Persistent microscopic haematuria in a female associated with COL4A1 gene mutation: A case report
Keywords:
HANAC syndrome, Clinical Management, Pediatrics
Abstract
Background: Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1. COL4A1 gene mutation leads to a rare, multi-system disorder characterized by abnormal brain, eyes, kidneys, and muscle blood vessels. Case Presentation: We are presenting a 7-year-old child with this rare medical condition, who presented with persistent microscopic hematuria and was diagnosed through genetic screening early in life. Although she had limited clinical presentation due to her early age, the genetic testing revealed a pathogenic mutation in the COL4A1 gene, which is a known cause of HANAC syndrome. Conclusion: COL4A1 gene mutation should be suspected in patients with unexplained persistent hematuria, especially with a strong family history of the same complaint without a clear underlying reason. Early in-life diagnosis is important for prognosis, health monitoring, and management. Key Words: HANAC syndrome; Pediatric; Clinical ManagementReferences
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8. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E et al: COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med 2007, 357(26):2687-2695.
9. Kashtan CE: Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore) 1999, 78(5):338-360.
10. Pozzi A, Zent R: Integrins in kidney disease. J Am Soc Nephrol 2013, 24(7):1034-1039.
11. Tryggvason K, Zhou J, Hostikka SL, Shows TB: Molecular genetics of Alport syndrome. Kidney Int 1993, 43(1):38-44.
12. Van Agtmael T, Bruckner-Tuderman L: Basement membranes and human disease. Cell Tissue Res 2010, 339(1):167-188.
13. Hildebrandt F, Otto E: Molecular genetics of nephronophthisis and medullary cystic kidney disease. J Am Soc Nephrol 2000, 11(9):1753-1761.
14. Hildebrandt F, Benzing T, Katsanis N: Ciliopathies. N Engl J Med 2011, 364(16):1533-1543.
15. Dell KM: The role of cilia in the pathogenesis of cystic kidney disease. Curr Opin Pediatr 2015, 27(2):212-218.
16. Hildebrandt F, Attanasio M, Otto E: Nephronophthisis: disease mechanisms of a ciliopathy. J Am Soc Nephrol 2009, 20(1):23-35.
2. Gale DP, Oygar DD, Lin F, Oygar PD, Khan N, Connor TM, Lapsley M, Maxwell PH, Neild GH: A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen. Nephrol Dial Transplant 2016, 31(11):1908-1914.
3. Plaisier E, Ronco P: COL4A1-Related Disorders. In: GeneReviews((R)). edn. Edited by Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A. Seattle (WA); 1993.
4. Srivastava S WA, Naidu S.: Alexander Disease. In: GeneReviews® [Internet]. edn. Edited by Adam MP FJ, Mirzaa GM, et al., editors. Seattle (WA): University of Washington, Seattle; 2024: 1993-2024.
5. Shan LD, Peng J, Xiao H, Wu LW, Duan HL, Pang N, Miriam K, Yin F: [Clinical features and COL4A1 genotype of a toddler with hereditary angiopathy with nephropathy, aneurysms and muscle cramps syndrome]. Zhongguo Dang Dai Er Ke Za Zhi 2019, 21(8):754-760.
6. Haga S, Takeguchi R, Tanaka R, Satake A, Makita Y, Yanagi K, Kaname T, Takahashi S: Clinical characteristics of muscle cramps in hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome associated with a novel COL4A1 pathogenic variant: A family case study. Brain Dev 2023, 45(7):390-394.
7. Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, Aguglia U, van der Knaap MS, Heutink P, John SW: Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005, 308(5725):1167-1171.
8. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E et al: COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med 2007, 357(26):2687-2695.
9. Kashtan CE: Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore) 1999, 78(5):338-360.
10. Pozzi A, Zent R: Integrins in kidney disease. J Am Soc Nephrol 2013, 24(7):1034-1039.
11. Tryggvason K, Zhou J, Hostikka SL, Shows TB: Molecular genetics of Alport syndrome. Kidney Int 1993, 43(1):38-44.
12. Van Agtmael T, Bruckner-Tuderman L: Basement membranes and human disease. Cell Tissue Res 2010, 339(1):167-188.
13. Hildebrandt F, Otto E: Molecular genetics of nephronophthisis and medullary cystic kidney disease. J Am Soc Nephrol 2000, 11(9):1753-1761.
14. Hildebrandt F, Benzing T, Katsanis N: Ciliopathies. N Engl J Med 2011, 364(16):1533-1543.
15. Dell KM: The role of cilia in the pathogenesis of cystic kidney disease. Curr Opin Pediatr 2015, 27(2):212-218.
16. Hildebrandt F, Attanasio M, Otto E: Nephronophthisis: disease mechanisms of a ciliopathy. J Am Soc Nephrol 2009, 20(1):23-35.
Published
2025-06-23
How to Cite
Aldarawsha, H., Islam, M. S., & Vasylyeva, T. L. (2025). Persistent microscopic haematuria in a female associated with COL4A1 gene mutation: A case report. International Journal of Integrative Pediatrics and Environmental Medicine, 10, 10 - 14. https://doi.org/10.36013/ijipem.v10i.122
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