Background: Atypical hemolytic uremic syndrome (aHUS) is a relatively rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction due to gene mutation of complement factors leading to dysregulated activation of the alternative complement pathway. Mutation of CD46 or membrane cofactor protein accounts for 5-20 percent of cases of atypical HUS. Clinical description: Here we report a 7-year-old boy with recurrent episodes of acute kidney injury and thrombocytopenia associated with diarrheal episode who was subsequently found to be having CD46 mutation. He was negative for anti-complement factor H (20AU/ml, ref 0-100 AU/ml). Renal ultrasonography showed normal kidney size with increased echogenicity. With a diagnosis of HUS with AKI and stage 1 hypertension, the patient was managed with amlodipine with monitoring of fluid and electrolyte status. The child underwent three sessions of hemodialysis. After one and half months of the episode, the patient got admitted for the third time with complaints of abdominal pain, hematuria, and oliguria. This episode was not associated with diarrhoea. His whole exome sequencing tested for mutation implicated in atypical HUS revealed a homozygous deletion (77bp) variant in Exon 14 of the CD46 gene. Patient was finally diagnosed with atypical HUS due to CD46 (MCP) mutation. Conclusion: HUS presenting in the context of a diarrhoeal episode should not always be assumed to be diarrhoea-associated HUS and in the recurrence of such episodes, screening for the genetic cause/complement mutation is crucial to establish underlying etiology and deciding therapeutic strategies.
| Published in | American Journal of Pediatrics (Volume 9, Issue 3) |
| DOI | 10.11648/j.ajp.20230903.14 |
| Page(s) | 122-125 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Atypical HUS, Acute Kidney Injury (AKI), Diarrhoea, Alternative Complement Pathway, CD 46 Mutation
| [1] | Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16: 1035. |
| [2] | Noris M, Caprioli J, Bresin E, et al. The relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5: 1844. |
| [3] | Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365: 1073–86. |
| [4] | Kavanagh D, Goodship TH, Richards A. Atypical haemolytic uremic syndrome. Semin Nephrol 2013; 33: 508–30. |
| [5] | Geerdink LM, Westra D, van Wijk JA, et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol 2012; 27: 1283. |
| [6] | Liszewski MK, Atkinson JP. Complement regulator CD46 genetic variants and disease associations. Hum Genomic 2015; 9: 7. |
| [7] | Richards A, Kathryn Liszewski M, Kavanagh D et. al. Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome. Mol Immunol 2007; 44: 111–22. |
| [8] | Vilalta R, Al-Akash S, Davin J, et al. Eculizumab therapy for pediatric patients with atypical hemolytic uremic syndrome: efficacy and safety outcomes of a retrospective study [abstract 1155]. Haematologica. 2012; 97 (suppl 1): 479. |
| [9] | Greenbaum LA, Fila M, Ardissino G, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 2016; 89: 701–11. |
| [10] | Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361: 1676. |
| [11] | Nayer A, Asif A. Atypical Hemolytic-Uremic Syndrome: A Clinical Review. Am J Ther 2016; 23 (1): e151-e158. |
| [12] | Yoshida Y, Kato H, Ikeda Y, Nangaku M. Pathogenesis of Atypical Hemolytic Uremic Syndrome. J Atheroscler Thromb 2019; 26 (2): 99-110. |
| [13] | Klämbt V, Gimpel C, Bald M, et al. Different approaches to long-term treatment of aHUS due to MCP mutations: a multicenter analysis. Pediatr Nephrol 2021; 36: 463. |
| [14] | Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 2006; 108: 1267. |
| [15] | Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007; 18: 2392. |
| [16] | Gurevich E, Landau D. Pharmacological Management of Atypical Hemolytic Uremic Syndrome in Pediatric Patients: Current and Future [published online ahead of print, 2023 Jan 13]. Paediatr Drugs 2023; 1-10. |
| [17] | Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet journal of rare diseases 2011; 6: 1-30. |
APA Style
Lipsa Priyadarshini, Subal Kumar Pradhan. (2023). Recurrent Acute Kidney Injury in a Child Due to CD46 Mutation Associated Hemolytic Uremic Syndrome: A Case Report and Review of Literature. American Journal of Pediatrics, 9(3), 122-125. https://doi.org/10.11648/j.ajp.20230903.14
ACS Style
Lipsa Priyadarshini; Subal Kumar Pradhan. Recurrent Acute Kidney Injury in a Child Due to CD46 Mutation Associated Hemolytic Uremic Syndrome: A Case Report and Review of Literature. Am. J. Pediatr. 2023, 9(3), 122-125. doi: 10.11648/j.ajp.20230903.14
AMA Style
Lipsa Priyadarshini, Subal Kumar Pradhan. Recurrent Acute Kidney Injury in a Child Due to CD46 Mutation Associated Hemolytic Uremic Syndrome: A Case Report and Review of Literature. Am J Pediatr. 2023;9(3):122-125. doi: 10.11648/j.ajp.20230903.14
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Download@article{10.11648/j.ajp.20230903.14,
author = {Lipsa Priyadarshini and Subal Kumar Pradhan},
title = {Recurrent Acute Kidney Injury in a Child Due to CD46 Mutation Associated Hemolytic Uremic Syndrome: A Case Report and Review of Literature},
journal = {American Journal of Pediatrics},
volume = {9},
number = {3},
pages = {122-125},
doi = {10.11648/j.ajp.20230903.14},
url = {https://doi.org/10.11648/j.ajp.20230903.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20230903.14},
abstract = {Background: Atypical hemolytic uremic syndrome (aHUS) is a relatively rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction due to gene mutation of complement factors leading to dysregulated activation of the alternative complement pathway. Mutation of CD46 or membrane cofactor protein accounts for 5-20 percent of cases of atypical HUS. Clinical description: Here we report a 7-year-old boy with recurrent episodes of acute kidney injury and thrombocytopenia associated with diarrheal episode who was subsequently found to be having CD46 mutation. He was negative for anti-complement factor H (20AU/ml, ref 0-100 AU/ml). Renal ultrasonography showed normal kidney size with increased echogenicity. With a diagnosis of HUS with AKI and stage 1 hypertension, the patient was managed with amlodipine with monitoring of fluid and electrolyte status. The child underwent three sessions of hemodialysis. After one and half months of the episode, the patient got admitted for the third time with complaints of abdominal pain, hematuria, and oliguria. This episode was not associated with diarrhoea. His whole exome sequencing tested for mutation implicated in atypical HUS revealed a homozygous deletion (77bp) variant in Exon 14 of the CD46 gene. Patient was finally diagnosed with atypical HUS due to CD46 (MCP) mutation. Conclusion: HUS presenting in the context of a diarrhoeal episode should not always be assumed to be diarrhoea-associated HUS and in the recurrence of such episodes, screening for the genetic cause/complement mutation is crucial to establish underlying etiology and deciding therapeutic strategies.},
year = {2023}
}
TY - JOUR T1 - Recurrent Acute Kidney Injury in a Child Due to CD46 Mutation Associated Hemolytic Uremic Syndrome: A Case Report and Review of Literature AU - Lipsa Priyadarshini AU - Subal Kumar Pradhan Y1 - 2023/07/20 PY - 2023 N1 - https://doi.org/10.11648/j.ajp.20230903.14 DO - 10.11648/j.ajp.20230903.14 T2 - American Journal of Pediatrics JF - American Journal of Pediatrics JO - American Journal of Pediatrics SP - 122 EP - 125 PB - Science Publishing Group SN - 2472-0909 UR - https://doi.org/10.11648/j.ajp.20230903.14 AB - Background: Atypical hemolytic uremic syndrome (aHUS) is a relatively rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction due to gene mutation of complement factors leading to dysregulated activation of the alternative complement pathway. Mutation of CD46 or membrane cofactor protein accounts for 5-20 percent of cases of atypical HUS. Clinical description: Here we report a 7-year-old boy with recurrent episodes of acute kidney injury and thrombocytopenia associated with diarrheal episode who was subsequently found to be having CD46 mutation. He was negative for anti-complement factor H (20AU/ml, ref 0-100 AU/ml). Renal ultrasonography showed normal kidney size with increased echogenicity. With a diagnosis of HUS with AKI and stage 1 hypertension, the patient was managed with amlodipine with monitoring of fluid and electrolyte status. The child underwent three sessions of hemodialysis. After one and half months of the episode, the patient got admitted for the third time with complaints of abdominal pain, hematuria, and oliguria. This episode was not associated with diarrhoea. His whole exome sequencing tested for mutation implicated in atypical HUS revealed a homozygous deletion (77bp) variant in Exon 14 of the CD46 gene. Patient was finally diagnosed with atypical HUS due to CD46 (MCP) mutation. Conclusion: HUS presenting in the context of a diarrhoeal episode should not always be assumed to be diarrhoea-associated HUS and in the recurrence of such episodes, screening for the genetic cause/complement mutation is crucial to establish underlying etiology and deciding therapeutic strategies. VL - 9 IS - 3 ER -
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