D3.55 - Hereditary angioedema with normal C1-INH: DAB2IP mutation report

Rational: [MOU1] 

Hereditary phenotypes of recurrent angioedema with normal C1 Inhibitor (HAE-nC1-INH) is a rare genetic disorder characterized by periodic and unpredictable [MOU2] angioedema (AE) without quantitative and qualitative deficiency of C1-inhibitor (C1-INH) and the proven described cases are mostly limited by the absence of functional tests. A missense variant (p.D239N) in DAB2IP was identified in 2024 and for further  sum up process was included to CARE registry.

Family case presentation:

Anamnesis:

A 38-year-old woman considered herself ill since the age of 29, when she has begun to notice the appearance of peripheral AE (hands, forearms, feet, legs) happened weekly during her second pregnancy. The AEs were accompanied by a feeling of tension, absence of itch and burning and resolved spontaneously within 3 days. After giving birth, the AE was not bothersome. During her third pregnancy at the age of 31, she again noted recurrent AE with high frequency (about 1-2 times a week). The use of systemic glucocorticoids (GCS) and antihistamines (AH) didn’t influence the incidence, duration and the severity of the episodes.  There are no precursors and the provoking factors are stress, trauma and pregnancy.

Family history: One of 3 sons is carrying the same mutation in a heterozygous state – all asymptomatic. Her mother and aunt suffer from AEs fron the 3 ^th decade of life, same mutation was detected.

Laboratory findings:

C4 – 0.2 g/l (0.2-0.55)

C1-INH 0.32 g/l (0.23 – 0.41)

C1-INH functional 103% (70-130)

Genetic findings:

Whole genome sequencing: a mutation was detected in the DAB2IP gene cDNA/protein change: chr9:121772792G>A c.226.

Treatment:

Due to the high frequency of AE, tranexamic acid 3 g/day was initiated, but AEs still occur  once a month. Icatibant is used as on demand with the delay in response within 5 hours. Conclusion:

Currently, the evidence-based data for clinical features, diagnosis, genetic findings and treatment relevant to HAE-nC1-INH is limited. Data collection is necessary, especially in the case of rare and new mutations.