Incidence of Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical HUS is an extremely rare disease with an annual incidence ranging from 0.23 to 1.9 cases per million population across all ages, and a prevalence of approximately 4.9 per million population. 1
Global Incidence Estimates
The incidence of aHUS varies by age group and geographic region:
- All ages: Annual incidence ranges from 0.23 to 1.9 per million population 1
- Pediatric and young adult population (≤20 years): Annual incidence ranges from 0.26 to 0.75 per million population 1
- United States estimate: Approximately 2 per 1,000 population 2
These estimates come from systematic review data primarily derived from European countries (France, Norway, Italy) and Oceania (Australia), representing the most comprehensive epidemiologic assessment available. 1
Prevalence Data
Prevalence estimates show more variability than incidence data:
- All ages: Approximately 4.9 per million population 1
- Age ≤20 years: Ranges from 2.2 to 9.4 per million population 1
The higher variability in prevalence reflects differences in case definitions, diagnostic criteria, and survival rates across different healthcare systems. 1
Age and Sex Distribution
A distinct sex-specific pattern emerges based on age at disease onset:
- Childhood presentation: Male-to-female ratio of 1.3:1 3
- Adult presentation: Male-to-female ratio of 1:2 (females predominate) 3
This sex-age effect differs markedly from typical (STEC-associated) HUS, which represents 90% of pediatric HUS cases but is not the focus of this incidence discussion. 4
Geographic Limitations
Critical caveat: The available epidemiologic data are heavily skewed toward European populations, with minimal data from Asia, Africa, or South America. 1 The true global incidence may differ substantially in regions where systematic surveillance is lacking. 1
Clinical Implications of Rarity
The extreme rarity of aHUS (approximately 1-2 cases per million annually) means:
- Most general practitioners will never encounter a case in their career 1
- Delayed diagnosis is common, as the disease may not be considered in the differential diagnosis 5
- Mortality at first presentation is approximately 25%, and 50% of patients progress to end-stage renal disease if treatment is delayed 5
- Early recognition is critical, as complement inhibitor therapy (eculizumab/ravulizumab) must be initiated immediately when the diagnostic triad is confirmed 4
Genetic Mutation Frequency
Among diagnosed aHUS patients, 50-60% harbor identifiable genetic mutations in complement regulatory genes, while 40-50% have no detectable mutation despite meeting clinical diagnostic criteria. 6, 7 This incomplete genetic penetrance means that incidence estimates based solely on genetic screening would substantially underestimate true disease burden. 7