Nadir Multisistemik ve Zor Tanı Alan Doğumsal Metabolik Hastalıklara Örnek Olarak Peroksizomal Hastalıklar
Abstract
Amaç: Peroksizomal hastalıklar (PH’lar), otozomal resesif geçiş gösteren ve birçok farklı klinik şekilde ortaya çıkabilen doğumsal hastalıklardır. Bu çalışmada, kliniğimizde tanı alan ve izlenen PH tanısı almış olan olguların klinik ve laboratuvar bulgularının ve moleküler genetik özelliklerinin geriye dönük olarak incelenmesi planlanmıştır.
Gereç ve Yöntemler: Bu çalışma Dr. Sami Ulus Kadın Doğum, Çocuk Sağlığı ve Hastalıkları Eğitim ve Araştırma Hastanesi, çocuk metabolizma bölümünde gerçekleştirildi. Ocak 2020 ile Aralık 2020 tarihlerinde, PH şüphesiyle çok uzun zincirli yağ asitleri (ÇUZYA) analizi yapılmış olan hastaların verileri derlendi. 1 yıl içerisinde çeşitli gerekçelerle ÇUZYA analiz edilmiş olan hastalardan, 71 tanesinde anormal değerler tesbit edilmişti. Bu hastaların 20 tanesinde moleküler genetik analiz yöntemleri ile PH’lar araştırılmış ve 6 hastada tesbit edilmişti. Pozitif sonuç elde edilen hastaların verileri hasta dosyalarından derlendi.
Bulgular: Altı hastanın verileri geriye yönelik olarak incelendi. Hastaların tanıları şu şekildeydi: Zellweger sendromu (3 hasta), Rizomelik kondrodisplazi punktata tip 1 (2 hasta), AMACR eksikliği (1 hasta). Hastaların başvuru yaşları yenidoğan dönemi ve 6 yaş arasında değişmekteydi. Başlıca başvuru semptomları hipotoni, gelişme geriliği beslenme güçlüğü ve dismorfik yüz bulgularıydı. Tüm hastalarda multisistemik tutulum tesbit edildi. Hastaların laboratuvar incelemelerinde transaminaz yüksekliği en sık saptanan patolojik bulguydu. Bütün hastaların ÇUZYA analizinde yüksek değerler tesbit edildi. Hastaların hepsinde altta yatan genetik patoloji moleküler genetik analiz yöntemleri ile gösterildi (PEX1, PEX5, PEX6, PEX7, PEX12, PEX 26 ve AMACR genleri). Zellweger sendromu tanılı iki hastaya kolik asit tedavisi uygulandı.
Sonuç: PH’lar nadir görülen ve farklı klinik bulgularla seyredebilen doğumsal metabolik hastalıklardır. Her ne kadar PH’ın kesin tanısında genetik panel analizleri kullanılsa da, ÇUZYA analizi tanı için yönlendirici olan kolay ve hızlı bir tanısal testtir. Bu nedenle, özellikle görme ve işitme bozukluğu, karaciğer patolojisi ve dismorfik bulguları olan hastalarda tarama programlarına eklenmelidir.
Keywords
Peroksizomal biyogenez bozuklukları PEX geni Peroksizomal enzim eksiklikleri Çok uzun zincirli yağ asitleri analizi Zellweger spectrum bozuklukları
References
- 1) Braverman NE, D’Agostino MD, Maclean GE. Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Dev Disabil Res Rev 2013;17:187–96.
- 2) Waterham HR, Ferdinandusse S, Wanders RJ. Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta.2016 ;1863 :922-33.
- 3) Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT. Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis 2015;10:151.
- 4) Steinberg, SJ.; Raymond, GV.; Braverman, NE.; Moser, AB. Peroxisome biogenesis disorders, Zellweger syndrome spectrum. In: Pagon, RA.; Adam, MP.;Ardinger, HH., et al., editors. GeneReviews® [Internet]. University of Washington; Seattle, Seattle (WA): Dec 12. 2003 (1993– 2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1448/, Updated 2012 May 10)
- 5) Gould S, Raymond G, Valle D. The peroxisome biogenesis diosorders. In: The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, 2001; 3181–218
- 6) Keane MH, Overmars H, Wikander TM, Ferdinandusse S, Duran M, Wanders RJ, et al. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice. Hepatology 2007;45:982-97.
- 7) Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, et al. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum Mutat 2002;20:284-97.
- 8) Smith EH, Gavrilov DK, Oglesbee D, Freeman WD, Vavra MW, Matern D, et al. An adult onset case of alpha-methyl-acyl-CoA racemase deficiency. J Inherit Metab Dis 2010;33 Suppl 3:S349-53.
- 9) Gündüz M, Ünal Ö, Küçükçongar-Yavaş A, Kasapkara Ç. Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes. Turk J Pediatr 2019;61:289-291.
- 10) Berendse K, Klouwer FC, Koot BG, Kemper EM, Ferdinandusse S, Koelfat KV, et al. Cholic acid therapy in Zellweger spectrum disorders. J Inherit Metab Dis 2016;39:859-68.
Abstract
Objective: Peroxisomal diseases (PDs) are autosomal recessively inherited inborn errors of metabolism (IEMs) that have a wide range of clinical presentations, with variable severity. The aim of this study was to describe cases with various subtypes of PDs with different clinical presentations and to increase the awareness of pediatricians to this metabolic disorder.
Material and Methods: The study was conducted in Dr. Sami Ulus Maternity and Child Health Treatment and Research Hospital, division of pediatric metabolism, between December 2020 and January 2021. Patients of whom very long chain fatty acids (VLCFAs) were analysed due to various conditions between January 2020 and December 2020 were retrospectively evaluated. Among patients that VLCFA analyses were performed, 71 tests were found to have abnormal results and 20 of these patients had undergone molecular genetic analysis with the suspicion of PDs. An underlying genetic pathology was detected in 6 patients. Data of patients were obtained from patients files.
Results: Six patients were evaluated. Diagnoses of patients were as following: Zellweger spectrum disorders (n=4), rhisomelic chondrodysplasia punctata type 1 (n=1), and AMACR deficiency (n=1). Age of onset of clinical symptoms ranged from the neonatal period to 6 years. Main clinical symptoms were hypotonia, developmental delay and dysmorphic findings. Three patients had cataracts and 5 had sensorineural deafness. Elevated transaminases were detected in 5/6 patients, of whom 4 had abnormal liver function tests. VLCFAs were found to be elevated in all patients. Variants in PEX1, PEX5, PEX6, PEX7, PEX12, PEX 26 and AMACR genes were detected. Patients with liver insufficiency received cholic acid treatment.
Conclusion: PDs are very rare IEMs that comprise various subtypes with range of clinical phenotypes with different clinical presentations. Although genetic panel analyses is required for the diagnosis of, VLCFA analysis is a very simple and quick tool for the detection of PDs, and should be included in the screening of patients with visual and hearing impairments, liver disease and dysmorphic findings.
Keywords
Peroxisomal biogenesis disorders PEX gene Single peroxisomal enzyme deficiencies Very long chain fatty acids Zellweger spectrum disorders
References
- 1) Braverman NE, D’Agostino MD, Maclean GE. Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Dev Disabil Res Rev 2013;17:187–96.
- 2) Waterham HR, Ferdinandusse S, Wanders RJ. Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta.2016 ;1863 :922-33.
- 3) Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT. Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis 2015;10:151.
- 4) Steinberg, SJ.; Raymond, GV.; Braverman, NE.; Moser, AB. Peroxisome biogenesis disorders, Zellweger syndrome spectrum. In: Pagon, RA.; Adam, MP.;Ardinger, HH., et al., editors. GeneReviews® [Internet]. University of Washington; Seattle, Seattle (WA): Dec 12. 2003 (1993– 2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1448/, Updated 2012 May 10)
- 5) Gould S, Raymond G, Valle D. The peroxisome biogenesis diosorders. In: The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, 2001; 3181–218
- 6) Keane MH, Overmars H, Wikander TM, Ferdinandusse S, Duran M, Wanders RJ, et al. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice. Hepatology 2007;45:982-97.
- 7) Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, et al. Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum Mutat 2002;20:284-97.
- 8) Smith EH, Gavrilov DK, Oglesbee D, Freeman WD, Vavra MW, Matern D, et al. An adult onset case of alpha-methyl-acyl-CoA racemase deficiency. J Inherit Metab Dis 2010;33 Suppl 3:S349-53.
- 9) Gündüz M, Ünal Ö, Küçükçongar-Yavaş A, Kasapkara Ç. Alpha methyl acyl CoA racemase deficiency: Diagnosis with isolated elevated liver enzymes. Turk J Pediatr 2019;61:289-291.
- 10) Berendse K, Klouwer FC, Koot BG, Kemper EM, Ferdinandusse S, Koelfat KV, et al. Cholic acid therapy in Zellweger spectrum disorders. J Inherit Metab Dis 2016;39:859-68.
Details
| Primary Language | English |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Publication Date | July 16, 2021 |
| Submission Date | February 17, 2021 |
| Published in Issue | Year 2021 Volume: 15 Issue: 4 |
The publication language of Turkish Journal of Pediatric Disease is English.
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