Toddler will help study rare disorder

By DAVE KOLPACK
Associated Press
FARGO, N.D. - Gretchen and Mark Noah have big plans for their son, Markie. In their hearts, they know he will make a difference in the world, that he will do great things.
For now, they're happy to hear him laugh and see him act like a rambunctious 3-year-old, riding around on his bright green tractor with yellow trim or getting into scuffles with his four sisters.
The Noahs knew early on that their boy was different. Special.
He couldn't sit or crawl. He was so sensitive to sounds he covered his ears during his sisters' hockey games. He would push the same button on his tractor over and over. It would play the theme from Green Acres. Over and over. While children his age could say one or two words and understand simple instructions, Markie was lost in silence.
Not until last spring was Markie diagnosed with Smith-Lemli-Opitz syndrome (SLOS), an inherited metabolic disorder that blocks the body's ability to produce cholesterol. It's commonly characterized by malformations of the heart, lungs, kidneys and gastrointestinal tract. Children have developmental disabilities, behavioral issues and, in the most severe cases, profound mental retardation.
It has no known cure, but there are treatments to relieve some of the symptoms and disabilities.

"Mark Christopher Noah. Healthy Baby! 6lbs 7oz" Nov. 12, 2003.

For the first year in her son's life Gretchen Noah kept a diary, recording on a calendar the milestones that marked his progress.
His baptism. His first bath. His first taste of solid foods - green beans. A drink of water from his first sippy cup. And on May 21, 2004, his first tooth, "ta-da!"
But tucked between those signposts were worrisome problems.
A day after Markie was born, the obstetrician discovered he had a heart murmur. It shouldn't cause any serious problems, doctors reassured the Noahs. Markie also had a small head, an upturned nose, a droopy left eyelid, and a dwarfed thumb and index finger on both hands.
There was more. He had trouble nursing. He had chronic ear infections. In his first month, for five days in a row, he couldn't sleep and developed colic - that inconsolable crying spell. He didn't babble like a typical baby. He grunted.
The Noahs attended to each illness, unaware that collectively they were an alarm bell for the mental and physical disabilities of the rare hereditary disorder.
Markie first started to communicate with sign language, learning signs for apple, cookie or candy. Later, he used the word "bah" to refer to most items in the house.
"We didn't know if he would ever talk," Gretchen Noah said.
At about 14 months, the Noahs enrolled him in physical, occupational and speech therapy at Pediatric Therapy Partners, a children's clinic in Fargo. There was no emotional connection between the patient and his therapists. They spent hours teaching Markie how to pinch a Cheerio between his thumb and index finger.
"Everything was a struggle for him," therapist Stephen Olson said.
A geneticist at the University of North Dakota suggested Markie that could have SLOS, but the doctors the Noahs saw couldn't confirm it. Gretchen Noah pursued the idea on the Internet after talking to a mother she met at a support group for children with heart defects.

"I worry for you. I never want you to be teased or feel different. I want you to be healthy and happy." Jan. 19, 2004.

Smith-Lemli-Opitz syndrome was first described by geneticists David Smith, Luc Lemli and John Opitz in 1964, but it was not until 30 years later that scientists discovered that children with SLOS were unable to make or process cholesterol.
As a result, they have distinctive physical features, including a cleft palate, low-set ears, a single palm crease, webbing between the second and third toes and some types of genital malformations. A majority of patients have autistic characteristics - they can't maintain eye contact; they avoid showing affection.
Dr. Forbes Porter, Markie's physician and a researcher with the National Institutes of Health, said about 80 percent of SLOS pregnancies never survive to a full term. More than half of the children with the syndrome must be tube-fed for several years.
The disorder affects as many as 1 in 40,000 births and is most common in whites of European ancestry.
Markie's case is rare because it's mild.
Before giving birth to Markie, Gretchen Noah had six miscarriages. The Noahs since have learned that their genetic combination led to the disorder and the miscarriages.
Markie's oldest sisters - Margaret, 9, and Kelly, 8 - have tested negative for the disorder; since 5-year-old Mary and Katherine, 18 months, show no signs or symptoms of the disorder, their parents say they can get tested when they're older to learn whether they are carriers of the altered gene.
"We've gone through six miscarriages, so obviously we're not in charge," said Mark Noah, a physical therapist for a nursing home.
Except for the heart condition, Markie's major organs function normally.
Without his medication, though, he will harm himself - uncontrollably biting his shirt collars and slapping himself in the head with both hands, much like the autistic savant Dustin Hoffman played in Rain Man. During temper tantrums, he throws himself on the ground. These behaviors are associated with abnormal cholesterol metabolism.
Only about 500 people in the United States are living with the disorder, which is commonly misdiagnosed, Porter said.
For women who suspect they are at risk of carrying the altered gene, a prenatal blood test can measure an enzyme important for the body's production of cholesterol. One problem caused by a lack of the enzyme: Potentially toxic byproducts from cholesterol production build up in the blood and other tissues, according to the Genetics Home Reference Web site of the National Institutes of Health.

"I just know that you are going to change the world. I tell you all the time that you are going to cure cancer ... or make a difference ... or save a life ... or help the needy. You will do great things! God's work. I'm sure of it."

Gretchen Noah made the journal entry on March 31, 2004, when her son was 4 1/2 months old - a full two years before he was diagnosed with Smith-Lemli-Opitz syndrome. It seems prophetic.
Because Markie's case is so mild, Porter believes he makes an ideal candidate for studying the genetic mutations and characteristics of SLOS. How he responds to medication could affect the lives of other children with more severe forms of the disorder and more common ones such as autism.
Porter is treating the learning and behavior problems by trying to correct the biochemical defect in the brain. For the past six months, Markie has been taking three spoonfuls a day of a cherry-flavored cholesterol serum, a standard treatment.
It has made a vast improvement in Markie's speech and behavior, his mother said.
For one, he doesn't have tantrums anymore.
"Out Mama," he tells Gretchen Noah when he wants to be removed from his crib. "Oh, thank you, Mama," he says after she lifts him out.
Shown a picture of a parrot, he says, "Tah-rock-er-ah-pirt." That means "tropical bird," his mom says.
Markie no longer is enrolled in physical therapy but twice a week, he works on flexibility and strength in his hands, and is learning to use a pair of scissors. He's no longer oblivious to everyone in the room.
"Now he has blossomed into this little boy who is active and runs and plays and laughs and jokes and all those kinds of things," Olson said.
Porter says Markie will always have some degree of learning and behavioral problems, but he should have a normal life expectancy.
Mark and Gretchen Noah have hope, and they plan to enroll Markie in preschool next year.
 

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