FARGO – Karen Daggett was enjoying a five-course Valentine's Day dinner with friends when she suddenly felt her heart beating erratically and her vision clouded.

"Something is really wrong," she told her husband during the salad course. "We need to go to a hospital."

Fog shrouded the road, but the Frazee, Minn., couple found the hospital in Naples, Fla., where they were vacationing. Once in the emergency room, she was unable to provide her birthdate.

Despite the obvious urgency of her medical plight, Daggett had no inkling that the unnerving episode would reveal a hidden health complication that runs rampant in her family.

After being given intravenous fluids, and told to drink something "as fast as you can," Daggett was able to recall her birthdate.

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But the doctors were unable to diagnose the cause of her problem during a five-day hospital stay. When discharged, she was advised to get to the Mayo Clinic, and soon - no later than 48 hours.

There, following a barrage of tests, a process of elimination pinpointed her problem: Daggett lacked a gene allowing her liver to metabolize a long list of medications.

It turned out she became dangerously dehydrated, apparently because her body went haywire after receiving medications for a heart procedure a couple of months earlier. She had critical levels of potassium, magnesium and calcium.

Drugs that aren't metabolized can accumulate in the body, sometimes reaching harmful levels.

"You become toxic and eventually all the organs start shutting down," Daggett said. "I'd be dead without Mayo."

Gene issue affects many

The revelation six years ago that Daggett's liver lacked an important protein enzyme to enable her to metabolize many medications since has rippled through several generations of her extended family, originally from Lake Park, Minn.

So far, 15 family members - including all five of her siblings - have been found to lack the important enzyme and two of her friends also have been found to have the condition, which is more common in those with Scandinavian and northern European ancestry.

"Those who have been tested have it," said Daggett's younger sister Janee Nelson, who lives in Lake Park. "There have been several who haven't been tested."

Having the diagnosis, made available through genetic testing, helped explain medical problems that for years plagued Daggett, her siblings and other family members.

Problems with irregular heartbeat are pervasive in the family, for example. So is the ineffectiveness of many painkillers, a complication that afflicted Daggett and her siblings.

Another sister, Susan Bertelson of Brookings, S.D., recalls experiencing a lot of pain during childbirth when she was younger.

"They were pumping me with stuff," she said, referring to pain medication. "Things just weren't working."

Once, Bertelson woke up during surgery. "I just said 'ouch,' " she said. "You wake up because it hurts."

Those who have the genetic mutation lack an important liver enzyme. They cannot metabolize acetaminophen, the active ingredient in Tylenol, for instance, and Daggett had adverse reactions to blood pressure medications until testing led her to a safe pill.

When the body doesn't properly absorb medications, they can accumulate in high levels and become toxic. Daggett's daughter once was given a high dose of Tylenol, and it almost killed her, she said.

In the case of Daggett and her sisters, it wasn't until they got older and confronted more health issues that the complications from the mutation became glaring.

By one estimate, 7 percent of whites and 2 percent to 7 percent of blacks are poor metabolizers of drugs that depend on an enzyme called CYP2D6 - the enzyme Daggett and her siblings lack altogether - a pathway that metabolizes antidepressants and opioids. That enzyme is involved in metabolizing up to a quarter of all drugs.

Similarly, one in five Asians is a poor metabolizer of drugs that depend on the enzyme CYP2C19, needed to metabolize the anti-seizure medication Dilantin, the sedative phenobarbital and Prilosec, used to treat frequent heartburn, among other drugs.

"Most people don't have a problem until they start a medication," Daggett said. "It's a very interesting adventure. I've almost died a couple of times."

'Knowledge is power'

A mental alarm started clanging when Daggett was awakened by the knowledge that she had inherited the genetic mutation. If she had it, other members of her family could be at risk.

Armed with information, she learned that the problem had been discovered only a few years before her diagnosis, by doctors at Mayo Clinic who learned that some women were unable to metabolize tamoxifen, an antiestrogen drug that is a mainstay in treatment of breast cancer.

Mayo researchers determined that those women would not be protected against the recurrence of the cancer and therefore should not take the drug - information that was especially of interest, since her sister Susan was diagnosed with breast cancer two weeks after Daggett learned she had the genetic variance.

Bertelson had DNA testing and learned that she, too, had the variance. As a result, her treatment did not include tamoxifen; she has not had a recurrence of her cancer.

"Knowledge is power," Daggett said.

Upon hearing that two of her sisters had the troublesome gene variance, Nelson immediately went in for testing, and learned that she also did.

Subsequent genetic testing has found that the variance has been found in four generations of the Nelson family - including both of the siblings' parents, now deceased.

Interestingly, three of the siblings' sets of great-grandparents came from the same village in Sweden, Appelbo, about 200 miles northwest of Stockholm. That might help to explain why the variance is so prevalent in the family, the sisters said.

Testing more common

At first, few of their health providers knew about how the missing enzyme could complicate their medical care. But in the years since, as the emerging field of pharmacogenetics has grown and become better known, physicians are more familiar with it.

Still, navigating a treatment course in a way that avoids adverse drug interactions, therapeutic failure or toxicity can be complicated, the sisters said.

"Our pharmacists are our best friend at this point," said Daggett, who once carried a list of all the medications she can't take to present to doctors unfamiliar with her condition.

Now, the sisters said, because the variance is becoming better known, health providers are better versed in how people lacking important enzymes might react to certain medications.

Clinical genetic testing is also becoming more common, including Sanford's Imaginetics program, Daggett said.

There are more than 50 of the CYP450 enzymes, but six enzymes metabolize 90 percent of drugs, according to a study. Some medical centers now routinely test heart patients for the enzyme, she said.

The Nelson sisters are telling their story in the hope that others who have had similar problems with medications might be prompted to seek testing to determine if they lack important enzymes.

"This discovery has covered four generations of my family and I am only sorry that we weren't able to help my parents in their end-of-life transitions, but we just didn't know," Daggett said.

Anyone suspecting they might have a problem metabolizing medications should seek answers from medical professionals - and be persistent, if necessary, Nelson said.

"Be your own advocate," she said.

Meanwhile, Daggett just celebrated her 70th birthday, a milestone she easily could not have lived to see.