Balkan Journal of Medical Genetics

FAMILIAL ATYPICAL HEMOLYTIC UREMIC SYNDROME WITH POSITIVE p.S1191L (c.3572C>T) MUTATION ON THE CFH GENE: A SINGLE-CENTER EXPERIENCE
Ersoy Dursun F1,*, Yesil G2, Sasak G3, Dursin H4
*Corresponding Author: Dr. Fadime Ersoy Dursun, Hematoloji Bilim Dalı, Istanbul Medeniyet Universitesi Tıp Fakultesi, Dr. Erkin Cad. No. 6, 34722 Kadıköy, Istanbul, Turkiye. Tel.: +90-536-838-5101. Fax: +90-216-606-5210. E-mail: drfadimeersoy@yahoo.com.tr
page: 81

RESULTS

The laboratory findings of 13 patients included in the study are presented in Table 1. The test results of our index case at the time of admission were as follows: Hb 7.8 g/ dL, PCV 0.23 L/L, platelets 56000.0 mm3, widespread schistocytes in peripheral blood smear, BUN 126.0 mg/dL, Cr 7.8 mg/dL, ADAMTS-13 activity 99.2%, LDH 2350.0 IU/L and haptoglobin <10.0 mg/dL. Based on these results, the patient was diagnosed with aHUS. Of the 13 patients who were screened, three were diagnosed with CRF, one being our index patient and the other two his siblings. The patient also reported six sibling deaths; three of them died of CRF. Besides, genetic screening results showed that the CFH: p.S1191L mutation from the same family was heterozygous. The same mutation was also detected by Sanger sequencing in his mother (DT), three brothers (NT, CT, MT) and nephew (MUT) of the index case (AT), while the sister (SA) and one brother (MNT) did not have any mutations (Figure 1 and Table 1). The family members showing gene mutations included the mother of the index case, three of his brothers, and one of his nephews. The laboratory results of these six cases and seven other family members are shown in Table 1. While all clinical and laboratory findings of the mother (DT), one sibling (NT) and this sibling’s son (MUT), were normal, our index (AT) patient with the heterozygous gene mutation had AKI, and his two siblings (CT and MT) had CRF. These two siblings developed recurrent CRF after they received a renal transplant. Sibling 1 (MT) developed AKI due to an unknown etiology at the age of 7. He applied to another hospital. His initial symptom was shortness of breath, and he was found to have severe hypertension, AKI with a serum Cr of 8.4 mg/dL, anemia with Hb of 7.8 g/dL, and proteinuria. He underwent a kidney biopsy that revealed non specific findings. As there is a crescent in some areas in renal biopsy, it was thought that there might be rapidly progressive glo-merulonephritis. He received six high-dose pulse steroids and continued with oral steroids and 10 sessions of plas-mapheresis. Despite therapy, the disease progress to CRF, and the patient became hemodialysis-dependent. At that time, aHUS was not considered in this patient. The patient received hemodialysis treatment for 6 months, and then renal transplantation was performed from the father. Renal rejection developed 4 months after transplantation. Hemodialysis treatment was started again. The patient was diagnosed with familial aHUS after the diagnosis of our index case. The patient was taken back to the eculizumab (ECZ) treatment and transplantation program. Sibling 2 (CT), a 18-year-old male, developed AKI due to an unknown etiology. He was admitted to another hospital with signs of AKI, like his brother. His initial symptom was shortness of breath, and he was found to have severe hypertension, AKI with a serum Cr of 9.1 mg/dL, anemia with Hb of 8.8 g/dL, and proteinuria. Like his brother, he received steroid and plasmapheresis therapy. Despite therapy, the disease progress to the CRF, and the patient became hemodialysis-dependent. After the patient received hemodialysis treatment for 11 months, he underwent a renal transplant (from a 35-year-old male patient who died of a cerebral hemorrhage). Renal rejection developed 3 months after transplantation. Hemodialysis treatment was started again. The patient was diagnosed with familial aHUS after the diagnosis of our index case. The patient was taken back to the transplantation program and eculizumab treatment. Our index (AT) patient was treated with a total 20 sessions of plasmapheresis (initially, five sessions of plasmapheresis were performed, and then 15 more sessions were performed until the start of ECZ treatment) for 6 weeks and daily fresh frozen plasma therapy. However, upon insufficient response to this treatment, ECZ therapy was initiated. The patient showed a dramatic improvement after treatment with ECZ. The patient’s serum Cr level was reduced to 0.8 mg/dL. Moreover, when the patient became unable to receive ECZ treatment for a while, he once again developed AKI, with his blood Cr level increasing to 6.8 mg/dL. However, the patient’s Hb level decreased to 6.4 g/dL and platelet count to 78000 mm3. Furthermore, the patient developed dilated cardiomyopathy as in some cases reported in the literature [20]. Once the patient received regular ECZ therapy, his AKI symptoms and cardiomyopathy began to improve. The test results on the patient’s last admission were as follows: Hb 13.6 g/dL, PCV 0.40 L/L, platelet 345000.0 mm3, BUN 48 mg/dL, Cr 1.8 mg/ dL, LDH 210.0 IU/L, and haptoglobin 18.2 mg/dL. Longterm follow-up over 1 year showed stable renal function with no relapse. The patient is still being followed by the Departments of Hematology and Nephrology, Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey.

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