Management of hereditary angioedema type I and homozygous MTHFR mutation during pregnancy

ABSTRACT

Hereditary angioedema (HAE) is an autosomal dominant disease, characterized by edema attacks resulting from quantitative and/or functional deficiency of the C1 inhibitor (C1-INH), which acts in controlling the complement, coagulation, fibrinolysis, and contact systems. The exacerbation of these systems results in decreased circulating levels of kallikrein and conversion of bradykinin. In addition, thrombophilia is related to the deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme, causing an increase in homocysteine, accumulation of atheromatous plaques, and arterial and venous thrombosis. The association of these conditions in related systems brings greater clinical risks to the patient. We report a female patient, aged 23 years, with HAE and homozygous MTHFR mutation, G2A1, carrier of HAE with crises since early childhood. The first pregnancy terminated with abortion due to gestational sac detachment. In the second pregnancy, at 5.1 weeks, she had bleeding and partial detachment of gestational sac. Thrombophilia tests confirmed homozygosity for the MTHFR enzyme. At the beginning of gestation, she had attacks of angioedema treated with fresh plasma, and at one occasion, she received treatment with a plasma-derived C1-INH esterase. During breastfeeding, she received prophylaxis with plasma-derived C1-INHdp. The course of HAE during pregnancy worsened. There are studies that discuss the occurrence of abortion due to attacks of angioedema. The patient’s disease was associated with a homozygous MTHFR mutation, which probably caused the miscarriage. The control of both clinical situations is important for the success of pregnancy, so a combined action plan between obstetricians and HAE treatment specialists is essential (AU)