Macrovascular Involvement in a Child with Atypical Hemolytic Uremic Syndrome

Background: Atypical hemolytic uremic syndrome (aHUS) is a disorder of the complement system which leads to thrombotic microangiopathy. It is caused by either acquired or hereditary defects in the activation or regulation of the alternative complement pathway and is therefore considered to be a disease of local complement dysregulation in microvasculature with predominantly renal involvement. However, extrarenal manifestations are observed in approximately one-fifth of aHUS patients, with the myocardium and central nervous system (CNS) being involved most often. Additionally, there have been a few reports of aHUS with cerebral artery stenoses or periphereal gangrene, suggesting the possibility of 'macrovascular' involvement in aHUS.

Case-diagnosis/treatment: We present a child with early onset aHUS and a C3 gain-of-function mutation who developed cerebral artery stenoses, leading ultimately to death due to a massive stroke 9 days after successful renal transplantation under prophylactic eculizumab treatment. Similar cases described in the literature are also briefly summarized.

Conclusions: The disease course in our patient with aHUS confirms that dysregulated complement activation can induce arterial steno-occlusive lesions in the absence of acute episodes of HUS. Further studies are required to document the frequency of such macrovascular complications and the role of eculizumab treatment in preventing their development and progression.