Hemolytic uremic syndrome with Mycoplasma pneumoniae infection and membrane cofactor protein mutation – case report

Thrombotic microangiopathies (TMA) are rare life-threatening diseases of various etiologies, making the identification of the specific forms and appropriate treatment difficult. The aim of this work is to present the history of a patient with atypical hemolytic uremic syndrome (aHUS) that developed in the context of Mycoplasma pneumoniae infection. Case presentation: A 5 - year old, Caucasian, previously healthy girl presented with symptoms of HUS, without preceding diarrhoea and with ongoing upper respiratory tract infection. ADAMTS13 deficiency and presence of Shiga-like toxin producing E. coli (STEC) was excluded, and the diagnosis of aHUS verified. She required peritoneal dialysis for 4 days and fresh frozen plasma (FFP) treatment was started with good clinical response. Serological investigation for Mycoplasma pneumoniae was positive (IgM) leading to the initiation of clarithromycin therapy. The complement profile (classical pathway activity, C3 and C4 serum levels were slightly decreased, no signs of alternative pathway dysregulation) was indicative for classical pathway activation and consumption. The genetic screening revealed a novel non-synonymous variation in the CD46 (MCP) gene in heterozygous form that causes a proline to leucine change at codon 155 of the MCP (P155L). The CD46 P155L variation was associated in the samples of the patient and family members with decreased MCP protein expression on the surface of granulocytes. In addition to the P155L mutation, multiple frequent aHUS risk variations were also identified. Conclusion: The diagnosis of aHUS is challenging and is based mainly on the exclusion of ADAMTS13 deficient thrombotic thrombocytopenic purpura (TTP) and typical HUS caused by STEC. Our patient had single-episodic HUS in the context of upper-airway infection, and finally a functionally relevant CD46 (MCP) mutation was identified. The complexity of aHUS, and the importance of the requirement for full differential diagnostic workup of all HUS cases is further highlighted by the current case history.