Idiopathic Atypical Haemolytic Uraemic Syndrome presenting with acute dystonia.
M Rizwan, KE Maduemem
Department of Paediatrics, Cork University Hospital, Ireland.
Hemolytic Uremic Syndrome (HUS), a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The atypical HUS (aHUS) results from over activation of complement system with formation of micro thrombi and damage to endothelial cells resulting in renal impairment in 50 % and death in 25 %, commonly in untreated patients. We report an intriguing case of aHUS presenting with acute onset of movement disorder and fluctuating delirium.
Hemolytic uremic syndrome a devastating and lethal disease, is the most common cause of acute renal failure in children. aHUS is a Thrombotic Microangiopathy (TMA), which leads to fibrin and platelet-rich thrombi obstructing vessels and causing tissue ischemia. TMA is a microangiopathic hemolytic anemia that presents as a mechanical, nonimmune hemolytic anemia; fragmented erythrocytes (schistocytes); and thrombocytopenia. Elevated plasma lactate dehydrogenase (LDH) is a marker of intravascular hemolysis. In severe cases, liver functions can be deranged.
A previously well ten year old girl presented to the emergency department with a five day history of vomiting which progressively worsened 48 hours before presentation. No history of diarrhea, fever, or sick contacts. She received ondansetron in the community without relief. Her parents reported the onset of unusual posturing episodes overnight after which she appeared confused. She had been anuric for the last 18 hours. On examination she was drowsy, with heart rate of 100/min and respiratory rate of 20/min. Of note she was dehydrated but normotensive. She had an alternating convergent strabismus which her parents noted had been present for a few hours. There was no bruises or petechiae. Cardiorespiratory and gastrointestinal examinations were unremarkable. She demonstrated bilateral intention tremor and past pointing with unsteady gait. She had 3 witnessed “dystonic” events in the department. These involved all limbs and jaw. She had bilateral convergent strabismus with each event. Each episode lasted about one minute and was self-resolving. She subsequently became encephalopathic with fixed bilateral plantar flexors. A non-contrast CT Brain was normal. Full blood count showed Hb 9.5g/dl, WCC 12900/cu mm, and platelets 28000/cu mm; blood film showed schistocytes and microspherocytes. Her renal function was severely impaired with creatinine 1083 umol/L and urea of 80.2 mmol/l. Electrolytes and CK were normal while LDH 5329 U/L and ALT 147 U/L.
She was resuscitated with intravenous fluids before transfer to a regional PICU and remained on peritoneal dialysis for 12 days. She received three red cells and two platelets transfusion. She received three doses of eculizumab before results of negative genetics (Factors H, B, I), ADAMTS 13, autoimmune screen and normal complements were received. She was discharged home after three weeks of admission with improved blood results (Urea 9.5mmol/l, creatinine 95 umol/L, and platelets of 293000).
HUS is characterized by the presence of vascular abnormalities including glomerular endothelial injury and thrombosis1. It can be divided into 2 broad categories: typical (or otherwise D+HUS) and aHUS. D+HUS is more common in children and usually proceeded by a history of diarrhea1. aHUS can be divided into idiopathic and secondary forms. The pathogenesis of idiopathic aHUS involves activation of the complement system2. Genetic aberration in one of the proteins of the alternative complement pathway can be found in at least 50% of idiopathic aHUS patients3,8,9. Genetic aberrations, however, are not the sole cause of complement activation in aHUS. An environmental factor, such as a complement trigger, is probably needed to develop the disease1. In more than half of the cases, the disease is precipitated by an infection, medication, or pregnancy1. Most cases with identifiable mutations are diagnosed during childhood; however, the disease may not manifest until adulthood2. Some children with aHUS do not present with the full triad of HUS, as they may not be thrombocytopenic (15 %) or anemic (6%) or they may have preserved renal function initially (17%)6. Among less usual manifestations, CNS involvement is the most frequent and one that significantly increases morbidity and mortality7. Neurological signs range from epileptic seizures to reduced consciousness level and focal motor deficits8. Our patient showed significant neurological features following a history that suggested atypical HUS. She received eculizumab which has been shown in some studies to improve renal function in aHUS4,5. She is being followed up from the renal point of view.
M. Rizwan, Department of Paediatrics, Cork University Hospital, Ireland.
Email: [email protected]
Conflict of Interest.
There is no conflict of interest.
1. Loirat C, Frémeaux-Bacchi V: Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011;6:60.
2. Noris M, Remuzzi G: Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-1687.
3. Mache CJ, Acham-Roschitz B, Frémeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedl S, Vester U, Ring E: Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2009;4:1312-1316.
4. Giordano M, Castellano G, Messina G, et al Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report. Pediatrics. 2012;130(5):e1385–e1388pmid:23027168
5. Besbas N, Gulhan B Karpman D, Topaloglu R Duzova A, Korkmaz E, Ozaltin F, Neonatal onset atypical hemolytic uremic syndrome successfully treated with eculizumab. Pediatr Nephrol. 2013;28(1):155–158pmid:22956028.
6. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat, C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562.
7. Oakes RS, Siegler RL, McReynolds MA, Payesher T, Pavia AT:Predictors of fatality in postdiarrheal hemolytic uremic syndrome. Pediatrics. 2006; 117(5): 1656–62. Nathanson S, Kwon T, Elmaleh M, Charbit M, Launay EA, Harambat J, Brun M, Ranchin B, Bandin F, Cloarec S, Bourdat-Michel G, Pietrement C, Champion G, Ulinska T, Deschenes G.
8. Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2010; 5(7): 1218–28. Steinborn M, Leiz S, Rüdisser K, Griebel M, Harder T, Hanhn H.: CT and MRI in haemolytic uraemic syndrome with central nervous system involvement: distribution of lesions and prognostic value of imaging findings. Pediatr Radiol. 2004; 34(10): 805–10.