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.
