Despite multiple swelling attacks, HAE diagnosis delayed for children

Most took median of 3 years, even though there was family history of disease

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
Children hold hands and form a line.

Children with hereditary angioedema (HAE) may have dozens of swelling attacks until they receive a correct diagnosis of the disease, according to a study in a hospital in Turkey, where the median delay was three years.

“Awareness of the symptoms of HAE is necessary and correct diagnosis is essential to proper treatment,” the researchers wrote in “Clinical Evaluation of Pediatric Patients with Hereditary Angioedema,” which was published in The Tohoku Journal of Experimental Medicine.

People with HAE have sudden, but temporary swelling attacks that affect the deeper layers of the skin and usually appear on their own, without urticaria (hives) or a rash. These attacks can first occur at any age, but usually start in childhood.

Unlike adults, children with HAE can have subtle swelling attacks that overlap with other diseases, making it hard to diagnose them early. A missed diagnosis can cause delays in getting treatment, often leading to painful episodes.

For many patients, “the clinical course of the disease worsens during adolescence,” but not many studies have described the characteristics of HAE in children, leading researchers to collect data from a single hospital in Turkey.

Recommended Reading
In this case study illustration, doctors hold a giant magnifying glass in front of a patient who has red spots on his face and neck.

Case study showcases difficulty with angioedema diagnosis

Reaching a HAE diagnosis

The study included 32 children (16 boys, 16 girls) of a mean age of 9.9 who had their first symptoms when they were a median age of 6. At the onset of the disease, swelling attacks happened mainly in the hands (32.3%), abdomen (32.3%), face (25.7%), and feet (9.7%).

The children had a mean of 38.2 swelling attacks every year. While most (90.6%) had a history of angioedema in the family, it took them a median of three years to be diagnosed with HAE. At the time of diagnosis, they’d had a median of 70 swelling attacks total.

Although none of the children had a skin rash during the attacks, nearly half of them (46.9%) had a tingling sensation in the swollen area, called formication. Itching, or pruritus, was reported by two (6.2%) children.

HAE is caused by mutations that lower the levels of a protein called C1 inhibitor or cause it to malfunction. Without C1 inhibitor, excess fluids leak from blood vessels and builds up in surrounding tissues, leading to swelling episodes.

All but five children (15.6%) had low levels of C1 inhibitor in the blood. In the five children whose C1 inhibitor levels were within the normal range, the protein’s activity was low.

Four different mutations were revealed through genetic testing in SERPING1, the gene that’s faulty in people with HAE types 1 and 2. One mutation, present in three members of a family, had never been reported before and was deemed to be of “uncertain significance,” meaning its disease-causing potential was unknown.

The other three mutations were deemed likely to cause disease and were already linked to HAE. The most common of the three was c.1033G>T (p.Gly345Trp), which was found in 16 members from five different families.

“The diagnosis of HAE is often made after recurrent angioedema attacks because it is not routinely diagnosed due to the rareness of the disease,” wrote the researchers, who said their findings illustrate the importance of raising awareness to emergency physicians and family practitioners about this disease, since they serve as primary health care.”