She called her mother. What have birth control pills done to you? She asked. It was horrible, said her mother, and it took months to find out. The first attack was just days before their wedding. She started taking birth control pills weeks earlier so she wouldn't have to worry about getting pregnant during her honeymoon. One morning she woke up with a terrible stomachache. Her father had to carry her to the car to take her to the hospital. The doctors there couldn't go wrong. A day later, she started feeling better. But it kept happening and no one could figure out what was going on.
After months of these seizures, she found that they started after she took the pill and stopped taking it. And miraculously the pain stopped. Recently, her mother added, the patient's cousin had the same pain after starting the pill. So maybe it runs in the family.
Another blind alley
The patient told all of this to Budhraja's partner, who looked after her during this hospital stay. It was a compelling story, the doctor agreed. She ordered the HAE test and warned the patient that it could be days before he comes back. In the meantime, they could help her with the pain and make sure nothing else was going on.
HAE is an inherited imbalance in the complex chemical systems that control swelling and inflammation. Most people with HAE make insufficient or ineffective amounts of C1, a protein that blocks swelling and inflammation. If the patient has too little C1, it is HAE type 1. If there is enough C1 but not working, then the patient has HAE type 2. The patient went home the following day after the pain subsided and was excited Having found cause for her in pain. But when Budhraja saw the results of her test, he was surprised. Your C1 was completely normal. If she didn't have HAE, what did she have?
Rare variant of a rare disease
Budhraja quickly turned to an online medical resource called UpToDate. In the article on HAE, there was a single paragraph entitled "HAE with Normal C1". Budhraja was relieved to see that such a thing existed. New research, he read, showed that there are many genetic abnormalities that can cause HAE, and while most affect C1, others don't. The most common of these rarities mainly affects women, usually causes swelling of the intestines, and is often triggered by exposure to estrogen during pregnancy or after starting birth control pills. The doctor couldn't believe his luck. This newly described disorder, HAE 3, seemed a perfect fit for his patient and her family.
Most people with this rare variant of this rare disease have an abnormality in the gene that makes factor XII part of the machinery that causes blood to clot. How exactly this defect causes the swelling is still unclear. The only way to test this is to look at the gene that codes for the factor XII protein. It took another six weeks for that answer to come back: She had HAE 3. And one of her daughters and probably her mother too.
There is no cure for this disease, but medications exist that can stop an attack once it starts. The patient now has this medication – just in case. She has taken a closer look at her family background and believes that many of the women on their mother's side had this disease and some may have died from it. She is grateful to Budhraja for making this diagnosis. The doctor sees it differently. "I'd like to get credit for that," he told me. “Really I would. But it was the patient – she did it. "