45.5) şüpheli FKÜ olmak üzere toplam 143 bebek dahil edildi. Yüksek plazma fenilalanin seviyelerine sahip olanların 23’üne (%35.4) PAH gen analizi yapılmış, bunların %86.9’unda biallelik variant saptanmıştı. Beş hastada sapropterin-diyet kombinasyon tedavisine, üç hastada diyet tedavisine ve bir hastada sapropterin tedavisine başlanmıştı. Şüpheli BE ile yönlendirilen bebeklerin ilk serum biyotinidaz aktivite ölçümünde, %48.7’sinde heterozigot eksiklik, %39.7’sinde kısmi eksiklik ve %10.3’ünde derin eksiklik saptanmıştı. Şüpheli BE olan bebeklerin %79.5’ine BTD gen analizi yapılmış ve %50 oranında biallelik varyant saptanmıştı. Kırk altı hastaya (%59) biyotin tedavisi başlanmıştı.
Sonuç: Çalışmamızda, beş yıllık süre boyunca UYTP tarafından yönlendirilen bebeklerin yaklaşık üçte birinde ilgili hastalığın biallelik varyantları bulunduğu gösterildi. Araştırmamız, ülkemizde UYTP üzerine yapılan az sayıdaki çalışmalardan biridir ve FKÜ ve BE’nin tanı ve tedavi sürecini sunmaktadır.
References
- Kaplan S, Pinar G, Kaplan B, Aslantekin F, Karabulut E, Ayar B, et al. The Prevalence of Consanguineous Marriages and Affecting Factors in Turkey: A National Survey. J Biosoc Sci 2016;48:616-30.
- https://hsgm.saglik.gov.tr/tr/tarama-programlari/ntp.html. Access Date: January 20, 2024
- Tezel B, Dilli D, Bolat H, Sahman H, Ozbas S, Acican D, et al. The development and organization of newborn screening programs in Turkey. J Clin Lab Anal. 2014;28:63-9.
- Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, et al. The Genetic Landscape and Epidemiology of Phenylketonuria. Am J Hum Genet. 2020;107:234-50.
- Rajabi F, Rohr F, Wessel A, Martell L, Dobrowolski SF, Guldberg P, et al. Phenylalanine hydroxylase genotype-phenotype associations in the United States: A single center study. Mol Genet Metab 2019;128:415-21.
- Karaca M, Ozgul RK, Unal O, Yucel-Yilmaz D, Kilic M, Hismi B, et al. Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. Eur J Pediatr 2015;174:1077-84.
- Canda E, Kalkan Ucar S, Coker M. Biotinidase Deficiency: Prevalence, Impact And Management Strategies. Pediatric Health Med Ther 2020;11:127-33.
- Funghini S, Tonin R, Malvagia S, Caciotti A, Donati MA, Morrone A, et al. High frequency of biotinidase deficiency in Italian population identified by newborn screening. Mol Genet Metab Rep 2020;25:100689.
- El-Metwally A, Yousef Al-Ahaidib L, Ayman Sunqurah A, Al-Surimi K, Househ M, Alshehri A, et al. The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review. Biomed Res Int 2018;2018:7697210.
- Akova İ, Kılıç E, Koşaroğlu NE. Evaluation of the results of the 10-year screening program for neonatal metabolic and endocrine diseases: The case of Sivas province, Türkiye. Turk J Public Health 2022; 20:410-22.
- Toktas I, Saribas S, Canpolat S, Erdem O, Ozbek MN. Evaluation of patients diagnosed with phenylketonuria and biotinidase deficiency by the newborn screening program: a ten-year retrospective study. Turk J Pediatr 2022;64:985-92.
- Camp KM, Parisi MA, Acosta PB, Berry GT, Bilder DA, Blau N, et al. Phenylketonuria Scientific Review Conference: state of the science and future research needs. Mol Genet Metab 2014;112:87-122.
- Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med 2014;16:188-200.
- Surucu Kara I, Kose E, Koc Yekeduz M, Eminoglu FT. A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity. J Pediatr Endocrinol Metab 2023;36:1061-71.
- Tezel B, Aydın Ş. Infant Mortality Situation Report in Turkey on the 100th Anniversary of the Establishment of the Ministry of Health. Ankara: Turkish Republic of Ministry of Health, General Directorate of Public Health, 2021.
- Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet Metab 2010;100:6-13.
- Porta F, Pagliardini V, Celestino I, Pavanello E, Pagliardini S, Guardamagna O, et al. Neonatal screening for biotinidase deficiency: A 30-year single center experience. Mol Genet Metab Rep 2017;13:80-2.
- Mohamed S, Elsheikh W, Al-Aqeel AI, Alhashem AM, Alodaib A, Alahaideb L, et al. Incidence of newborn screening disorders among 56632 infants in Central Saudi Arabia. A 6-year study. Saudi Med J 2020;41:703-8.
- Zeybek AC, Kiykim E, Zubarioglu T, Cansever MS, Ceylaner S, Erkan T. Citrin Deficiency: An Infant Incidentally Detected by Phenylketonuria Screening with a Novel Mutation in Slc25a13 Gene. Genet Couns 2015;26:409-13.
- Unal O, Ozturk-Hismi B, Coskun T, Tokatli A, Dursun A, Sivri HS. Detection of other inborn errors of metabolism in hyperphenylalaninemic babies picked up on narrow-spectrum screening programs. Turk J Pediatr 2012;54:409-12.
- Sondhi V, Sharma S. Vitamin-Responsive Movement Disorders in Children. Ann Indian Acad Neurol 2020;23:325-31.
- Ferreira P, Chan A, Wolf B. Irreversibility of Symptoms with Biotin Therapy in an Adult with Profound Biotinidase Deficiency. JIMD Rep 2017;36:117-20.
- Wolf B. High doses of biotin can interfere with immunoassays that use biotin-strept(avidin) technologies: Implications for individuals with biotin-responsive inherited metabolic disorders. Mol Genet Metab 2019;127:321-4.
Diagnosis and Treatment of Newborns Referred to the Metabolism Department From the National Newborn Screening Program in Türkiye: A 5-Year Single-Center Experience
Abstract
Objective: The aims of this study were to investigate biochemical and genetic tests and treatment plans of newborns referred to our center with inherited metabolic disorders screened in Türkiye National Newborn Screening Program (NNSP).
Material and Methods: The medical records of babies referred by the NNSP between January 2019 and November 2023 were scanned retrospectively. Plasma biotinidase activity and the biotinidase gene (BTD) analysis results for suspected biotinidase deficiency (BD), the plasma phenylalanine and phenylalanine hydroxylase gene (PAH) analysis for a suspicion of phenylketonuria (PKU) were documented with treatment information.
Results: A total of 143 babies, 78 (54.5%) with suspected BD and 65 (45.5%) with suspected PKU were included. A PAH gene analysis was performed on 23 (35.4%) of those had high plasma phenylalanine levels, among which 86.9% were identified with the biallelic variant. Five patients were started on sapropterin-diet combined therapy, three on diet therapy and one on sapropterin therapy. In the first serum biotinidase activity measurement of babies referred with suspected BD, a heterozygous deficiency was detected in 48.7%, partial deficiency in 39.7% and profound deficiency in 10.3%. A BTD gene analysis was performed on 79.5% of those with suspected BD, and biallelic variants were detected in 50%. Forty-six patients (59.0%) underwent biotin treatment.
Conclusion: In our study, approximately one-third of the babies referred from NNSP over the five-year course of the study had biallelic variants of the relevant disease. Our research is one of the few studies on NNSP in our country and presents the diagnosis and treatment process of PKU and BD.
References
- Kaplan S, Pinar G, Kaplan B, Aslantekin F, Karabulut E, Ayar B, et al. The Prevalence of Consanguineous Marriages and Affecting Factors in Turkey: A National Survey. J Biosoc Sci 2016;48:616-30.
- https://hsgm.saglik.gov.tr/tr/tarama-programlari/ntp.html. Access Date: January 20, 2024
- Tezel B, Dilli D, Bolat H, Sahman H, Ozbas S, Acican D, et al. The development and organization of newborn screening programs in Turkey. J Clin Lab Anal. 2014;28:63-9.
- Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, et al. The Genetic Landscape and Epidemiology of Phenylketonuria. Am J Hum Genet. 2020;107:234-50.
- Rajabi F, Rohr F, Wessel A, Martell L, Dobrowolski SF, Guldberg P, et al. Phenylalanine hydroxylase genotype-phenotype associations in the United States: A single center study. Mol Genet Metab 2019;128:415-21.
- Karaca M, Ozgul RK, Unal O, Yucel-Yilmaz D, Kilic M, Hismi B, et al. Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening. Eur J Pediatr 2015;174:1077-84.
- Canda E, Kalkan Ucar S, Coker M. Biotinidase Deficiency: Prevalence, Impact And Management Strategies. Pediatric Health Med Ther 2020;11:127-33.
- Funghini S, Tonin R, Malvagia S, Caciotti A, Donati MA, Morrone A, et al. High frequency of biotinidase deficiency in Italian population identified by newborn screening. Mol Genet Metab Rep 2020;25:100689.
- El-Metwally A, Yousef Al-Ahaidib L, Ayman Sunqurah A, Al-Surimi K, Househ M, Alshehri A, et al. The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review. Biomed Res Int 2018;2018:7697210.
- Akova İ, Kılıç E, Koşaroğlu NE. Evaluation of the results of the 10-year screening program for neonatal metabolic and endocrine diseases: The case of Sivas province, Türkiye. Turk J Public Health 2022; 20:410-22.
- Toktas I, Saribas S, Canpolat S, Erdem O, Ozbek MN. Evaluation of patients diagnosed with phenylketonuria and biotinidase deficiency by the newborn screening program: a ten-year retrospective study. Turk J Pediatr 2022;64:985-92.
- Camp KM, Parisi MA, Acosta PB, Berry GT, Bilder DA, Blau N, et al. Phenylketonuria Scientific Review Conference: state of the science and future research needs. Mol Genet Metab 2014;112:87-122.
- Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med 2014;16:188-200.
- Surucu Kara I, Kose E, Koc Yekeduz M, Eminoglu FT. A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity. J Pediatr Endocrinol Metab 2023;36:1061-71.
- Tezel B, Aydın Ş. Infant Mortality Situation Report in Turkey on the 100th Anniversary of the Establishment of the Ministry of Health. Ankara: Turkish Republic of Ministry of Health, General Directorate of Public Health, 2021.
- Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet Metab 2010;100:6-13.
- Porta F, Pagliardini V, Celestino I, Pavanello E, Pagliardini S, Guardamagna O, et al. Neonatal screening for biotinidase deficiency: A 30-year single center experience. Mol Genet Metab Rep 2017;13:80-2.
- Mohamed S, Elsheikh W, Al-Aqeel AI, Alhashem AM, Alodaib A, Alahaideb L, et al. Incidence of newborn screening disorders among 56632 infants in Central Saudi Arabia. A 6-year study. Saudi Med J 2020;41:703-8.
- Zeybek AC, Kiykim E, Zubarioglu T, Cansever MS, Ceylaner S, Erkan T. Citrin Deficiency: An Infant Incidentally Detected by Phenylketonuria Screening with a Novel Mutation in Slc25a13 Gene. Genet Couns 2015;26:409-13.
- Unal O, Ozturk-Hismi B, Coskun T, Tokatli A, Dursun A, Sivri HS. Detection of other inborn errors of metabolism in hyperphenylalaninemic babies picked up on narrow-spectrum screening programs. Turk J Pediatr 2012;54:409-12.
- Sondhi V, Sharma S. Vitamin-Responsive Movement Disorders in Children. Ann Indian Acad Neurol 2020;23:325-31.
- Ferreira P, Chan A, Wolf B. Irreversibility of Symptoms with Biotin Therapy in an Adult with Profound Biotinidase Deficiency. JIMD Rep 2017;36:117-20.
- Wolf B. High doses of biotin can interfere with immunoassays that use biotin-strept(avidin) technologies: Implications for individuals with biotin-responsive inherited metabolic disorders. Mol Genet Metab 2019;127:321-4.
Details
| Primary Language | English |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Early Pub Date | May 10, 2024 |
| Publication Date | |
| Submission Date | March 17, 2024 |
| Acceptance Date | April 15, 2024 |
| Published in Issue | Year 2024 Articles Online First |
The publication language of Turkish Journal of Pediatric Disease is English.
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