When she heard her younger son’s quavery cry of “M-o-o-o-m-m-m” drifting down the hall in the middle of the night, Jocelyn Mathiasen stiffened, braced for what lay ahead.
Sometimes the little boy would awaken just before dawn shaky and weak, complaining of hunger or thirst; after consuming something he would quickly recover. But on the bad nights Peter Dawson would spend hours lying on the floor of the bathroom clutching his stomach, vomiting intermittently and refusing to drink anything. It took him hours to rebound — and it was never clear what had made him so sick.
Mathiasen did not know what to make of these episodes, which at first were only mild and infrequent, blips in the life of her otherwise healthy child. But when Peter turned 5 in 2006 and the family moved to Easton, Conn., from Seattle, Mathiasen asked her new pediatrician whether the episodes were normal. Leveling a hard look at her, he told her that what she was describing was definitely not normal — and might signify a serious problem, such as juvenile, or Type 1, diabetes. But after tests for diabetes were negative, the search for the underlying cause of Peter’s odd problem floundered.
It would take nearly five years for a specialist eight states away to figure out what was wrong. The solution was a surprisingly cheap and prosaic remedy — but one that recently drew attention in an airport security line.
As an infant, Peter would periodically wake up in the morning in obvious distress, grabbing his bottle and sucking down the contents “in one gulp, like he was desperate,” his mother recalled.
“I didn’t worry too much about it because it didn’t happen often, and after he ate he seemed fine,” Mathiasen said. For some reason the episodes were worse when the family traveled. Mathiasen said she refrained from mentioning them to his doctor, not wanting to seem alarmist. “I was trying to be this relaxed mother,” she said.
After the test for diabetes was negative, the pediatrician referred Peter to a pediatric endocrinologist in New Haven. Once a tumor and several other disorders had been ruled out, the doctor settled on a diagnosis of reactive hypoglycemia: severely low blood sugar that occurs several hours after eating. She predicted that Peter would outgrow the problem when he hit puberty and recommended that he eat yogurt at bedtime: The protein would be slowly digested and would prevent his blood sugar from plummeting.
By 2007 Mathiasen had become increasingly uneasy. Despite the yogurt, Peter kept having episodes. She began keeping lollipops or Skittles in the house: A rapid hit of sugar seemed to help him recover faster.
After four incidents in four weeks, Mathiasen consulted a second pediatric endocrinologist. He admitted the first-grader to a hospital overnight, hoping to catch an episode, which could provide important clues. Peter underwent hourly checks; although his blood sugar dropped, the readings were not alarming.
When he was discharged the following morning, Mathiasen was told to continue the yogurt regimen; by now he was eating two heaping bowls at bedtime.
“It was a very, very disconcerting experience,” recalled Mathiasen, who had become increasingly convinced that waiting for the problem to disappear was not a solution. In the spring of 2008, Peter had a scary episode on a trip. The family had forgotten his bedtime yogurt, and he awoke shaky and incoherent. His parents gave him a lollipop and bundled him into the car; at the airport he vomited several times, reluctantly ate a cookie and then fell into a deep sleep on the plane. After he woke up he drank six glasses of milk, then seemed fine.
“At that point, I said we really need to figure out what’s going on here,” Mathiasen recalled.
In December 2008, Peter underwent a complete workup with the second endocrinologist, which provided no answers. Mathiasen had been monitoring Peter’s blood sugar when he woke; she found that readings on some days were very high, not low. Because nothing else seemed to fit, the endocrinologist suggested that Peter might have a rare condition: glycogen storage disease (GSD).
The inherited metabolic problem is a constellation of 14 disorders, ranging from mild to life-threatening, that result from the impaired regulation of glycogen, the stored form of glucose, which the body uses for fuel. DNA testing for the disease, which affects about one in 20,000 people, according to Cincinnati Children’s Hospital, had recently become available. The doctor suggested that Peter undergo a test for a mild form of GSD that seemed to fit his symptoms. After several months, the family’s insurance company agreed to pay for it.
Months went by — genetic tests often take a long time — and Mathiasen, who had heard nothing, began calling the doctor. In October 2009, he sent her an apologetic e-mail: The lab had lost the sample before the DNA test could be performed.
“My clinical impression [is] that this glycogen storage disease diagnosis is highly unlikely,” he wrote. He proposed that Peter undergo a procedure to implant a device that continuously monitors glucose levels to see if he might have a rare condition called exercise-induced hyperinsulinism, or low blood sugar after exercise, because some episodes had occurred after skiing.
Mathiasen, who was then spending hours online researching Peter’s symptoms, assisted by a friend who is an endocrinologist in Baltimore, decided that maybe GSD wasn’t so unlikely. The name of one expert kept popping up: pediatric endocrinologist David A. Weinstein, who heads the Glycogen Storage Disease Program at the University of Florida College of Medicine.
One evening in February 2010, Mathiasen sent Weinstein an e-mail. She described Peter’s case and said she’d hit a brick wall. Did Weinstein have any suggestions?
Soon afterward Weinstein called Mathiasen back. He agreed that Peter might have GSD and recommended the family buy a monitor that could check the level of ketones, potentially dangerous substances that can cause nausea and vomiting and, at sustained high levels, death. Ketones, produced when the body uses fat rather than glucose for energy, would be an important clue to a diagnosis; ketotic hypoglycemia is a symptom of some forms of GSD. Testing over the next few months showed that Peter’s ketone levels were sometimes dangerously elevated; his body was literally starving for energy.
Weinstein agreed to accept Peter as a patient and to perform DNA testing. He advised Mathiasen to replace the bedtime yogurt with a drink containing several tablespoons of cornstarch. One of the cheapest ingredients in a supermarket at less than $2 per box, cornstarch provides slow-release glucose. Within weeks, Peter’s episodes largely disappeared.
In June 2011, after the first DNA test proved to be negative, Peter and his mother flew to Florida to see Weinstein, who observed Peter having an episode in the hospital. Peter was then tested for two other generally mild forms. Six months later, just as the family was departing for a holiday trip, Weinstein called with the diagnosis that had taken five years: Peter’s DNA test revealed he had a type of GSD that is caused by a deficiency in the liver enzyme phosphorylase kinase.
GSD has received scant attention and is, in Weinstein’s view, underdiagnosed; in part, this is because there is little incentive to develop sophisticated treatments, since cornstarch has proven effective for certain forms of the disease if detected early enough. “One of the problems we’ve had is that treatments are not fancy — cornstarch is a gravy thickener,” observed Weinstein, who said his program has treated 400 children from 31 countries and nearly every state. “Most people feel that if we’re not treating it with a fancy medication, it’s not a real medical condition,” and in some cases schools don’t take it seriously.
Although Peter’s type of GSD tends to be mild and can be controlled with a combination of careful monitoring, a high-protein diet and cornstarch, Weinstein said he has seen babies who needed liver transplants. “There’s a variability we don’t quite understand” in the severity of the disease.
Peter, who will soon turn 11, has been told that when he is older he must completely abstain from alcohol, because it could damage his liver. He takes cornstarch dissolved in a drink at bedtime every night and also during the day if he is especially active. And he always travels with several boxes of the cheap white powder and a scale to measure it. For children who travel by air, the cornstarch regimen can raise questions. Recently, Mathiasen said, her family was stopped at a New York airport, where airline security guards tested Peter’s cornstarch. (Weinstein said he offers patients a letter explaining the therapy.)
The strange, shaky episodes are a thing of the past, and Peter is living a normal life. “Now I know what’s wrong, how to treat it, what’s going to happen next and I have a doctor to call,” Mathiasen said. “It’s such a relief.”