Kidney failure in Iranian Families with Hereditary Spherocytosis

Document Type : Original Research

Authors
Z. shahab movahed 1
A. Majd 1
E. Siasi Torbat 2
S. zeinali 3
1 Department of Cellular and Molecular Biology, Faculty of Science, North Tehran Branch of Islamic Azad University, Tehran, Iran
2 Department of Genetics, Faculty of Science, North Tehran Branch of Islamic Azad University, Tehran, Iran
3 Department of Medical Molecular, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, IranKosar Human Genetic Research Center, Tehran, Iran
Abstract
Aims: Anion Exchange Protein 1 (AE1), also known as band 3, is one of the most abundant proteins in the red blood cell membrane and renal tubular a-intercalated cells with two different isoforms (eAE1 and kAE1, respectively). Mutations of the anion exchanger 1 (AE1) gene can cause hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA).

Materials & Methods: In the present Iranian families, five hereditary spherocytosis Patients with symptoms relative to kidney problems which investigated in from the Ali-Asghar Children’s Hospital. A patient suspected dRTA was employed for genetic analyses with whole-exome sequencing and Sanger sequencing methods. Data were analyzed using the Wilcoxon signed-rank test in SPSS Statistic

Findings: Clinical manifestations and laboratory findings of 5 study patients were observed in growth retardation, Splenomegaly, and significant urine infection. Also, one of 5 patients showed severe failure to thrive, Short stature, repeated urinary infection, and weakness. We have found a Combination of a novel homozygote missense variant (c.2494C>T (p.Arg832Cys) in the anion exchanger 1 and a heterozygote missense variant in SPTA1 gene (c. 466C>T (p. Arg156Trp).

Conclusions: These results confirm the importance of Kidney failure with Hereditary Spherocytosis diseases. The combination of two mutations in the Patient 3 manifested as incomplete distal renal tubular acidosis (dRTA) in the affected patient. We reported for the first time, clinical and genetic characteristics of incomplete distal renal tubular acidosis disease in the affected patient.

Keywords

1. Wang, R., et al., Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Science China Life Sciences, 2018. 61(8): p. 947-953.
2. Sinha, R., et al., Distal renal tubular acidosis with hereditary spherocytosis. Indian pediatrics, 2013. 50(7): p. 693-695.
3. Delaunay, J., Red cell membrane and erythropoiesis genetic defects. The hematology journal: the official journal of the European Haematology Association, 2003. 4(4): p. 225-232.
4. Gómez, J., et al., Primary distal renal tubular acidosis: novel findings in patients studied by next-generation sequencing. Pediatric research, 2016. 79(3): p. 496-501.
5.Nurko, S., Anemia in chronic kidney disease: causes, diagnosis, treatment. Cleveland Clinic journal of medicine, 2006. 73(3): p. 289.
6..Atkinson, M.A. and B.A. Warady, Anemia in chronic kidney disease. Pediatric Nephrology, 2018. 33(2): p. 227-238.
7. Kalantar-Zadeh, K. and G.R. Aronoff, Hemoglobin variability in anemia of chronic kidney disease. Journal of the American Society of Nephrology, 2009. 20(3): p. 479-487.
8. Santos, F., et al., Clinical and laboratory approaches in the diagnosis of renal tubular acidosis. Pediatric Nephrology, 2015. 30(12): p. 2099-2107.
9. Park, E., et al., Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous SLC4A1 Mutation in Two Lao Families. Journal of Korean Medical Science, 2018. 33(13).
10. Chu, C., et al., Band 3 Edmonton I, a novel mutant of the anion exchanger 1 causing spherocytosis and distal renal tubular acidosis. Biochemical Journal, 2010. 426(3): p. 379-388.
11. Fawaz, N.A., et al., dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state. European Journal of Haematology, 2012. 88(4): p. 350-355.
12. Pereira, P.C.B., et al., Whole‐exome sequencing as a diagnostic tool for distal renal tubular acidosis. Jornal de Pediatria (Versao em Portugues), 2015. 91(6): p. 583-589.
13. Meng, L.-L., et al., Next-generation sequencing identified a novel SPTB frameshift insertion causing hereditary spherocytosis in China. Annals of hematology, 2019. 98(1): p. 223-226.
14. Eschbach, J.W., The anemia of chronic renal failure: pathophysiology and the effects of recombinant erythropoietin. Kidney international, 1989. 35(1): p. 134-148.
15. Mix, T.C.H., et al., Anemia: a continuing problem following kidney transplantation. American Journal of Transplantation, 2003. 3(11): p. 1426-1433.
16. Radtke, H.W., et al., Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function. 1979.
17. Sharifian, M., et al., Distal Renal Tubular Acidosis and Its Relationship With Hearing Loss in Children Preliminary Report. 2010.
18. Hooman, N., et al., A novel mutation pattern of kidney anion exchanger 1 gene in patients with distal renal tubular acidosis in Iran. Iranian journal of kidney diseases, 2015. 9(3).
19. Watanabe, T., Improving outcomes for patients with distal renal tubular acidosis: Recent advances and challenges ahead. Pediatric health, medicine and therapeutics, 2018. 9: p. 181.
20. Shen, H., et al., Two different pathogenic gene mutations coexisted in the same hereditary spherocytosis family manifested with heterogeneous phenotypes. BMC medical genetics, 2019. 20(1): p. 1-7.
21. Bianchi, P., et al., Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics. haematologica, 2012. 97(4): p. 516-523.
22. Reithmeier, R.A., et al., Band 3, the human red cell chloride/bicarbonate anion exchanger (AE1, SLC4A1), in a structural context. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2016. 1858(7): p. 1507-1532.
23. Khositseth, S., et al., Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients. QJM: An International Journal of Medicine, 2012. 105(9): p. 861-877.
24. BRUCE, L.J., et al., Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells. Biochemical Journal, 2000. 350(1): p. 41-51.
25. Chang, Y.-H., et al., Compound mutations in human anion exchanger 1 are associated with complete distal renal tubular acidosis and hereditary spherocytosis. Kidney international, 2009. 76(7): p. 774-783.
26. Tolpinrud, W., et al., Nonsense mutations of the α-spectrin gene in hereditary pyropoikilocytosis. haematologica, 2008. 93(11): p. 1752-1754.
27. Shmukler, B.E., et al., Hemolytic anemia and distal renal tubular acidosis in two Indian patients homozygous for SLC4A1/AE1 mutation A858D. American journal of hematology, 2010. 85(10): p. 824.
28. Toye, A.M., et al., Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A. Blood, The Journal of the American Society of Hematology, 2008. 111(11): p. 5380-5389.
29. King, M.J. and A. Zanella, Hereditary red cell membrane disorders and laboratory diagnostic testing. International journal of laboratory hematology, 2013. 35(3): p. 237-243.
Pathobiology Reserach
Volume 23, Issue 5
April 2021
Pages 56-74