09:39 AM EST on Sunday, November 9, 2003

BY KATHERINE BOAS
Journal Staff Writer

NARRAGANSETT -- The yellow corn disappears slowly, one kernel at a time, into Nicholas Hart's mouth. The boy's eyes shift to the toys in the living room. He'd rather play than eat dinner.

He thinks he's had enough corn but his parents disagree. Steve and Geriann Hart spent much of the morning planning, steaming and carefully measuring Nicholas's food. He must finish every kernel.

Nicholas pops up from the table, runs around and then returns. A few more kernels vanish. He pops up again. The amount of corn dwindles slowly. Finally, after an hour and 10 minutes, the bowl is empty.

Despite the antics, the 3-year-old knew from the start he had to finish his meal.

"I have tyrosinemia," he says. The big word rolls off his tongue.

Tyrosinemia is a rare genetic disorder that prevents the liver from producing an enzyme needed to break down the amino acids found in proteins. Left untreated, children with tyrosinemia will develop liver failure or liver cancer, sometimes in days but always within a few years.

Nicholas is the only person in Rhode Island known to have tyrosinemia, his parents and doctors say. His case is reportedly one of fewer than 100 in the country and 300 in the world.

The disease is so rare that many doctors have never heard of it, and most states don't test for it in the womb or at birth. Many babies who are born with signs of tyrosinemia don't live past their second birthdays. Some, like Nicholas, have a chronic form of the disorder that doesn't present itself until they are a few months old.

Journal photo / Connie Grosch Nicholas Hart has a rare liver disease. There's no cure. But the Hart family have learned to cope. Gram by Gram. Meal by meal.

But, with the proper diet and medication, children with tyrosinemia can live relatively normal lives.

WHEN STEVE AND Geriann married in 1995, and even when they had Jessica in 1998 and Nicholas in 2000, they had no clue that both carried the rare recessive gene that causes tyrosinemia.

A child can only get the disorder when both parents are carriers. Even then, the chances that the child will inherit the disease is one in four.The chances are 50-50 that a child will become a carrier, but not have the disease.

On the other hand, one of four children of parents who are both carriers won't inherit the gene at all. Jessica doesn't have tyrosinemia. She could be a carrier. The Harts don't know whether she is.

In April 2001, the Harts noticed something was very wrong with their baby boy. Usually boisterous and full of life, Nicholas was listless and pale. He was lethargic and vomiting, and his diapers were suspiciously clean.

"He wasn't Nicholas," Steve says. "He was just sitting there like a little bump."

Steve and Geriann panicked. They took Nicholas to Hasbro Children's Hospital, where doctors diagnosed dehydration and sent him home. Bring him back in a few weeks, they said.

The Harts weren't satisfied. Back home in Narragansett, Steve called Children's Hospital in Boston. Doctors there were willing to see Nicholas right away.

By 2 that afternoon, Nicholas was on an examining table in Boston.

For four days, doctors poked and prodded him. They ran every test they could think of and found nothing. Then a doctor suggested the problem might be in Nicholas's liver. The test for succinylacetone, the toxin found only in children with tyrosinemia, came back positive.

Nicholas was diagnosed with tyrosinemia type 1, the first case ever at Boston Children's Hospital. Not yet 10 months old, he was in danger of liver failure.

AMINO ACIDS, the building blocks of proteins, are strung together like beads on a string; each combination is a different protein. The body needs all 20. It uses enzymes to break down proteins and restrings them into substances it needs.

A person with tyrosinemia lacks fumarylacetoacetate, the enzyme necessary to break down the amino acids tyrosine and phenylalanine. Nicholas's body turns tyrosine and phenylalanine to succinylacetone, a poison that builds up in the liver and causes cirrhosis, cancer and, eventually, death.

Nicholas takes Orfadin, a medicine that provides tyrosine in its broken-down form. He eats a special diet that minimizes the amount of undigested tyrosine in his body.

Until Orfadin was introduced in the United States as an experimental drug in 1992, the only treatment for tyrosinemia was a low-protein diet and, eventually, a liver transplant. But a patient often needed more than one new liver in his lifetime. For babies diagnosed at birth, the outlook was bleak: most newborns do not survive transplant surgery.

When Nicholas was diagnosed with tyrosinemia, his doctors supplied him with Orfadin, which at the time had to be imported from Sweden. Last year the Food and Drug Administration approved Orfadin for use in this country; the medicine is now being distributed from Nashville.

NICHOLAS LOOKS and acts like a typical 3-year-old. He guides his toy train along the wooden tracks in his bedroom. He horses around with his dad. He sings along with the radio. Doctors say he can lead a normal life as long as he takes his medicine and stays on his diet.

"He's unbelievable," Steve says. "To look at him, he's a normal child. You wouldn't know. But there's a lot behind the scenes that my wife and I have to do to keep him as he is."

Steve and Geriann keep Nicholas's menus in an inch-thick white binder on top of the refrigerator; they add a new page whenever he tries a new food. Everything Nicholas eats must be weighed and the amounts of tyrosine and phenylalanine in each dish carefully recorded.

The Harts have charts made for people with other metabolic disorders that list the amount of some amino acids in foods. But tyrosinemia is so rare that the Harts must recalculate the numbers to estimate the amount of tyrosine and phenylalanine in Nicholas's food.

Nicholas's intake of tyrosine and phenylalanine must be close to 725 milligrams a day. If he has more, toxins will build up in his liver. Less, and he won't have enough protein for energy or growth. As Nicholas gets older, his doctors could lower his daily amino acid intake to prevent toxins from collecting in his liver.

A half cup of steamed fresh corn totals 350 milligrams of tyrosine and phenylalanine; a small bowl of peas totals 270 milligrams. If Nicholas doesn't eat exactly what's on his planned menu, he must compensate by eating tyrosine and phenylalanine in other foods.

To manage Nicholas's diet, the Harts order bread, pasta, chocolate, cheese, and other foods extremely low in tyrosine and phenylalanine, from a supplier in Massachusetts that makes low-protein food for people with metabolic disorders.

Nicholas is hooked on grilled cheese sandwiches made with special cheese ($10 for 16 slices) and macaroni and cheese ($30 for a 6-ounce bag). He likes energy bars ($36 for a bag of 24) and, of course, chocolate ($28 for a box of 5 bars).

Everywhere he goes, Nicholas takes a purple cooler. He knows he must eat everything in the cooler. Nothing else.

A DAY AT the Harts begins at 7:30 a.m., when Geriann leaves for the elementary school in Johnston where she teaches. Steve puts four sweet potatoes in the oven; each one has a total of about 200 milligrams of tyrosine and phenylalanine.

One of the sweet potatoes will be Nicholas's lunch.

At 9, Jessica leaves for kindergarten. Steve, a Johnston firefighter, isn't working today, so he and Nicholas are alone until the bus brings Jessica home at 4.

The cabinets above the dishwasher are stacked with Nicholas's food. Steve grabs a plastic tumbler and sets it on the scale that lives next to the calculator on the counter.

He measures 55 grams of powdered formula ($100 for each 11-ounce can, which is covered by a grant through Hasbro Children's Hospital). He adds 12 ounces of 1-percent milk. He seals the tumbler and begins to shake it. Nicholas runs over to help.

Steve pours the milky liquid into a blue sippy cup for Nicholas. Steve doesn't like giving his 3-year-old a sippy cup when he's old enough to drink from a regular cup, but it's the only way to ensure that Nicholas doesn't spill any.

Nicholas knows the routine. He reaches for the sippy cup even before the top is attached.

Twice a day, Nicholas takes 15 milligrams of Orfadin in applesauce, which has no tyrosine or phenylalanine. The monthly bill of nearly $10,000 is covered by Blue Cross & Blue Shield of Rhode Island.

But Blue Cross won't pay the $400 a month for the low-protein food. Blue Cross in Massachusetts pays up to $2,500 a year for medical-related food. The Harts have appealed three times, asking Blue Cross here to do the same.

The company has refused.

The Harts have been raising money to provide more special foods for Nicholas. They established the Nicholas Hart Tyrosinemia Fund at Citizens Bank where all branches accept contributions. They took in more than $10,000 at a dinner in September, and more money is trickling into an account in Nicholas's name.

THIRTY DOLLARS of the food budget goes for a 6-pound tub of low-protein flour that Steve uses to make Nicholas's pancakes. With syrup, Steve says, Nicholas's pancakes made with low-protein flour don't taste much different from pancakes made from standard flour.

Around 9:30, Steve makes six silver-dollar pancakes. He stacks three on a plate. He lifts each one to smear on a little butter before dousing the stack in syrup and cutting it into bite-sized pieces.

The amount of butter is small, but it's not insignificant to a child with tyrosinemia. A tablespoon of butter has 12 milligrams of tyrosine and phenylalanine. Steve records it on Nicholas's menu for the day.

Nicholas cleans his plate.

"I want more pancakes," he says.

Steve stops readying the steamer for the broccoli Nicholas will have later. He shoots a stern look at his son.

"Please, may I have more pancakes," Nicholas says with a grin.

Steve stacks the other three pancakes on the sticky plate. He butters them, douses them and cuts them for Nicholas.

While Nicholas eats, Steve figures out the menu for the rest of the day. By the time breakfast is over, it's 10:20.

ALL OF NICHOLAS'S children will at least carry the tyrosinemia gene, though some could have the disorder if his partner has tyrosinemia or is a carrier. His grandchildren could be free of the defective gene.

Gene therapy is the great hope for a tyrosinemia cure. Gene therapy replaces defective genes with healthy ones to cure genetic disorders, cancers and other diseases. But gene therapy trials have all but stopped because some patients have gotten sicker or died. President Bush has halted research on stem cells, the only known way to develop gene therapy.

"People keep saying '10 years, 10 years,' but we've been saying that for a while," says Dr. Deborah Marsden, who treats Nicholas in Boston.

Nicholas will probably see a cure in his lifetime, Marsden says. But until then, he'll make regular treks to the metabolic clinic at Children's Hospital -- once a year for a liver scan, and four more times for checkups.

NICHOLAS HAS BEEN to Children's Hospital more than a dozen times. Today he leads his father and grandmother into the elevator and reaches for the button for 10.

Before the doors have opened completely, Nicholas bounds out of the elevator and around the bend. He doesn't stop until he's squarely in the driver's seat of the red and yellow Little Tykes coupe parked by the window. He scoots through the chairs and people in the waiting room of the clinic, pretending they're houses, tunnels and gas stations.

"Nicholas Hart?" an aide calls. Nicholas carefully reparks his coupe.

They head down the hall to the weighing room. Nicholas measures 3 feet, 4 inches, putting him in the 90th percentile for boys his age. He weighs in at 44 pounds, which is off the charts. He's grown since last time.

Nicholas plays with a blood pressure cuff. He wraps it around his right calf and pumps the needle as high as it will go. 160. 180. 200. He unscrews the valve and lets the pressure out. He grins.

"You're the cutest," the nurse practitioner, Renee Charbonneau, tells him.

As they wait for the nutritionist and the doctor, Nicholas stops pumping the rubber bulb just long enough for Steve to reach into the purple cooler for Nicholas's lunch: a small bowl of steamed baby carrots (56 milligrams of tyrosine and phenylalanine), seasoned with salt and pepper.

The nutritionist, Ann W. Munier, inventories Nicholas's food log and makes sure he's been drinking his formula. Some children with tyrosinemia, especially those who were diagnosed after they had tried real milk, despise the formula. But Nicholas is eager to drink more -- perhaps, as Munier says, because he knows he'll lose his energy without it.

Marsden massages Nicholas's belly. She checks for abnormalities in his liver. He's doing great, she says. She sends Nicholas to the blood lab on his way home. She needs a blood sample to test his enzymes.

After three hours at the hospital, Nicholas has collected plenty of hugs and kisses and high-fives. He leaves Children's Hospital proudly showing off his Pooh and Tigger sticker and eager to remove the small round bandage on his arm.

He's still smiling as he leads his father and grandmother to the car. He falls asleep in his car seat before they leave the parking garage.

HALLOWEEN HAS JUST passed and Thanksgiving is right around the corner. This can be the hardest time of the year for Nicholas.

Most of the neighbors know they have to be careful when Nicholas goes trick-or-treating. Jellybeans, lollipops and gum drops don't have any tyrosine or phenylalanine, but chocolate has too much. Steve and Geriann went through Nicholas's stash and removed the candy their son can't eat.

And when the family gathers for a Thanksgiving feast, Nicholas will eat just squash and mashed potatoes. Even on special occasions, Nicholas can't have more than 725 milligrams of tyrosine and phenylalanine.

Barring a cure for tyrosinemia, Nicholas will always have those words on the tip of his tongue.

He'll have to take his own lunch to school. His sandwiches will look like everyone else's, but he won't be able to share or even taste from his friends' lunch boxes. He'll never be able to order cafeteria fare from the lunch lady.

Nicholas will always be different. But, as he grows up, he'll still be able to dream like other kids. He can be a teacher like mom, or a firefighter like dad and grandpa.