Child diagnosed with HAE, despite normal C1-INH: Case report

Girl was diagnosed with rare subtype with normal protein levels, function

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A 2-year-old girl with Down syndrome who was diagnosed with a rare form of hereditary angioedema (HAE) was the subject of a case report by researchers in Palestine.

The child’s case was detailed in “Hereditary Angioedema With a Normal Complement Level,” which was published in Cureus.

Most instances of HAE are caused by mutations that disrupt the production or activity of C1 esterase inhibitor (C1-INH), a protein that blocks the activity of other proteins that promote the signaling molecule bradykinin’s production.

Bradykinin causes blood vessels to widen, which increases their permeability and lets fluid leak out into nearby tissues. This can cause swelling attacks that can arise rapidly in any part of the body.

Another feature of the disease that occurs as a consequence of low C1-INH activity is low levels of C4, a protein of the complement cascade, which is part of the immune system.

Here, researchers describe the case of a Palestinian girl with Down syndrome who developed HAE, but had normal C1-INH.

The girl was brought to the emergency room (ER) due to swelling in her lips and tongue after she ingested ground pepper. She had no history of food or drug allergies and had never had an episode like that before.

She was given dexamethasone and the antihistamine chlorpheniramine maleate, which led to some improvements. She was discharged with a prescription of oral dimetindene, another antihistamine.

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Reaching a diagnosis

The swelling worsened the next day and was accompanied by mild tachypnea, a condition marked by rapid breathing. She was brought again to the ER where her vital signs were stable. The girl was conscious, but irritable.

She again received chlorpheniramine maleate and two doses of adrenaline and dexamethasone, which were administered via an injection under the skin.

The girl showed no improvement, however, and was transferred to the pediatric intensive care unit (PICU), with her physicians suspecting HAE. As the swelling worsened, she was intubated and kept on assisted breathing for three days.

Her vital signs were normal after she was removed from assisted breathing. An examination showed normal breathing and heart sounds, but she still had swelling in the face, lip, and tongue, accompanied by redness.

Blood work in the PICU revealed signs of generalized infection, or sepsis, for which she started intravenous (into the vein) treatment with the antibiotic ceftriaxone. Her blood was positive for the bacteria Streptococcus pyogenes and an echocardiogram showed trivial tricuspid regurgitation, which happens when blood flows back into the heart’s right upper chamber due to a valve malfunction, consistent with the ongoing infection.

More lab work revealed normal C1-INH and slightly elevated C4 levels, which indicated a rare HAE subtype where C1-INH levels and function are normal.

“This case illustrates hereditary angioedema presenting with a normal complement level, especially C1-INH levels and function. Physicians often use the complement level to diagnose HAE, causing a diagnostic dilemma for cases like ours,” the researchers wrote.

The girl was given fresh frozen plasma infusions every eight hours. She also received red blood cell transfusions and her DNA was collected for genetic analysis.

She was referred to a pediatric immunologist and treatment with Cinryze, an approved therapy to prevent HAE swelling attacks, was deemed necessary. That therapy was unavailable, however, so she was transferred to another medical facility.

“Although there are currently no approved treatments, positive responses have been seen to her use of C1-INH concentrate and tranexamic acid to alleviate both immediate and delayed symptoms,” wrote the researchers, who said the case presented “an opportunity to explore potential genetic factors contributing to the patient’s condition.” They called saving a DNA sample for “possible genetic workup” a forward-thinking way toward “understanding the underlying mechanisms of angioedema in this context.”