A 51-year-old Chinese woman presented with status epilepticus in May 2024. Four months previously, she had been admitted for abdominal pain. Computed tomography (CT) of the abdomen and pelvis at the time was unremarkable. She had remained well until she developed upper respiratory tract infection symptoms, followed by recurrent abdominal pain and vomiting for 2 days. Her mental status deteriorated with irritability and mutism, followed by recurrent generalised tonic-clonic seizures. Physical examination was unremarkable. She was intubated and managed in the intensive care unit with multiple anticonvulsants.

The initial plain CT of the brain was normal, but follow-up CT revealed new bilateral cerebellar, thalamic and occipital hypodensities (Fig 1). Blood tests showed thrombocytopenia (platelet count: 36×109/L, reference: 145-370) and acute kidney injury (creatinine level: 663 μmol/L, reference: 49-83). Haemoglobin level dropped to 6.6 g/dL (reference: 11.7-14.9) over the subsequent days with identifiable schistocytes, raised lactate dehydrogenase level (2532 U/L, reference: 103-199), raised indirect bilirubin level (direct-to-total bilirubin: 14:39 μmol/L), undetectable haptoglobin level (<0.07 g/L, reference: 0.30-2.00), reticulocytosis (133.2×10⁹/L, reference: 20-101; 5.9%) and negative direct antiglobulin test, suggestive of microangiopathic haemolytic anaemia. Kidney biopsy confirmed thrombotic microangiopathy (TMA) with congested glomeruli, double contours, and capillary thrombi on fibrin staining (Fig 2).

ADAMTS13 activity was normal at 75.4% (reference: 60.6%-130.6%; <10% signifies severe deficiency1). Stool culture and polymerase chain reaction for Shiga toxin genes, urine Streptococcus pneumoniae soluble polysaccharide antigen, polymerase chain reaction of nasopharyngeal swab for common respiratory viruses, as well as serological tests for human immunodeficiency virus, cytomegalovirus and Epstein-Barr virus were all negative. Antinuclear antibodies, anti–double-stranded DNA antibodies, antiphospholipid antibodies, antibodies to extractable nuclear antigen, anti–topoisomerase I antibody and antineutrophil cytoplasmic antibodies were likewise negative. Complement component 3 and complement component 4 were normal. Results of homocysteine and amino acid chromatography excluded cobalamin C deficiency. Urine tests were negative for pregnancy and drugs that might induce TMA. There were no clinical features suggestive of malignancy. The diagnosis of atypical haemolytic uraemic syndrome (aHUS) with multisystem (gastrointestinal, neurological and kidney) involvement, possibly triggered by upper respiratory tract infection, was made. The patient was apnoeic and anuric, necessitating ventilatory and haemodialysis support.

Experience sharing from paediatric nephrology colleagues facilitated prompt testing for anti–factor H antibody (anti-FH), complement functional assays (CH50, AH50, and sC5b9) and genetic analysis for variants related to aHUS. Urgent application was made through the expert panel of the Hospital Authority for eculizumab, a complement component 5 (C5) inhibitor. Anti–factor H antibody level was raised to 11.6 U/mL (reference: <10) but no pathogenic variants were detected by next-generation sequencing or multiplex ligation-dependent probe amplification analysis of the aHUS genetic panel including the following genes: CFH, CFB, CFI, MCP, C3, CFHR1, CFHR3, CFHR5, DGKE and MMACHC (see online Appendix for the full names of genes).

In view of the likely diagnosis of complement-mediated HUS, the first dose of eculizumab was given 7 days after admission. Improvement in haematological indices and renal recovery were evident within the first and third week, respectively. She was extubated 12 days after eculizumab commencement and had been weaned off haemodialysis after 4 weeks. Repeat CT of the brain confirmed resolution of previous abnormalities (Fig 1). She was seizure-free and ambulatory with full neurological recovery upon discharge at 10 weeks post-hospitalisation. Prednisolone and mycophenolate mofetil were started while eculizumab was weaned off after 28 weeks of treatment. Her platelet count, lactate dehydrogenase level, haptoglobin level and kidney function have remained normal on serial monitoring.

Atypical haemolytic uraemic syndrome is a form of TMA caused by dysregulation of the complement pathway.1 The nomenclature of the disease is evolving.2 In 50% to 60% of patients, either complement gene variants or anti-FH autoantibodies result in dysregulation of the alternative pathway.1 Clinical features include microangiopathic haemolytic anaemia, thrombocytopenia and end-organ injury, most commonly acute kidney injury.3 Extrarenal manifestations involving neurological, gastrointestinal, pulmonary and cardiovascular systems are also seen.4 Half of the affected cases are preceded by triggers such as infections, medications and pregnancy.1 The annual incidence of aHUS has been reported as 0.5 to 2 per million, of whom 41% to 58% of cases are adults.1 This is contrary to the traditional belief that it is a childhood condition.1 Under recognition of aHUS might be attributed to inexperience of the disease and its diagnostic algorithm.

The diagnosis of aHUS requires urgent evaluation to exclude other types of TMA, namely thrombotic thrombocytopenia, Shiga toxin–producing Escherichia coli–haemolytic uraemic syndrome and different secondary forms.3 It is often a challenge to differentiate a complement-mediated TMA with a trigger from a secondary TMA. A full battery of tests is required to thoroughly exclude alternative diagnoses once TMA is recognised,5 as in our case. Complement studies, anti-FH antibody titre and genetic analysis are essential in the diagnostic pathway.5 A normal complement component 3 level in our patient was not surprising since it is reported low in only about 50% of cases.3 Genetic screening is particularly important as it correlates with the response to treatment, risk of relapse, and prognosis.3 Nevertheless a negative genetic test does not exclude the diagnosis of complement-mediated TMA since about 40% of patients have no variants identified.5

The outcome of aHUS has been historically poor prior to the development of complement inhibitors. Eculizumab and ravulizumab are anti-C5 monoclonal antibodies that block the terminal complement pathway.5 Eculizumab has been shown to prolong the 5-year end-stage kidney disease-free survival of aHUS patients from 39.5% to 85.5%.5 In Hong Kong, eculizumab or ravulizumab may be publicly funded for indicated patients, but only with prior approval from a local expert panel.6 Physicians should take note of the available resources, including the diagnostic and management pathways, and the funding procedure in relation to aHUS to facilitate appropriate patient care.

This case illustrates the effect response of an adult patient with complement-mediated aHUS to C5 inhibitors, highlighting the importance of timely recognition, evaluation and management of this rare condition.

Concept or design: YK Yam, SK Yuen.
Acquisition of data: YK Yam.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: YK Yam.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors acknowledge the invaluable contribution of the Intensive Care Unit and the Department of Pathology at the Caritas Medical Centre in the care of this patient.

Preliminary results of the case have been presented as poster presentation at the 5th International Congress of Chinese Nephrologists cum Hong Kong Society of Nephrology Annual Scientific Meeting 2024, Hong Kong, 13-15 December 2024.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. Informed consent for all treatment and procedures was obtained from the patient or her next-of-kin. Verbal consent for publication was obtained from the patient.

The supplementary material was provided by the authors and some information may not have been peer reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by the Hong Kong Academy of Medicine and the Hong Kong Medical Association. The Hong Kong Academy of Medicine and the Hong Kong Medical Association disclaim all liability and responsibility arising from any reliance placed on the content.

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2. Nester CM, Feldman DL, Burwick R, et al. An expert discussion on the atypical hemolytic uremic syndrome nomenclature—identifying a road map to precision: a report of a National Kidney Foundation Working Group. Kidney Int 2024;106:326-36. Crossref

3. Goodship TH, Cook HT, Fakhouri F, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 2017;91:539-51. Crossref

4. Schaefer F, Ardissino G, Ariceta G, et al. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int 2018;94:408-18. Crossref

5. Kavanagh D, Ardissino G, Brocklebank V, et al. Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int 2024;106:1038-50. Crossref

6. Hong Kong SAR Government. LCQ16: Support for patients with rare diseases [press release]. 12 Jun 2024. Available from: https://www.info.gov.hk/gia/general/202406/12/P2024061200662.htm. Accessed 18 Nov 2025.