PP13.3 – 2868: Dramatic neurological outcome at one year in a 4 week old with atypical haemolytic syndrome (aHUS)

Abstract

A 4 week old baby presented with bloody diarrhoea and subsequent right and left focal tonic and clonic seizures. She then developed haemolytic anaemia, thrombocytopenia and acute renal failure, requiring admission to PICU. Her neurological status deteriorated with decreased consciousness, extensor/dystonic posturing, pyramidal signs bilaterally and increasing head circumference. She was diagnosed clinically with aHUS. aHUS is a rare life threatening genetic disorder caused by chronic uncontrolled complement activation. It is characterised by a systemic thrombotic microangiopathy which targets both the kidneys and brain. She was treated with Eculizumab (a monoclonal antibody) given on days 1and 8 of PICU and continues treatment on a three weekly basis. She is the first neonate treated effectively with ecluzimab to be reported in the literature. Investigations: Initial CT scan and infective screen including lumbar puncture was normal. EEG showed a discontinuous background with periods of suppression in either hemisphere. Initial MRI showed restricted diffusion in the white matter and corpus callosum, upper thalami and lentiform nucleus. Investigations out ruled congenital TTP or an infective/metabolic cause. There has been no known pathogenic mutation identified (CFH, CFI CD46, C3, CFB, DGKE, THBD, CFHR1 and CFH13 negative). Her complement factor H and factor I levels are normal and there are no antibodies for anti-factor H autoantibodies. Outcome Her neurological signs resolved dramatically after the second dose of Eculizumab (day 10 of illness). Repeat MRI scan 2 months after the initial presentation showed resolution of the areas of diffusion restriction and only mild periventricular change. Neurological examination at 16 months confirmed a normal neurodevelopmental outcome with mild central and peripheral hypotonia. Conclusion Neonatal aHUS presenting with severe neurological involvement and characteristic MRI findings (restricted diffusion in the basal ganglia and white matter) has a good neurological outcome when treated early with Eculizumab. A 4 week old baby presented with bloody diarrhoea and subsequent right and left focal tonic and clonic seizures. She then developed haemolytic anaemia, thrombocytopenia and acute renal failure, requiring admission to PICU. Her neurological status deteriorated with decreased consciousness, extensor/dystonic posturing, pyramidal signs bilaterally and increasing head circumference. She was diagnosed clinically with aHUS. aHUS is a rare life threatening genetic disorder caused by chronic uncontrolled complement activation. It is characterised by a systemic thrombotic microangiopathy which targets both the kidneys and brain. She was treated with Eculizumab (a monoclonal antibody) given on days 1and 8 of PICU and continues treatment on a three weekly basis. She is the first neonate treated effectively with ecluzimab to be reported in the literature. Investigations: Initial CT scan and infective screen including lumbar puncture was normal. EEG showed a discontinuous background with periods of suppression in either hemisphere. Initial MRI showed restricted diffusion in the white matter and corpus callosum, upper thalami and lentiform nucleus. Investigations out ruled congenital TTP or an infective/metabolic cause. There has been no known pathogenic mutation identified (CFH, CFI CD46, C3, CFB, DGKE, THBD, CFHR1 and CFH13 negative). Her complement factor H and factor I levels are normal and there are no antibodies for anti-factor H autoantibodies. Her neurological signs resolved dramatically after the second dose of Eculizumab (day 10 of illness). Repeat MRI scan 2 months after the initial presentation showed resolution of the areas of diffusion restriction and only mild periventricular change. Neurological examination at 16 months confirmed a normal neurodevelopmental outcome with mild central and peripheral hypotonia. Neonatal aHUS presenting with severe neurological involvement and characteristic MRI findings (restricted diffusion in the basal ganglia and white matter) has a good neurological outcome when treated early with Eculizumab.