Declining fertility rates may reshape future hereditary angioedema case numbers

Hereditary angioedema, a rare and potentially life-threatening disorder, could become even rarer in the decades ahead as birth rates continue to fall worldwide, according to a correspondence published in Allergy, Asthma & Clinical Immunology. The letter, authored by Lauren Wong, Harold Kim and Mark Kuprowski, examines how sustained declines in total fertility rates and shrinking populations may influence the future number of new cases of the disease, and argues that the way rare conditions are approached should be re-examined in light of these demographic shifts.

Hereditary angioedema is caused by autosomal dominant mutations in the SERPING1 gene, which lead to a deficiency or dysfunction of C1 esterase inhibitor. Recent estimates place global prevalence of the condition at 1.22 per 100,000 individuals. Because the disorder follows an autosomal dominant inheritance pattern, each child of an affected parent has a substantial chance of inheriting the mutation. The authors point out that several developed countries now fall well below the population replacement rate, placing them in what demographers describe as an “ultra-low fertility” group, and that this trend provides reason to reconsider how the burden of rare diseases such as hereditary angioedema may evolve.

Beyond the raw arithmetic of fewer births, the letter highlights several disease-specific factors that could further shape future case counts. One is reproductive hesitancy: people who carry or are at risk of carrying an autosomal dominant mutation may choose to have fewer children, a decision that would compound the effect of falling fertility rates at the population level. Another is the observation that estrogen is associated with exacerbation of angioedema attacks, a factor the authors suggest may influence reproductive considerations for patients. The letter also raises the possibility that complement dysregulation, the underlying biological mechanism of the disease, could have effects on fertility itself, though these remain questions for further study rather than established findings.

The authors frame these demographic considerations as relevant not only to clinicians and researchers but also to pharmaceutical companies involved in hereditary angioedema care. If the number of new cases declines over time, planning for treatment capacity, drug development and clinical services may need to account for a changing patient population. They argue that better characterizing population changes in the context of reduced fertility rates may help inform long-term clinical planning and the development of novel therapies, both for hereditary angioedema and for other rare diseases that share similar inheritance patterns. As a correspondence piece, the letter presents a forward-looking analysis grounded in current prevalence estimates and demographic trends rather than new clinical data, offering a framework for thinking about how one of the quieter consequences of falling birth rates could reach the clinic.

Subject of Research: The potential impact of declining fertility rates on future new cases of hereditary angioedema

Article Title: Would the number of new cases of hereditary angioedema decrease due to declining fertility rates?

Article References: Wong, L., Kim, H., & Kuprowski, M. (2026). Would the number of new cases of hereditary angioedema decrease due to declining fertility rates?. Allergy, Asthma & Clinical Immunology, 22(1), Article 45. https://doi.org/10.1186/s13223-026-01056-8

Image Credits: AI Generated

DOI: 10.1186/s13223-026-01056-8

Keywords: hereditary angioedema, fertility rates, SERPING1, C1 esterase inhibitor, rare diseases, autosomal dominant inheritance, demographics, population decline, complement dysregulation, clinical planning, number, cases