Recurrent angioedema with normal C1-inhibitor: genetics determine the endotype

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Abstract

Hereditary angioedema with normal C1 esterase inhibitor is a rare genetic disorder characterized by periodical and unpredictable angioedema without quantitative and qualitative deficiency of C1-inhibitor. According to the modern classification, this disease can present as two different endotypes: bradykinin-mediated and endothelium dysfunction-associated. Diagnosis of this disease is complicated by the need to perform genetic screening because available laboratory tests (C1-inhibitor, its functionality, and C4 protein in blood plasma) are within normal values, functional molecular tests are not available, clinical data are limited to few cohorts and, for some genetic defects, to single clinical observations. Genetic examination of patients with recurrent angioedema expands the cohort of patients with hereditary angioedema and normal C1 esterase inhibitor.

The article describes 17 patients with hereditary angioedema with normal C1 esterase inhibitor who underwent treatment at a specialized center in Moscow. The bradykinin-mediated angioedema endotype was found in 13 patients (9 with mutation in PLG, 2 with mutation in FXII, and 2 with mutation in KNG1), and endothelium dysfunction-associated angioedema was diagnosed in 4 patients with mutation in MYOF (2 asymptomatic carriers). Currently, data on the clinical presentation, diagnosis, and therapy of patients are limited to single clinical cases and small clinical case series, thus further data collection is needed.

The publication contains unique data on the algorithm of diagnosis and selection of therapy in patients with angioedema and normal C1-inhibitor level.

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About the authors

Marina S. Lebedkina

Moscow City Hospital 52

Author for correspondence.
Email: marina.ivanova0808@yandex.ru
ORCID iD: 0000-0002-9545-4720
SPIN-code: 1857-8154

MD

Россия, Moscow

Darya S. Fomina

Moscow City Hospital 52; The First Sechenov Moscow State Medical University (Sechenov University); Astana Medical University

Email: daria_fomina@mail.ru
ORCID iD: 0000-0002-5083-6637
SPIN-code: 3023-4538

MD, Cand. Sci. (Med.), Assistant Professor

Россия, Moscow; Moscow; Astana, Republic of Kazakhstan

Elena N. Bobrikova

Moscow City Hospital 52

Email: elena.bobrikova.69@mail.ru
ORCID iD: 0000-0002-6534-5902
SPIN-code: 5806-7260

MD

Россия, Moscow

Yulia D. Yukhnovskaya

Moscow City Hospital 52

Email: yukhyuliya@yandex.ru
ORCID iD: 0000-0002-0928-2054
SPIN-code: 1688-2416
Россия, Moscow

Anna A. Roppelt

Moscow City Hospital 52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-5132-1267
SPIN-code: 7249-4423

MD, Cand. Sci. (Medicine)

Россия, Moscow

Tatyana S. Kruglova

Moscow City Hospital 52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-4949-9178
SPIN-code: 2884-5000

MD, Cand. Sci. (Medicine)

Россия, Moscow

Olga A. Mukhina

Moscow City Hospital 52

Email: mukhina.o.a@gmail.com
ORCID iD: 0000-0002-3794-4991
SPIN-code: 7721-1941
Россия, Moscow

Ulyana A. Mаrkina

Moscow City Hospital 52

Email: itcher.md@bk.ru
ORCID iD: 0000-0002-6646-4233
SPIN-code: 6424-0012
Россия, Moscow

Ekaterina A. Nikitina

Moscow City Hospital 52

Email: katrin88866@gmail.com
ORCID iD: 0000-0002-0865-8355
SPIN-code: 3507-9106
Россия, Moscow

Yulia G. Alekseeva

Moscow City Hospital 52

Email: doctorajg5@gmail.com
ORCID iD: 0000-0002-4131-2436
SPIN-code: 5379-3655
Россия, Moscow

Aleksandr V. Karaulov

The First Sechenov Moscow State Medical University (Sechenov University); Life Improvement by Future Technologies (LIFT) Center

Email: drkaraulov@mail.ru
ORCID iD: 0000-0002-1930-5424
SPIN-code: 4122-5565

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Skolkovo

Mariana A. Lysenko

Moscow City Hospital 52; The Russian National Research Medical University named after N.I. Pirogov

Email: gkb52@zdrav.mos.ru
ORCID iD: 0000-0001-6010-7975
SPIN-code: 3887-6250

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Moscow

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