Atypical haemolytic uraemic syndrome: a case of rare genetic mutation

Complement-mediated kidney disease has been an evolving area in the field of nephrology. Atypical haemolytic uraemic syndrome (aHUS) is a rare thrombotic microangiopathy that affects multiple organs, particularly kidneys. The disease is characterised by a triad of haemolytic anaemia, thrombocytopenia and acute kidney injury (AKI). aHUS is most commonly caused by dysregulation of alternative complement pathway. In contrast to shiga toxin-associated haemolytic uraemic syndrome, diarrheal prodrome is usually absent in children with aHUS. We report a 2-year, 9-month-old boy who presented with acute dysentery and AKI. He had an unusual prolonged course of illness with hypocomplementaemia; hence, genetic testing was performed. He had a storming course in the hospital and succumbed to complications of the disease. Genetic study revealed digenic mutation in Complement Factor I and C3. Therefore, it is important to differentiate aHUS from other thrombotic microangiopathies to improve the outcome.

Successful treatment with eculizumab in a patient with pregnancy-associated atypical hemolytic uremic syndrome

Pregnancy‐associated atypical haemolytic uraemic syndrome is a rare and potentially lethal complement-mediated disorder. It can mimic preeclampsia, gestational hypertension, thrombotic thrombocytopenic purpura and hemolysis, elevated liver enzymes and low platelets syndrome. Thus, it can be hard to distinguish pregnancy‐associated atypical haemolytic uraemic syndrome from other causes in peri/post-partum women presenting with features of microangiopathic haemolytic anemia, thrombocytopenia and acute kidney injury. We present a case of a 35-year-old woman in her third pregnancy at 32 weeks’ gestation who underwent caesarean section due to fetal distress. She developed severe renal impairment, thrombocytopenia and neurologic symptoms within 24 hours after delivery. A diagnosis of pregnancy‐associated atypical haemolytic uraemic syndrome was provided, and treatment with plasma therapy followed by eculizumab was initiated. A rapid improvement of both clinical and laboratory parameters was observed. This case demonstrates the significance of early initiation of anti-complement therapy to prevent irreversible renal damage and possible death in women with pregnancy‐associated atypical haemolytic uraemic syndrome.

MO107CLINICAL CHARACTERISTICS OF A PATIENT POPULATION WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME AND MALIGNANT HYPERTENSION: THE GLOBAL AHUS REGISTRY ANALYSIS

Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a rare disease that manifests as complement-mediated thrombotic microangiopathy (TMA), which can lead to severe organ damage. Some patients with aHUS may present with malignant hypertension (MHT); both conditions can result in TMA. The objective of this analysis was to characterise patients with aHUS and MHT. Method In this analysis, patients from the Global aHUS Registry (NCT01522183) were included if they were diagnosed with MHT and were followed ≥90 days after initial aHUS symptom presentation or diagnosis date; patients were excluded if they withdrew from the registry or discontinued treatment with eculizumab due to a diagnosis other than aHUS. Demographics and clinical characteristics were evaluated. Results Seventy-one of 1903 registry patients were included in the analysis. Clinical characteristics are presented in the table. Seventeen patients (24%) had a paediatric (<18 years) onset of disease, and 54 (76%) were adults at aHUS diagnosis; female patients were slightly overrepresented (61%). Sixty-nine percent of patients were reported to have MHT at around the same time as aHUS diagnosis (+/-2 months), while 11% and 13% experienced MHT before and after aHUS diagnosis, respectively. aHUS triggering conditions were reported in 6/71 patients (8%) (Table). Cardiovascular (27%) and gastrointestinal (21%) symptoms were the most commonly reported extra-renal manifestations. Eight patients (11%) had a reported family history of aHUS and 40 patients (56%) had a complement pathogenic variant or an anti-CFH-antibody. Thirty-three patients (46%) had a kidney transplant; of these, 20 were prescribed eculizumab in the peri- or post-transplant period. Conclusion In this analysis of patients with aHUS and MHT, the observed high prevalence of pathogenic variants in complement genes or anti-CFH antibodies, alongside the high proportion of patients with extrarenal manifestations and/or requiring kidney transplant, indicate a high severity of presentation and poor prognosis of aHUS associated with MHT.

A patient with a homozygous diacylglycerol kinase epsilon (DGKE) gene mutation with atypical haemolytic uraemic syndrome and low C3 responded well to eculizumab: a case report

Background Atypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury. In most cases, alternative complement pathway dysregulation is the identifying cause. Recently, other genetic causes have been identified, including a mutation in the diacylglycerol kinase epsilon (DGKE) gene, which theoretically affect the coagulation pathway and does not affect the complement pathway. Data about the management of these patients are limited. Ideal management and definitive treatment protocols have not yet been established. Case presentation A three-year-old boy presented with features of atypical haemolytic uraemic syndrome (aHUS) and low complement C3. He was presumed to have complement-mediated aHUS and was managed empirically with eculizumab. Two weeks after starting eculizumab, his haemoglobin levels, platelet count, and complement C3 level normalized but he continued to have non-nephrotic range proteinuria. His genetic testing revealed a homozygous DGKE mutation, with no other mutation detected. Six months after presentation, the patient was still in remission with no features of aHUS, a trial of weaning eculizumab by increasing dose interval was followed by nephrotic range proteinuria and severe oedema. His proteinuria improved and his oedema resolved after resuming his recommended eculizumab dose. Conclusions DGKE gene mutation can lead to aHUS with theoretically no complement dysregulation. However, some patients with this mutation show alternative complement pathway activation. This case report describes a patient with aHUS due to a DGKE gene mutation and low C3 levels who responded to eculizumab, adding to the previously reported cases of patients with DGKE gene mutations who had complete remission with no relapse with C5 blockers and/or plasma exchange. A randomized controlled study on patients with DGKE mutations might be beneficial in understanding the disease and generating a management protocol.

Correction to: Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome

The article Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome, written by Yahiya Y. Syed, was originally published electronically in SpringerLink on 18 March 2021 without open access.