Hereditary Angioedema (HAE) with a mutation in the plasminogen gene: a retrospective study of a cohort of 14 patients from Russia

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Abstract

BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency — hereditary angioedema with a mutation in the plasminogen gene — was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant.

AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II.

MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.64±13.55 years) with hereditary angioedema with c.988A>G mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.03±16.23 years).

RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.07±10.46 years, which is significantly higher than in patients with hereditary angioedema type I/II — 11.58±8.92 years (p <0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p <0.001; abdominal attacks 86.6%, p <0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II (p=0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid.

CONCLUSIONS: The disease’s manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.

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About the authors

Irina A. Manto

National Research Center – Institute of Immunology Federal Medical-Biological Agency

Author for correspondence.
Email: irina.manto@yandex.ru
ORCID iD: 0000-0001-6432-394X
SPIN-code: 7944-5159

MD, Cand. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Elena A. Latysheva

National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia; Pirogov Russian National Research Medical University

Email: ealat@mail.ru
ORCID iD: 0000-0002-1606-205X
SPIN-code: 2063-7973

MD, Dr. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; 1, Moskvorechye str., Moscow, 115578

Elena A. Bliznetz

Federal State Budgetary Institution, Research Centre for Medical Genetics

Email: bliznetzelena@mail.ru
ORCID iD: 0000-0002-5339-5566
SPIN-code: 8451-3075

Cand. Sci. (Med.)

Russian Federation, 1, Moskvorechye str., Moscow, 115578

Daria O. Timoshenko

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: d.o.timoshenko@gmail.com
ORCID iD: 0000-0002-7585-1390
SPIN-code: 2714-0906

MD

Russian Federation, 1, Ostrovityanova, Moscow, 117997

Liubov V. Aleshina

Saratov State Medical University named by Razumovsky

Email: Lubov-sk@mail.ru
ORCID iD: 0000-0002-3281-7379

Cand. Sci. (Med.)

Russian Federation, 22, Proviantskata str., Saratov, 410028

Yulia A. Bocherova

Tambov Regional Clinical Hospital named after V.D. Babenko

Email: dum_spiro.spero@inbox.ru
ORCID iD: 0000-0003-4182-0008
Russian Federation, 29, Moskovskaya str., Tambov, 392023

Elvira R. Gilvanova

Bashkir State Medical University; Bashkir State University; State Medical Institution of the Republic of Bashkortostan City Hospital 2

Email: elvira_rer@mail.ru
ORCID iD: 0000-0002-0188-8625

Cand. Sci. (Med.)

Russian Federation, 3, Lenina str., Ufa, 450008; 32, Zaki Validi str., Ufa, 450076; 59, Patrioticheskaya str., Sterlitamak, 453130

Galina A. Kameneva

Аrkhangelsk Regional Clinical Hospital

Email: gaakam@mail.ru
ORCID iD: 0000-0002-2328-9420
Russian Federation, 292, Prospect Lomonosova, Arkhangelsk, 163045

Maria A. Platonova

Laboratory MedLab

Email: drmaria65@mail.ru
ORCID iD: 0000-0001-9669-8391
Russian Federation, 46, corp. 2, lit. B, Tambovskaya str., Saint Petersburg

Valentina A. Fedorova

Tula Regional Clinical Hospital

Email: valentina1957efanova@rambler.ru

Chief freelance specialist of The Ministry of Health of Tula oblast

Russian Federation, 1a, st. Yablochkova, Tula, 300053

Aleksander V. Polyakov

Federal State Budgetary Institution, Research Centre for Medical Genetics

Email: apol@dnalab.ru
ORCID iD: 0000-0002-0105-1833
SPIN-code: 6453-3097

Dr. Sci. (Bio), Professor

Russian Federation, 1, Moskvorechye str., Moscow, 115578

Tatiana V. Latysheva

National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: tvlat@mail.ru
ORCID iD: 0000-0003-1508-0640
SPIN-code: 8929-7644

MD, Dr. Sci. (Med.), Professor

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; 20/1, Delegatskaya st., Moscow, 127473

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Supplementary files

Supplementary Files
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1. Fig. 1. Current classification of hereditary angioedema.

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2. Fig. 2. Comparative analysis of angioedema localization in patients with hereditary angioedema with C1-inhibitor deficiency (n=194) and HAE-PLG (n=14),%.

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