Infantile Nephropathic Cystinosis in Sulaimani Pediatric Teaching Hospital: A Retrospective Cohort Study

Abstract = 941 times | PDF = 115 times

Main Article Content

Hunar Jamal Hussein Khalid Hama Salih Adnan Mohammed Hasan

Abstract

Cystinosis is a rare metabolic autosomal recessive disorder which characterized by intralysosomal accumulation of cystine. There are three forms; infantile nephropathic is the commonest forms. to evaluate clinical presentations and outcome of infantile cystinosis. A retrospective cohort study conducted in Sulaimani Pediatric Teaching Hospital on 25 patients with infantile cystinosis during May 1, 2014, to June 1, 2017. This study has depended on clinical symptoms and signs, and corneal crystallization for the diagnosis of cystinosis. Gender of the patients was 13 (52%) females and 12 (48%) males. The ages were ranged between (1-12 years) with a mean age of (6.25 years). Eight (32%) patients were from Sulaimani city, but the other 17 (68%) patients were from outside of Sulaimani. Moreover, a 17 (68%) of them were Arabic and the other eight (32%) were Kurdish ethnic groups. The study showed a 20 (80%) positive consanguinity with 19 (76%) positive family history of infantile cystinosis. Additionally, the age of first presentations was between (0.25-2 years) with a mean of (0.8 years). Clinical features included a 100% for polyuria, polydipsia, and failure to thrive. Furthermore, 10 (40%) presented with constipation, 23 (92%) photophobia and 5 (20%) blond hair. Complications included 24 (96%) rickets, 14 (56%) renal insufficiency, 5 (20%) hypothyroidism, 4 (16%) genu valgum, 3 (12%) growth hormone deficiency, and 3 (12%) developed end-stage renal disease. Subsequently, two patients died (8%) due to end-stage renal disease. Finally, there was a statistically significant relationship between both renal insufficiency (P-value = 0.042) and hypothyroidism (P-value < 0.001) with Kurdish ethnicity. Conclusion: Incidence of cystinosis was high among consanguineous parents and those patients who had a positive family history of cystinosis. Furthermore, the delay in diagnosis was due to atypical presentations and unavailability of specific investigations.

Keywords

infantile cystinosis, clinical presentations, consanguinity, family history.

Downloads

Download data is not yet available.

Article Details

References

[1] W. A. Gahl, J. G. Thoene, J. A. Schneider. "Cystinosis". N Engl J Med, Vol.347, PP.111-121, 2002.
[2] G. Nesterova , W. A. Gahl. "Cystinosis: the evolution of a treatable disease". Pediatr Nephrol. Vol. 28, PP. 51-59, 2013. doi:10.1007/s00467-012-2242-5.
[3] E. Levtchenko, L. van den Heuvel, F. Emma et al. "Clinical utility gene card for: cystinosis". Eur J Hum Genet., Vol. 22, PP. e1-e3, 2014. doi:10.1038/ejhg.2013.204
[4] M. Town, G. Jean, S. Cherqui et al. "A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis". Nat Genet, Vol. 18, PP. 319-324, 1998.
[5] G. Nesterova, W. Gahl. "Nephropathic cystinosis: late complications of a multisystemic disease". Pediatr Nephrol, Vol. 23(6), PP. 863-878, Jun. 2008. doi: 10.1007/s00467-007-0650-8
[6] A. C. Hutchesson, S. Bundey, M. A. Preece et al. "A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands, UK”. J Med Genet, Vol. 35, PP. 366–370, 1998.
[7] M. Greco, M. Brugnara, M. Zaffanello et al. "Long-term outcome of nephropathic cystinosis: a 20-year single-center experience". Pediatr Nephrol. Vol. 25, PP. 2459–2467, 2010. doi: 10.1007/s00467-010-1641-8
[8] E. Tsilou, M. Zhou, W. Gahl et al. "Ophthalmic manifestations and histopathology of infantile nephropathic cystinosis: report of a case and review of the literature". Surv Ophthalmol, Vol. 52, PP. 97-105, 2007. doi: 10.1016/j.survophthal.2006.10.006
[9] W. A. Gahl, E. M. Kuehl, F. Iwata et al. "Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops". Mol Genet Metab. Vol. 71, PP. 100–120. 2000. doi: https://doi.org/10.1006/mgme.2000.3062
[10] J. J. Robert, M. J. Tête, G. Guest et al. "Diabetes mellitus in patients with infantile cystinosis after renal transplantation". Pediatr Nephrol, Vol. 13, PP. 524–529, 1999. doi: https://doi.org/10.1007/s004670050651
[11] S. Bava, R. J. Theilmann, M Sach et al. "Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage". Cortex, Vol. 46, PP. 206–216, 2010. doi: https://doi.org/10.1016/j.cortex.2009.03.008
[12] M. Broyer, M. J. Tete, G. Guest et al. "Clinical polymorphism of cystinosis encephalopathy. Results of treatment with cysteamine". J Inherit Metab Dis, Vol. 19, PP. 65–75, 1996. doi: https://doi.org/10.1007/BF01799350
[13] G. Guillet, B. Sassolas, S. Fromentoux et al. "Skin storage of cystine and premature skin ageing in cystinosis". Lancet, Vol. 352, PP. 1444-1445, 1998. doi: http://dx.doi.org/10.1016/S0140-6736(05)61267-6
[14] M. Besouw, E. Levtchenko. "Growth retardation in children with cystinosis". Minerva Pediatr, Vol. 62, PP. 307e14, Jun. 2010.
[15] K. J. V. Stralen, F. Emma, K. J. Jager et al. "Improvement in the renal prognosis in nephropathic cystinosis". Clin J Am Soc Nephrol. Vol. 6, PP. 2485–2491. 2011. doi: 10.2215/CJN.02000311.
[16] R. G. Oshima, R. C. Willis, C. E. Furlong et al. "Binding assays for amino acids. The utilization of a cystine binding protein from Escherichia coli for the determination of acid-soluble cystine in small physiological samples". J Biol Chem, Vol. 249, PP. 6033-6039, 1974.
[17] N. F. A.Azat. "Natural History of Symptomatically Treated Children with Cystinosis". The Iraqi Postgraduate Medical Journal, Vol.11, PP. 253-257, 2012.
[18] M. J. Wilmer, J. P. Schoeber, L. P. van den Heuvel et al. "Cystinosis: practical tools for diagnosis and treatment". Pediatr Nephrol. Vol. 26, PP. 205–215, Feb. 2011. doi: 10.1007/s00467-010-1627-6
[19] M. Jackson, E. Young. "Prenatal diagnosis of cystinosis by quantitative measurement of cystine in chorionic villi and cultured cells". Prenat Diagn, Vol. 25, PP. 1045–1047, Nov. 2005. doi: 10.1002/pd.1249
[20] G. Nesterova, W. Gahl. "Cystinosis: the evolution of a treatable disease". Pediatr Nephrol, Vol. 28, PP. 51–59, Jan. 2013. doi: 10.1007/s00467-012-2242-5
[21] S. Cherqui. "Cysteamine therapy: a treatment for cystinosis, not a cure". Kidney Int, Vol. 81, PP. 127–129, 2012. doi: 10.1038/ki.2011.301
[22] J. G. Thoene. "A review of the role of enhanced apoptosis in the pathophysiology of cystinosis". Mol Genet Metab, Vol. 92, PP. 292–298, 2007.
[23] S. Nakhaii, N. Hooman, H. Otoukesh. "Gastrointestinal Manifestations of Nephropathic Cystinosis in Children". Iran J Kidney Dis, Vol. 3, PP. 218-221, Oct. 2009.
[24] M. Doğan, K. Bulan, S. Kaba et al. "Cystinosis in Eastern Turkey". J Pediatr Endocrinol Metab, Vol. 1;29, PP. 965-969, Aug. 2016. doi: 10.1515/jpem-2014-0477
[25] S. Shahkarami , H. Galehdari, A. Ahmadzadeh et al. "The first Molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran". Nefrología, Vol. 33, PP. 308-315, 2013. doi: 10.3265/Nefrologia.pre2012.Sep.11558
[26] A. Bertholet-Thomas, J. Berthiller, V. Tasic et al. "Worldwide view of nephropathic cystinosis: results from a survey from 30 countries". BMC Nephrol, Vol. 18, PP. 210, Jul. 2017. doi: 10.1186/s12882-017-0633-3
[27] M. Greco, M. Brugnara, M. Zaffanello et al. "Long-term outcome of nephropathic cystinosis: a 20-year single-center experience". Pediatr Nephrol, Vol. 25, PP. 2459–2467, 2010.doi: 10.1007/s00467-010-1641-8
[28] C. Chiaverini, L. Sillard, E. Flori, S. Ito, S. Briganti, K. Wakamatsu et al. "Cystinosis is a melanosomal protein that regulates melanin synthesis". FASEB journal, Vol. 26, PP. 3779-3789, 2012. doi: fj.11-201376v1 26/9/3779
[29] G. Guillet, B. Sassolas, S. Fromentoux et al. "Skin storage of cystine and premature skin ageing in cystinosis". Lancet, Vol. 352, PP. 1444-1445, Oct. 1988. doi: https://doi.org/10.1016/S0140-6736(05)61267-6
[30] J. Bacchetta, M. Greco, A. Bertholet-Thomas et al. "Skeletal implications and management of cystinosis: three case reports and Literature review". Bonekey Rep, Vol. 5, PP. 828, Aug. 2016. doi: 10.1038/bonekey.2016.55.
[31] M Besouw. "Bone problems in patients with cystinosis". 47th annual meeting of the eauropian society for pediatric nephrology (ESPN), Porto, Portugal, 2014.
[32] A. Conforti, A. Taranta, S. Biagini et al. "Cysteamine treatment restores the in vitro ability to differentiate along the osteoblastic lineage of mesenchymal stromal cells isolated from bone marrow of a cystinotic patient". J Transl Med. Vol. 13, PP. 143, May 2015. doi: 10.1186/s12967-015-0494-0
[33] M. T. P. Besouw, M. V. Dyck, I. Francois et al. "Detailed studies of growth hormone secretion in cystinosis patients". Pediatr Nephrol, Vol. 27, PP. 2123-2127. doi: 10.1007/s00467-012-2213-x
[34] D. S. Theodoropoulos, T. H. Shawker, C. Heinrichs et al. "Medullary nephrocalcinosis in nephropathic cystinosis". Pediatr Nephrol, Vol. 9, PP. 412–418, Aug. 1995.
[35] J.-J. Robert, M.-J. Tete, G. Guest et al. "Diabetus mellitus in patients with infantile cystinosis after renal transplantation". Pediatric nephrology, Vol. 13, PP. 524-529, Jul. 1999. doi: https://doi.org/10.1007/s004670050651
[36] F. Emma, G. Nesterova, C. Langman et al. "Nephropathic cystinosis: an international consensus document". Nephrol Dial Transplant. Vol. 29, PP. 87-94. 2014. http://ndt.oxfordjournals.org/content/29/suppl_4/iv87