Kliniğimizde Üre Döngüsü Bozukluğu Nedeniyle Takipli Olan Hastaların Klinik Özelliklerinin Değerlendirilmesi
Abstract
Amaç: Üre döngüsü bozuklukları (ÜDB’leri), protein metabolizması sonucunda üretilen amonyağın hücresel atılımında
yer alan enzimlerin veya taşıyıcı moleküllerinin kalıtsal eksikliklerinden kaynaklanan doğumsal metabolik hastalıklardır. Bu
çalışmanın amacı, bölümümüzde takipli olup, ÜDB olan pediatrik yaş grubundaki hastaların klinik özelliklerini ve uzun
dönem sonuçlarını değerlendirmektir.
Gereç ve Yöntemler: Araştırmamız Eylül 2020-Mart 2021 tarihleri arasında, Dr. Sami Ulus Kadın Doğum ve Çocuk Sağlığı ve Hastalıkları
Eğitim ve Araştırma Hastanesi’nde gerçekleştirildi. ÜDB olan 16 hastada [karbamoilfosfatsentetaz I eksikliği (n=1), N-asetil glutamate sentaz
eksikliği(n=1), arginino süksinat liyaz eksikliği (n=4), argininosüksinat sentetaz eksikliği (n=4), arginaz eksikliği (n=2), ornitin transkarbamilaz
eksikliği (n=2), hiperamonyemi-hiperornitinemi-homositrülinüri sendromu (n=2)] klinik özellikler geriye yönelik olarak tarandı. Semptomlar
yaşamın 28 günü içinde ortaya çıkmış ise “neonatal başlangıçlı ÜDB” terimi, semptomlar yenidoğan döneminden sonra başladı ise “geç
başlangıçlı ÜDB” terimi kullanıldı.
Bulgular: Sekiz hasta yenidoğan döneminde akut metabolik kriz ile başvurmuştu. Neonatal başlangıçlı ÜDB’lerde temel klinik fenotip
sepsis benzeri bulguları içerirken, geç başlangıçlı ÜDB’lerde epilepsy ve mental retardasyon baskındı. Neonatal başlangıçlı ÜDB olan
hastalarda, başlangıç döneminde hiperamonyeminin daha şiddetli olduğu gözlemlendi.
Sonuç: Gelişmekte olan tedavi yöntemlerine rağmen, neonatal başlangıçlı ÜDB’lerde mortalite oranları halen yüksek olarak seyretmektedir.
Neonatal başlangıçlı ÜDB’ler genellikle akut hiperamonyemi semptomları ile kendini gösterirken, nörolojik belirtiler geç başlangıçlı ÜDB’de
sıklıkla başlangıç belirtisi olarak karşımıza çıkmaktadır. Hiperamonyemisi olan çocuk hastalarda ÜDB’lerden şüphelenilmeli ve tanıyı
aydınlatmak için metabolik incelemeler ivedilikle yapılmalıdır.
Anahtar Sözcükler: Hyperammonemia, Neonate, Urea Cycle ivedilikle yapılmalıdır.
References
- Kido J, Matsumoto S, Sugawara K, Sawada T, Nakamura K. Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review. Am J Med Genet A 2021;185:2026-36.
- Bélanger-Quintana A, Arrieta Blanco F, Barrio-Carreras D, Bergua Martínez A, Cañedo Villarroya E, García-Silva MT, et al . Recommendations for the Diagnosis and Therapeutic Management of Hyperammonaemia in Paediatric and Adult Patients. Nutrients 2022;14:2755.
- Matsumoto S, Häberle J, Kido J, Mitsubuchi H, Endo F, Nakamura K. Urea cycle disorders-update. J Hum Genet 2019;64:833-47.
- Sen K, Whitehead M, Castillo Pinto C, Caldovic L, Gropman A. Fifteen years of urea cycle disorders brain research: Looking back, looking forward. Anal Biochem 2022;636:114343.
- Stone WL, Basit H, Jaishankar GB. Urea Cycle Disorders. 2022 May 9. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. PMID: 29493985.
- Hodson V, Bubb G, Lindsley K, Uyei J, Diaz GA. Natural history of arginase 1 deficiency and the unmet needs of patients: A systematic review of case reports. JIMD Rep 2022;63:330-40.
- Dorum S, Havalı C. Urea cycle disorders clinical, laboratory and genetic features: Single center experience. MKÜ Tıp Dergisi 2022;13:74-9.
- Kido J, Matsumoto S, Häberle J, Inomata Y, Kasahara M, Sakamoto S, et al. Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan. J Inherit Metab Dis 2021;44:1311-22.
- Bachmann C. Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation. Eur J Pediatr 2003 162 :410–6.
- Nassogne MC, Heron B, Touati G, Rabier D, Saudubray JM. Urea cycle defects: management and outcome. J Inherit Metab Dis 2005, 28:407–14.
- Burgard P, Kölker S, Haege G, Lindner M, Hoffmann GF. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders--review and meta-analysis of observational studies published over more than 35 years. J Inherit Metab Dis 2016;39:219-29.
Abstract
Objective: Urea cycle disorders (UCDs) are inherited deficiencies of the enzymes or transport molecules involved in the
cellular excretion of excess ammonia produced during protein metabolism. The aim of this study was to evaluate the
clinical characteristics and long-term outcome of pediatric patients with UCDs.
Material and Methods: Our research was conducted between September 2020-March 2021 in Dr. Sami Ulus
Maternity and Child Health Training and Research Hospital. Clinical characteristics in 16 patients with UCDs [carbamoyl
phosphate synthetase I deficiency (n=1), N-acetylglutamate synthase deficiency(n=1), argininosuccinate lyase deficiency
(n=4), argininosuccinate synthetase deficiency (n=4), arginase deficiency (n=2), ornithine transcarbamylase deficiency
(n=2), hyperammonemia hyperornithinemia homocitrullinuria syndrome (n=2)] were defined. The term “neonatal-onset”
UCD was used if symptoms occurred within 28 days of life, and “late-onset” if symptoms started after the neonatal
period.
Results: Eight patients presented with acute metabolic crisis during newborn period. Core clinical phenotype in
neonatal-onset UCDs included sepsis-like findings, whereas epilepsy and mental retardation was predominant in lateonset
UCDs. For patients with neonatal-onset UCDs, hyperammonemia was more severe at the initial period.
Conclusion: Despite evolving treatment opportunities, still high mortality rates were found in neonatal-onset UCD. UCDs
should be suspected in pediatric patients with hyperammonemia and metabolic investigations should be performed
immediately to enlighten diagnosis. Neonatal-onset UCD usually present with symptoms of acute hyperammonemia, while
moresubtle neurological manifestations are frequent initial findings in the late onset UCD.
References
- Kido J, Matsumoto S, Sugawara K, Sawada T, Nakamura K. Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review. Am J Med Genet A 2021;185:2026-36.
- Bélanger-Quintana A, Arrieta Blanco F, Barrio-Carreras D, Bergua Martínez A, Cañedo Villarroya E, García-Silva MT, et al . Recommendations for the Diagnosis and Therapeutic Management of Hyperammonaemia in Paediatric and Adult Patients. Nutrients 2022;14:2755.
- Matsumoto S, Häberle J, Kido J, Mitsubuchi H, Endo F, Nakamura K. Urea cycle disorders-update. J Hum Genet 2019;64:833-47.
- Sen K, Whitehead M, Castillo Pinto C, Caldovic L, Gropman A. Fifteen years of urea cycle disorders brain research: Looking back, looking forward. Anal Biochem 2022;636:114343.
- Stone WL, Basit H, Jaishankar GB. Urea Cycle Disorders. 2022 May 9. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. PMID: 29493985.
- Hodson V, Bubb G, Lindsley K, Uyei J, Diaz GA. Natural history of arginase 1 deficiency and the unmet needs of patients: A systematic review of case reports. JIMD Rep 2022;63:330-40.
- Dorum S, Havalı C. Urea cycle disorders clinical, laboratory and genetic features: Single center experience. MKÜ Tıp Dergisi 2022;13:74-9.
- Kido J, Matsumoto S, Häberle J, Inomata Y, Kasahara M, Sakamoto S, et al. Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan. J Inherit Metab Dis 2021;44:1311-22.
- Bachmann C. Outcome and survival of 88 patients with urea cycle disorders: a retrospective evaluation. Eur J Pediatr 2003 162 :410–6.
- Nassogne MC, Heron B, Touati G, Rabier D, Saudubray JM. Urea cycle defects: management and outcome. J Inherit Metab Dis 2005, 28:407–14.
- Burgard P, Kölker S, Haege G, Lindner M, Hoffmann GF. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders--review and meta-analysis of observational studies published over more than 35 years. J Inherit Metab Dis 2016;39:219-29.
Details
| Primary Language | English |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Publication Date | March 22, 2023 |
| Submission Date | April 5, 2022 |
| Published in Issue | Year 2023 Volume: 17 Issue: 2 |
The publication language of Turkish Journal of Pediatric Disease is English.
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