BackgroundHereditary angioedema (HAE) is a rare and life-threatening inborn error
of immunity. HAE is mostly caused by pathogenic variations in the serine protease
inhibitor gene 1 (SERPING1), leading to deficient or dysfunctional C1-inhibitor (C1-INH),
overproduction of bradykinin, and development of recurrent subcutaneous and/or submucosal
oedema. The prevalence of HAE is 1 in 50,000 - 100000 people worldwide. We aimed to
describe the clinical features and genetic spectrum of hereditary angioedema with
C1-INH deficiency (C1-INH-HAE) in Latvia.MethodsAll patients from Latvia diagnosed
with HAE (types I/II) from 2006 to March 2022 were included in the study. Laboratory
tests and clinical data were analysed, and genetic tests with Sanger sequencing and
whole genome sequencing were performed.ResultsThe study identified 10 C1-INH-HAE patients
(nine females, one male) from eight families. The point prevalence of HAE in Latvia
is 0.53 per 100 000 inhabitants. Of all patients, seven (70%) had HAE type I and three
(30%) had HAE type II. The median age of patients was 54 years and the median age
at onset of symptoms was 15 years. A significant delay (median 20.5 years) until diagnosis
was observed, and 60% of patients had a positive family history of angioedema. All
HAE patients have been hospitalised a median two times during their lifetime. Skin
(100%), abdominal (80%), and airway (80%) oedema were the most frequent symptoms.
Triggering factors (60%) and prodromal symptoms (90%) were referred. Attacks were
severe in 50% of patients, moderate in 10%, and mild in 40%. Pathogenic variations
of SERPING1 were identified in eight patients (six families), confirming the diagnosis
molecularly. In two patients (two families), no pathogenic variations in the genes
were found even after whole genome sequencing.ConclusionsCurrent data shows a significant
delay and clear underdiagnosis of HAE in Latvia. Higher awareness and better information
and communication between doctors would improve the diagnosis and management of HAE;
as would screening of family members, patients with recurrent angioedema unresponsive
to antihistamines and glucocorticoids, and patients with recurrent episodes of severe,
unexplained abdominal pain.
