An estimated 300 children in the United States have Niemann-Pick disease type C, a rare cholesterol disorder that is always fatal.
By a cruel quirk of fate and genetics, three of those children belong to Cindy and Mike Parseghian.
The Tucson couple had never heard of the debilitating disease before. And when they learned in 1994 that all but one of their four children had it, Cindy said, "we were devastated."
But they were not defeated.
With the help of the children's grandfather, Ara, a well-known former football coach at the University of Notre Dame, they formed the Ara Parseghian Medical Research Foundation to battle the genetic disorder.
Research supported by the $6 million they have raised so far played a key role in the announcement in July that federal researchers had identified the defective gene that causes Niemann-Pick.
Discovering the gene will make it possible for the first time to identify carriers who can pass the gene on to their children. Eventually, it will probably lead to new treatments.
But the impact will probably be felt well beyond the small number of families with a history of Niemann-Pick. The newly discovered gene apparently plays a key role in the movement and storage of cholesterol within individual cells--a subject about which researchers previously knew almost nothing. As scientists unlock its secrets, they expect to gain crucial new information about the genesis of heart attacks and strokes.
"By understanding this gene, we not only take a crucial step forward in understanding this devastating disorder, but we also gain insights into problems that affect every one of us," said Zach W. Hall, director of the National Institute of Neurological Disorders and Stroke.
For the Parseghians, however, the discovery is bittersweet. They learned about it shortly after their son Michael died March 22, four days shy of his 10th birthday.
Any new treatments resulting from the discovery are unlikely to be available in time to help his sisters Marcia, 8, and Christa, 6.
"This is a race against time," Ara Parseghian said.
How Disease Takes Its Toll
Niemann-Pick type C is a disorder in which low-density lipoprotein, the so-called bad cholesterol, accumulates in and eventually destroys cells of the brain, liver, spleen, lungs and bone marrow.
Cholesterol--a fat--is a component of cell membranes and an essential building block for steroid hormones. But too much of it can lead to clogged arteries, atherosclerosis and heart attacks.
Children with the disease often have jaundice at birth or shortly thereafter. As they near school age, they tend to develop an unsteadiness in walking, difficulty in controlling their limbs and problems in moving their eyes. As it progresses, they have difficulty with all forms of mental functioning and develop slurred speech. Death is caused by failure of one or more organs.
About 1 in 1 million children is born with the disease. It is a recessive genetic disorder, meaning that a child must inherit a copy of the defective gene from both parents to develop the disease.
If both parents carry the gene, as is the case with Cindy and Michael, each child's odds of having the disease are 1 in 4. The odds that three children in the same family will have the disease are 1 in 64.
In Hollywood terms, Mike and Cindy met cute. Students at Notre Dame, where Mike played football for his father's Fighting Irish in 1974, they studied in the same section of the library, lived in the same dorm and ate in the same dining hall. Eventually, Mike asked Cindy out and they married after graduation, he with a degree in premed, she in accounting.
After medical school at Northwestern, the couple moved to Tucson, where Mike took up practice as an orthopedic surgeon. In 1984, Ara, named after his famous grandfather, was born.
The first hint of a problem in Michael appeared when he entered kindergarten. He was clumsy, although not more than other children in the class.
"But in kindergarten," Cindy recalled, "the others started progressing, while Michael kind of stagnated."
The family pediatrician "gave Michael three small tests but found nothing. "He said, 'If it was my child, I wouldn't do anything,' Cindy recalled. "But we just knew in our hearts and souls that something was wrong."
They went to other doctors, but the results were much the same. Some said he suffered from cerebral palsy, others said they simply had no idea. Finally, after 16 months of doctor-hopping, physicians at Columbia University in New York City diagnosed his condition as Niemann-Pick type C, commonly called NPC.
The physicians had access to all of Michael's previous tests, but the big clues, they told Mike and Cindy, were his eye movements and his enlarged spleen.
"As soon as they said that, our hearts went down to our toes because the two girls also had enlarged spleens," Cindy said. "You can imagine the impact it had on us. The burden of having one child with it and compounding that with two more was just unfathomable."