Keyword: Genetic Diagnosis
1 result found.
Congress Abstract
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A23, https://doi.org/10.63946/cajn/19533
ABSTRACT:
Introduction and Aim: Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease that requires differential diagnosis from other thrombotic microangiopathies (TMAs). The aim of this study was to determine the diagnostic value of ADAMTS13 activity levels, anti‑complement factor H (anti‑CFH) antibody titers, and genetic screening in verifying aHUS subtypes among the pediatric population in Kazakhstan.
Materials and Methods: A retrospective analysis was conducted on 15 children with aHUS (8 girls and 7 boys) from 8 regions of Kazakhstan between 2019 and 2025. The mean age was 7.2 ± 3.8 years. ADAMTS13 activity was measured in 7 patients (46.6%), and anti‑CFH titers were assessed in 10 patients (66.7%). In the remaining patients, these tests were not performed because they had received fresh frozen plasma transfusions prior to testing. Genetic testing was completed for 10 out of 15 children (66.7%); the remaining 5 patients (33.3%) died before testing could be carried out.
Results: In all patients tested (n = 7, 100%), ADAMTS13 activity was >10%, effectively ruling out thrombotic thrombocytopenic purpura (TTP). Autoimmune aHUS associated with anti‑CFH antibodies was diagnosed in 4 out of 10 children (40%), of whom 3 were of Asian descent and 1 was Caucasian. Genetic testing in 10 children revealed pathogenic variants in complement system genes in 2 patients (20%): one child had a CFHR3/CFHR1 deletion, and another had a CFHR1/CFHR4 microdeletion; both exhibited high anti‑CFH titers (up to 11,490 U/mL). Additionally, one child was found to have a clinically insignificant heterozygous autosomal recessive mutation in the ADAMTS13 gene.
The comprehensive laboratory workup allowed for the stratification of aHUS subtypes and personalized therapy. Patients with idiopathic forms received complement‑blocking therapy with eculizumab alone, while children with anti‑CFH antibodies received combined treatment with eculizumab and immunosuppressive agents.
Conclusions: This is the first comprehensive diagnostic data report on pediatric aHUS in Kazakhstan. Genetically determined aHUS was identified in 20% of the cohort. Anti‑CFH–associated aHUS appears to occur more frequently in the Asian population (reported as 50–60% in Indian cohorts by Khandelwal et al.) compared to Caucasians (5–25%). Our findings represent an intermediate frequency between European and Asian populations, which is consistent with the mixed ethnic composition of the Kazakhstani cohort.
Materials and Methods: A retrospective analysis was conducted on 15 children with aHUS (8 girls and 7 boys) from 8 regions of Kazakhstan between 2019 and 2025. The mean age was 7.2 ± 3.8 years. ADAMTS13 activity was measured in 7 patients (46.6%), and anti‑CFH titers were assessed in 10 patients (66.7%). In the remaining patients, these tests were not performed because they had received fresh frozen plasma transfusions prior to testing. Genetic testing was completed for 10 out of 15 children (66.7%); the remaining 5 patients (33.3%) died before testing could be carried out.
Results: In all patients tested (n = 7, 100%), ADAMTS13 activity was >10%, effectively ruling out thrombotic thrombocytopenic purpura (TTP). Autoimmune aHUS associated with anti‑CFH antibodies was diagnosed in 4 out of 10 children (40%), of whom 3 were of Asian descent and 1 was Caucasian. Genetic testing in 10 children revealed pathogenic variants in complement system genes in 2 patients (20%): one child had a CFHR3/CFHR1 deletion, and another had a CFHR1/CFHR4 microdeletion; both exhibited high anti‑CFH titers (up to 11,490 U/mL). Additionally, one child was found to have a clinically insignificant heterozygous autosomal recessive mutation in the ADAMTS13 gene.
The comprehensive laboratory workup allowed for the stratification of aHUS subtypes and personalized therapy. Patients with idiopathic forms received complement‑blocking therapy with eculizumab alone, while children with anti‑CFH antibodies received combined treatment with eculizumab and immunosuppressive agents.
Conclusions: This is the first comprehensive diagnostic data report on pediatric aHUS in Kazakhstan. Genetically determined aHUS was identified in 20% of the cohort. Anti‑CFH–associated aHUS appears to occur more frequently in the Asian population (reported as 50–60% in Indian cohorts by Khandelwal et al.) compared to Caucasians (5–25%). Our findings represent an intermediate frequency between European and Asian populations, which is consistent with the mixed ethnic composition of the Kazakhstani cohort.
