Main Article Content
Objective: Cystinosis is a rare, autosomal recessive, lysosomal storage disorder characterized by cystine accumulation throughout the body, due to mutations in the gene encoding cystinosin, named CTNS. Infantile nephropathic cystinosis (INC), the most severe form of the disease and the most common cause of renal Fanconi syndrome (FS), starts with proximal tubulopathy and causes renal failure and various extra-renal manifestations over the time.
Case Presentation: The authors report a 15-month-old boy of Greek origin who presented with failure to thrive over the last 7 months and was noted to have decreased weight and short stature. The metabolic control showed normoglycemic glucosuria, significant proteinuria, and generalized aminoaciduria, suggesting FS. Sequencing analysis of the CTNS gene revealed the frameshift mutation c.516dupC in the homozygous state, confirming the diagnosis of INC. Only one compound heterozygous individual for this mutation has been reported before.
Conclusion: The index case brings out a new correlation of the c.516dupC mutation in the homozygous state with a pure INC phenotype. Alongside, it reminds clinicians to consider cystinosis in the differential diagnosis of failure to thrive or short stature.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Gahl WA, Thoene JG, Schneider JA. Cystinosis. The New England journal of medicine. 2002;347(2):111-21. DOI: https://doi.org/10.1056/NEJMra020552
Ivanova E, De Leo MG, De Matteis MA, Levtchenko E. Cystinosis: clinical presentation, pathogenesis and treatment. Pediatric endocrinology reviews : PER. 2014;12 Suppl 1:176-84.
Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatric nephrology. 2013;28(1):51-9. DOI: https://doi.org/10.1007/s00467-012-2242-5
Baumner S, Weber LT. Nephropathic Cystinosis: Symptoms, Treatment, and Perspectives of a Systemic Disease. Frontiers in pediatrics. 2018;6:58. DOI: https://doi.org/10.3389/fped.2018.00058
Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nature genetics. 1998;18(4):319-24. DOI: https://doi.org/10.1038/ng0498-319
Stenson PD, Mort M, Ball EV, Shaw K, Philips A, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. 2020. http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CTNS. Accessed 12 August 2022. DOI: https://doi.org/10.1007/s00439-020-02199-3
Mason S, Pepe G, Dall'Amico R, Tartaglia S, Casciani S, Greco M, et al. Mutational spectrum of the CTNS gene in Italy. European journal of human genetics : EJHG. 2003;11(7):503-8. DOI: https://doi.org/10.1038/sj.ejhg.5200993
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Jang W, Karapetyan K, Katz K, Liu C, Maddipatla Z, Malheiro A, McDaniel K, Ovetsky M, Riley G, Zhou G, Holmes JB, Kattman BL, Maglott DR. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res . 2018 Jan 4. PubMed PMID: 29165669. SCV000617390.1. https://www.ncbi.nlm.nih.gov/clinvar/variation/449354/. Accessed 12 August 2022.
Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet journal of rare diseases. 2016;11:47. DOI: https://doi.org/10.1186/s13023-016-0426-y
Wilmer MJ, Emma F, Levtchenko EN. The pathogenesis of cystinosis: mechanisms beyond cystine accumulation. American journal of physiology Renal physiology. 2010;299(5):F905-16. DOI: https://doi.org/10.1152/ajprenal.00318.2010
Bastug F, Nalcacioglu H, Ozaltin F, Korkmaz E, Yel S. Nephropathic Cystinosis Mimicking Bartter Syndrome: a Novel Mutation. Iranian journal of kidney diseases. 2018;12(1):61-3.
Ozkan B, Cayir A, Kosan C, Alp H. Cystinosis presenting with findings of Bartter syndrome. Journal of clinical research in pediatric endocrinology. 2011;3(2):101-4. DOI: https://doi.org/10.4274/jcrpe.v3i2.21
Topaloglu R, Gulhan B, Inozu M, Canpolat N, Yilmaz A, Noyan A, et al. The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis. Clinical journal of the American Society of Nephrology : CJASN. 2017. DOI: https://doi.org/10.2215/CJN.00180117