Zellweger Sendromunda Ultrasonografi: Erken Bulgular

Year 2023, Volume: 11 Issue: 3, 142 - 148, 15.10.2023

Çiğdem Öztunalı Merve Yazol

Abstract

Amaç: Serebrohepatorenal sendrom olarak da bilinen Zellweger sendromu (ZS), çoklu organ sistemlerini etkileyen nadir ve ciddi bir peroksizomal biyogenez bozukluğudur. Etkilenen kişiler çoğunlukla yenidoğan veya erken çocukluk döneminde semptomatiktir. Yatak başı ultrasonografi (US), yenidoğan ve süt çocuklarında abdomen ve serebrumun birlikte görüntülenmesini sağlayan güvenli ve tekrarlanabilir bir yöntemdir. Bu çalışmada, ZS'li bir çocuk popülasyonunda serebrum ve abdomenin yatak başı US incelemelerindeki erken dönemdeki bulgular spektrumunu araştırmayı amaçlandı.
Gereç ve Yöntem: ZS sendromu tanısı alan dokuz çocuğun serebrum ve abdomen US görüntüleri, anormal bulguların özelliklerini ve sıklığını belirlemek amacıyla retrospektif olarak analiz edildi.
Bulgular: Serebrum ultrasonlarında en sık görülen bulgu subependimal germinolitik kistler idi. Hafif- orta dereceli ventriküler genişleme, lentikülostriat vaskülopati ve korpus kallosumun incelmesi diğer ilişkili bulgular arasındaydı. Böbreklerde kortikal ekojenitenin arttığı ve tüm hastalarda medüller hipoekojenitenin korunduğu görüldü; 9 hastanın 8'inde subkapsüler kistler, 7'sinde ise küçük ve düzensiz medullalar mevcuttu. Dört hastada artmış periportal ekojenite, safra kesesi ödemi ve safra çamuru tespit edildi. Bir hastada daha önce ZS'de bildirilmemiş kistik pankreas lezyonu vardı.
Sonuç: ZS'nin serebral bulguları manyetik rezonans görüntülemede iyi tanımlanmıştır, ancak bu sendromda serebrum ve abdomenin kombine ultrasonografik bulguları nadiren bildirilmektedir. Güvenli, kolay ulaşılabilir ve tekrarlanabilir bir görüntüleme yöntemi olarak yatak başı US, yenidoğanlarda ve bebeklerde ZS'nin çoklu sistem bulgularını saptamada kullanılabilir.

Keywords

Peroksizomal hastalıklar, Ultrasonografi, Zellweger sendromu

Ultrasonography in Zellweger Syndrome: Spectrum of Early Findings

Abstract

Aim: Zellweger syndrome (ZS), also known as cerebrohepatorenal syndrome, is a rare and severe peroxisomal biogenesis disorder that involves multiple organ systems. The affected subjects are mostly symptomatic in the neonatal or early infantile period. Bedside ultrasonography (US) is a safe and repeatable method that allows combined imaging of the abdomen and head in neonates and infants. This study aimed to investigate the spectrum of early abnormalities in bedside US examinations of the head and abdomen in a population of children with ZS.
Materials and Methods: US images of the head and abdomen in nine children diagnosed with ZS syndrome were analyzed retrospectively to identify the characteristics and frequencies of abnormal findings.
Results: Subependymal germinolytic cysts were the most frequent finding in head USs. Mild-to-moderate ventricular dilation, lenticulostriate vasculopathy, and thinning of the corpus callosum were among the associated findings. The kidneys showed increased cortical echogenicity and preservation of the medullar hypoechogenicity in all; 8 out of 9 patients had subcapsular cysts and 7 had small and irregular medullae. Increased periportal echogenicity, gallbladder edema, and biliary sludge were identified in 4 patients. One patient had a cystic pancreatic lesion that had not been previously reported in ZS.
Conclusion: The cerebral findings of ZS are well-defined in magnetic resonance imaging, however, combined ultrasonographic findings of the cerebrum and abdomen in this syndrome are rarely reported. As a safe, readily available, and repeatable imaging method, bedside US can be used in neonates and infants to identify the multisystem findings of ZS.

Keywords

Peroxisomal disorders, Ultrasonography, Zellweger syndrome

References

• 1. Klouwer FCC, Berendse K, Ferdinandusse S, Wanders RA, Engelen M, Poll-The BT. Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis. 2015;10:151. doi: 10.1186/s13023-015-0368-9.
• 2. Barkovich AJ, Peck WW. MR of Zellweger syndrome. AJNR Am J Neuroradiol. 1997 Jun-Jul;18(6):1163-70.
• 3. Nasrallah F, Zidi W, Feki M, Kacem S, Tebib N, Kaabachi N. Biochemical and clinical profiles of 52 Tunisian patients affected by Zellweger syndrome. Pediatr Neonatol. 2017;58(6):484-489. doi: 10.1016/j.pedneo.2016.08.011.
• 4. Pfeifer CM, Martinot CA. Zellweger syndrome: Depiction of MRI findings in early infancy at 3.0 Tesla. Neuroradiol J. 2017;30(5):442-444. doi: 10.1177/1971400917700670.
• 5. Luisiri A, Sotelo-Avila C, Silberstein MJ, Graviss ER. Sonography of the Zellweger syndrome. J Ultrasound Med. 1988;7(3):169-73. doi: 10.7863/jum.1988.7.3.169.
• 6. Smitthimedhin A, Otero HJ. Scimitar-like ossification of patellae led to diagnosis of Zellweger syndrome in newborn: a case report. Clin Imaging. 2018;49:128-130. doi: 10.1016/j.clinimag.2018.01.008.
• 7. Guillerman RP. Infant craniospinal ultrasonography: beyond hemorrhage and hydrocephalus. Semin Ultrasound CT MR. 2010;31(2):71-85. doi: 10.1053/j.sult.2010.01.006.
• 8. Leijser LM, de Vries LS, Rutherford MA, et al. Cranial ultrasound in metabolic disorders presenting in the neonatal period: characteristic features and comparison with MR imaging. AJNR Am J Neuroradiol. 2007;28(7):1223-31. doi: 10.3174/ajnr.A0553.
• 9. Mochel F, Grébille AG, Benachi A, et al. Contribution of fetal MR imaging in the prenatal diagnosis of Zellweger syndrome. AJNR Am J Neuroradiol. 2006 Feb;27(2):333-6.
• 10. Jain-Ghai S, Mishra N, Hahn C, Blaser S, Mercimek-Mahmutoglu S. Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine dependent epilepsy patient. Pediatrics. 2014;133(4):e1092-6. doi: 10.1542/peds.2013-1230.
• 11. Rohrbach M, Chitayat D, Maegawa G, et al. Intracerebral periventricular pseudocysts in a fetus with mitochondrial depletion syndrome: an association or coincidence. Fetal Diagn Ther. 2009;25(2):177-82. doi: 10.1159/000209385.
• 12. Schlesinger AE, Shackelford GD, Adcock LM. Hyperechoic caudate nuclei: a potential mimic of germinal matrix hemorrhage. Pediatr Radiol. 1998;28(5):297-302. doi: 10.1007/s002470050357.
• 13. Salas J, Tekes A, Hwang M, Northington FJ, Huisman TAGM. Head Ultrasound in Neonatal Hypoxic-Ischemic Injury and Its Mimickers for Clinicians: A Review of the Patterns of Injury and the Evolution of Findings Over Time. Neonatology. 2018;114(3):185-197. doi: 10.1159/000487913.
• 14. Sarnat HB, Trevenen CL, Darwish HZ. Ependymal abnormalities in cerebro-hepato-renal disease of Zellweger. Brain Dev. 1993;15(4):270-7. doi: 10.1016/0387-7604(93)90022-z.
• 15. Malinescu B, Martius E, Pelin AM. Violent death in a rare peroxisomal disease--Zellweger syndrome. Forensic Sci Int. 2015 Oct;255:89-95. doi: 10.1016/j.forsciint.2015.07.009.
• 16. Szpecht D, Frydryszak D, Miszczyk N, Szymankiewicz M, Gadzinowski J. The incidence of severe intraventricular hemorrhage based on retrospective analysis of 35939 full-term newborns-report of two cases and review of literature. Childs Nerv Syst. 2016;32(12):2447-2451. doi: 10.1007/s00381-016-3164-5.
• 17. Takenouchi T, Praveen Raju G. Germinal matrix hemorrhage in Zellweger syndrome. J Child Neurol. 2010;25(11):1398-400. doi: 10.1177/0883073810365545.
• 18. Quintas-Neves M, Carvalho R, Soares-Fernandes JP. Brain MRI in a newborn with Zellweger syndrome: ADC quantitation in white matter disease. Childs Nerv Syst. 2018 Jun;34(6):1103-1104. doi: 10.1007/s00381-018-3791-0.
• 19. van der Knaap MS, Wassmer E, et al. MRI as diagnostic tool in early-onset peroxisomal disorders. Neurology. 2012 Apr 24;78(17):1304-8. doi: 10.1212/WNL.0b013e31825182dc.
• 20. Nissenkorn A, Michelson M, Ben-Zeev B, Lerman-Sagie T. Inborn errors of metabolism: a cause of abnormal brain development. Neurology. 2001;56(10):1265-72. doi: 10.1212/wnl.56.10.1265.
• 21. Baes M, P Van Veldhoven P. Hepatic dysfunction in peroxisomal disorders. Biochim Biophys Acta. 2016 May;1863(5):956-70. doi: 10.1016/j.bbamcr.2015.09.035.
• 22. Berendse K, Koot BGP, Klouwer FCC, et al. Hepatic symptoms and histology in 13 patients with a Zellweger spectrum disorder. J Inherit Metab Dis. 2019 Sep;42(5):955-965. doi: 10.1002/jimd.12132.
• 23. Avni FE, Garel C, Cassart M, D'Haene N, Hall M, Riccabona M. Imaging and classification of congenital cystic renal diseases. AJR Am J Roentgenol. 2012;198(5):1004-13. doi: 10.2214/AJR.11.8083.
• 24. Thomas CC, Jana M, Sinha A, et al. Ultrasound Imaging of Renal Cysts in Children. J Ultrasound Med. 2021;40(3):621-635. doi: 10.1002/jum.15435.
• 25. Ferro F, Vezzali N, Comploj E, et al. Pediatric cystic diseases of the kidney. J Ultrasound. 2019 Sep;22(3):381-393. doi: 10.1007/s40477-018-0347-9.
• 26. Distelmaier F, Vogel M, Spiekerkötter U, et al. Cystic renal dysplasia as a leading sign of inherited metabolic disease. Pediatr Nephrol. Dec;22(12):2119-24. doi: 10.1007/s00467-007-0536-9.
• 27. Breitling R. Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitör. BMC Pediatr. 2004;4:5. doi: 10.1186/1471-2431-4-5.
• 28. van Konijnenburg EMMH, Luirink IK, Schagen SEE, et al. Hyperinsulinism in a patient with a Zellweger Spectrum Disorder and a 16p11.2 deletion syndrome. Mol Genet Metab Rep.2020;23:100590. doi: 10.1016/j.ymgmr.2020.100590.