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<p>Two male siblings, aged 15 and 13&#xa0;years, born to consanguineous parents, presented with hereditary anemia and thrombocytopenia associated with unexplained hepatosplenomegaly. Both were initially diagnosed with hereditary cytopenia and maintained on transfusion therapy since childhood. At age 15, the elder sibling developed acute thrombotic microangiopathy (TMA) with hypertensive encephalopathy, hemolytic anemia, severe thrombocytopenia, and acute kidney injury requiring hemodialysis and plasma exchange. The younger sibling exhibited predominantly hematological manifestations with severe anemia and thrombocytopenia but preserved kidney function, responding favorably to plasma transfusion. Whole-exome sequencing identified two distinct pathogenic variants: a homozygous mutation in <i>ADAMTS13</i> associated with hereditary thrombotic thrombocytopenic purpura (TTP; OMIM 274150), and a homozygous 57.1&#xa0;Kb deletion at 1q31.3 involving <i>CFHR1</i> and <i>CFHR3</i>, associated with atypical hemolytic uremic syndrome (aHUS; OMIM 235400). This case series highlights the phenotypic variability of TMA syndromes and underscores the importance of comprehensive genetic testing in hereditary cytopenia.</p>

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Dual pathogenic variants in ADAMTS13 and CFHR1/CFHR3 deletion: divergent thrombotic microangiopathy phenotypes in siblings

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月11日

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  • Mona Hamed Gehad,
  • Doaa M. Youssef,
  • Amal S. El-Shal,
  • Mona Mohammed Elsharkawy,
  • Amal E. Gohary

摘要

Two male siblings, aged 15 and 13 years, born to consanguineous parents, presented with hereditary anemia and thrombocytopenia associated with unexplained hepatosplenomegaly. Both were initially diagnosed with hereditary cytopenia and maintained on transfusion therapy since childhood. At age 15, the elder sibling developed acute thrombotic microangiopathy (TMA) with hypertensive encephalopathy, hemolytic anemia, severe thrombocytopenia, and acute kidney injury requiring hemodialysis and plasma exchange. The younger sibling exhibited predominantly hematological manifestations with severe anemia and thrombocytopenia but preserved kidney function, responding favorably to plasma transfusion. Whole-exome sequencing identified two distinct pathogenic variants: a homozygous mutation in ADAMTS13 associated with hereditary thrombotic thrombocytopenic purpura (TTP; OMIM 274150), and a homozygous 57.1 Kb deletion at 1q31.3 involving CFHR1 and CFHR3, associated with atypical hemolytic uremic syndrome (aHUS; OMIM 235400). This case series highlights the phenotypic variability of TMA syndromes and underscores the importance of comprehensive genetic testing in hereditary cytopenia.