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An Infant Case of Streptococcus Pneumoniae-Associated Thrombotic Microangiopathy with Heterozygous CFI Mutation and
Yuji Matsumoto1, Yohei Ikezumi1, Tomomi Kondoh1
1Department of Pediatrics, Fujita Health University School of Medicine.
Abstract:
Thrombotic microangiopathy (TMA) is a disease that causes organ damage due to microvascular hemolytic anemia, thrombocytopenia, and microvascular platelet thrombosis. Streptococcus pneumoniae-associated TMA (spTMA) is a rare complication of invasive pneumococcal infection. In addition, atypical hemolytic uremic syndrome (aHUS) is TMA associated with congenital or acquired dysregulation of complement activation. We report the case of a nine-month-old boy with refractory nephrotic syndrome complicated by spTMA in the setting of heterozygous complement factor-I (CFI) gene mutation and CFHR3-CFHR1 deletion. He repeatedly developed thrombocytopenia, anemia with schistocytes, hypocomplementemia, and abnormal coagulation triggered by infection, which manifested clinically with convulsions and an intraperitoneal hematoma. Eculizumab (a monoclonal humanized anti-C5 antibody) provided transient symptomatic benefit including improvement in thrombocytopenia; however, he developed unexplained cardiac arrest and was declared brain dead a few days later. In this report, we highlight the diagnostic challenges of this case and the causal relationship between spTMA and complement abnormalities and consider the contribution of heterozygous mutation of CFI and CFHR3-CFHR1 deletion.
Insights
A rare Streptococcus pneumoniae-associated thrombotic microangiopathy (spTMA) complicated a boy
Area of Science:
- Nephrology
- Hematology
- Immunology
Background:
- Thrombotic microangiopathy (TMA) involves microvascular platelet thrombosis, hemolytic anemia, and thrombocytopenia, leading to organ damage.
- Streptococcus pneumoniae-associated TMA (spTMA) is a rare, severe complication of invasive pneumococcal infections.
- Atypical hemolytic uremic syndrome (aHUS) is a TMA characterized by dysregulation of the complement system.
Observation:
- A nine-month-old boy with nephrotic syndrome developed spTMA.
- The patient presented with recurrent thrombocytopenia, anemia with schistocytes, hypocomplementemia, and coagulopathy.
- Clinical manifestations included convulsions and an intraperitoneal hematoma, triggered by infection.
Findings:
- The patient had a heterozygous complement factor-I (CFI) gene mutation and a CFHR3-CFHR1 deletion.
- Eculizumab treatment yielded transient improvement in thrombocytopenia but did not prevent cardiac arrest.
- This case highlights the diagnostic complexity of spTMA in conjunction with genetic complement abnormalities.
Implications:
- The study underscores the critical role of complement system dysregulation in spTMA.
- Genetic factors, including CFI mutations and CFHR deletions, may predispose individuals to TMA.
- Understanding these interactions is crucial for managing complex TMA cases, particularly in pediatric patients.
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