The Norman Burkholder family lives about a 2 hour drive northeast of Lancaster, Pennsylvania. The Burkholders are an Old Order Mennonite family with eight children. Their daughters, Kathryn and Ellamae were born with MSUD. Kathryn was born in 1988 and Ellamae in 1992. Mabel, their mother, heard that some of the children with MSUD had bad teeth. Their local preventive care doctor suggested giving supplements of vitamin A to maintain healthy teeth and improve Kathryn's immunity.
Over the next several years, Mabel gave Kathryn vitamin A in doses she assumed were safe. However, vitamin A in excess is toxic. When Kathryn was around 5 or 6, she had toxoplasmosis twice which seemed to have caused her spleen to enlarge. Her liver was also enlarged at times. Her metabolic doctor, Dr. Holmes Morton, was concerned and ran various tests.
Tests showed a low level of vitamin A in her blood, so vitamin A toxicity was not identified until early in 1996 when Kathryn was hospitalized for five days. She was in the end stage of liver failure. The family now faced the issue of a liver transplant. Before the family made a decision, the doctor learned that the low blood levels of vitamin A were masking a vitamin A toxicity. Knowing the cause, they hoped that the liver could recover from the toxicity.
I had hoped to have a medical account of Kathryn's liver failure and transplant to print with this article, but it was not available. However, the transplant will be covered at the upcoming Symposium '98. Phone conversations with Mabel provided some of the preceding information.
On January 2, 1997 we were on our way to the Clinic for Special Children for a check up with Dr. Morton when Kathryn vomited blood. We didn't recognize the brown "coffee grounds" as old blood, but our driver did. Dr. Morton checked her leucine levels and then sent us to the Lancaster General Hospital. Our daughter Kathryn was in acute liver failure. Dr. Morton fought for her life for several days.
She was bleeding from a ruptured vein in her esophagus. They gave medication to quickly rid her intestines of blood because the blood was being digested. According to Dr. Morton, the leucine content of the blood was about equal to the amount of leucine ingested when eating 3/4 of a hamburger, which caused her leucine levels to reach 24 mg/dl. She was dizzy, groggy-like, with her eyes only half open the first day or two. To stop the bleeding that first night, they put ice water in Kathryn's stomach through an NG tube and drew it out again to help clot the blood. It didn't work. So they took her to surgery and cauterized the ruptured vein in her esophagus. The anesthesia made her groggy longer than normal. The anesthesia along with her high leucine level made it hard for her failing liver to work off all the toxins.
She wasn't allowed to have any "free" water by mouth that first night or the following day for fear it would encourage brain swelling. She was given lots of saline in her IV which made her beg for water. Dr. Morton thought he might lose her that night.
The second day, she still did not seem like herself. I thought her actions indicated brain damage, and I decided then we'll let her go and not do a transplant. That evening when Dr. Morton came in, he told me I couldn't judge by what I was observing. Her poor responses were due to the toxins still in her system. It was taking longer to work off the toxins because of her failing liver. Her leucine was no longer elevated and was not affecting her. So the whole turmoil of indecision about a liver transplant started up again!
The half year before this episode - after discovering her liver failure - Dr. Morton was trying to balance the amino acids to keep her MSUD under control. He did not give a bit more than necessary, so her liver wouldn't have to work with an excess of amino acids. Two companies supplied individual amino acids which Dr. Morton used to make a formula. He used Farm Rich, a non-dairy creamer, and the mix of amino acids he thought best. He tried to eliminate all Vitamin A from her diet in order to reverse the liver damage.
After this big bleed, Dr. Morton was afraid Kathryn might not make it much longer. He wanted us to decide whether we're going to do a liver transplant. When we went home that night, I explained the situation to the family. There is no chance of life as she is now, and she would have a 65% chance with a liver transplant. We asked our children what they think we should do. Melinda said, "Oh, give her a chance." And Edwin, the one who often fought with Kathryn, said, "Yes, do the surgery!"
Well, we felt lost, and you always think doctors may be making it sound worse than it is. We didn't decide right away, and then she "leveled out" a bit - stabilized. The third day, she actually understood her schoolwork again.
After we were convinced the doctors were right about her chances, we said okay to the transplant. But by the time we'd made a decision, she was so much better and no longer an intensive care patient. She wasn't eligible for the number one category anymore. If we had made our decision the first night, she might have had a new liver in 24 hours, Dr. Morton told us.
With the decision to do surgery, I prayed that God would take her before the surgery if the new liver was not going to be a good match, or if we should not do the transplant at all. The way Dr. Morton talked it seemed her life was very much "on the edge."
We realized later if we would have decided to let her die, her stay in the hospital might have been even longer. She couldn't eat because of the pancreatitis and Dr. Morton didn't think she would have been able to eat again.
We are also glad we didn't have to do the transplant then. We have heard since of other persons who were given a mismatched liver when it was a life-and-death matter and later needed another transplant.
During the month and a half that Kathryn was in the hospital before the transplant, she developed pancreatitis, so she had to stay on an IV the whole time. The back pressure caused by the blocked liver created pressure on her pancreas and lungs.
Kathryn had low oxygen saturation for a year or so before this episode. Pressure built up from the blood not being able to go through her liver freely and created shuntings in the lungs. The blood actually bypassed some of the oxygen-making places in the lungs, going through the little shuntings created by the extra pressure. That same pressure caused varicosities (varicose veins) the thickness of an index finger all the way down her esophagus into her stomach. Dr. Morton had been afraid of having those veins rupture during the half year that we tried to reverse the toxicity of the liver but I'd forgotten he said that.
She was coughing so much the last week before her big bleed, coughing hard every time she drank her formula. She wanted it quite warm and asked for "quick water" (water quickly) after her formula to keep her cough from making her throw up. We realized later anything cold probably aggravated those big veins in her throat dreadfully. But since I'd forgotten about the possibility of varicose veins, I didn't tell the doctor about this reaction right away.
Being on IV's for a month made her liver worse, so her pancreas didn't get better either. Her eyes got very yellow in the corners. Some days she was better and we almost had hopes of bringing her home.
I'm glad now that I didn't know that Dr. Morton believed she would never be able to eat food again without having a new liver. Knowing this, and that being on the number two list for a liver transplant meant it could take half a year before a liver was available, would have been quite depressing. I believed she would get better and could go home.
The third week in January she was taken to Philadelphia by ambulance (without sirens) to have an evaluation. After one week at Philadelphia, she was back at the Lancaster Hospital which felt like home by now.
During this time Kathryn was on IVs which advanced the liver failure, and Dr. Morton kept fearing another bleed. This would cause very serious problems with her MSUD. He tried to get the officials from the transplant center to hasten the transplant. The officials finally said they would discuss metabolic patients getting priority status at their next meeting.
Before two weeks were up, Kathryn had another bleed. It was not as scary or as big a bleed as the first time, but, by needing intensive care, it put her back on the number one list for eligibility. So we rushed Kathryn to Philly, sirens going this time, and admitted her to ICU in the Children's Hospital of Philadelphia (CHOP). To me it was "just a comfortable little bleed," even though she did pass out from toxins, etc.
As we entered CHOP, I was scared to be without Dr. Morton for fear Philly doctors would miss something with her complicated case. After being there almost a week, they found a good liver. The first liver they'd prepared for her was turned down by Dr. Shaked, which increased my faith in him. He knew that many doctors, nurses, etc. had been working towards a transplant, and yet he was able to refuse the liver because it had abnormal routings, and Kathryn was stable enough at the time. He could've used it if she'd been too sick. However, the extra rerouting of tubes to connect that liver's abnormal routings to Kathryn's could have caused more chance of rejection. We've been relieved often thinking about it. She barely had any rejection with the liver they found for her three days later.
The week before her transplant, while Kathryn was in the ICU, she got so much better that Dr. Morton was afraid she'd be taken out of ICU and put on the regular floor. That would put her on number two status again. Then he would've had to struggle to get her through the next big bleed. We believe God saw to it that there were little problems that week in ICU - enough to keep her in the ICU and on the number one list for a liver. Kathryn's insulin and glucose levels fluctuated, and another bleed one night caused her leucine levels to elevate to 14 mg/dl again. When I got uneasy about something, I'd call Dr. Morton.
Kathryn's liver came from a small 22 year-old woman on Feb. 12. They had prepared to give an adult in an adjoining hospital the right lobe of the liver and Kathryn the left (smaller lobe). However, the liver was small enough to fit the complete liver into the cavity from which Kathryn's failed liver was taken.
Before the hallelujah of coming home, we had many ups and downs in the ICU and later on the seventh floor. For five whole weeks we experienced both anxiety and hope after surgery. Reading back over the diary I kept, it now looks like this was the biggest cliff we plunged off yet.
When we had questioned Dr. Morton about the shuntings and the low saturation problem, he said it would reverse itself immediately after the liver transplant. But Kathryn's oxygen saturation remained low after the transplant. Dr. Morton's explanation made sense to me - when they used hyperalimentation (TPN by IV) after the surgery, the new liver was filled, making it larger which caused slight pressure on her lungs, enough to keep the shuntings in her lungs open.
His theory proved correct. When IV intake was decreased in preparation for going home, her oxygen saturation jumped from 60 to 80%. In a week and a half after being released from the hospital, they tested 99%. Relief! We thought that problem would vanish immediately after surgery, but it took a month! Now no more purple lips and fingernails and a normal flesh-colored face for Kathryn, just like other children! No more getting short of breath from walking or playing.
Kathryn was discharged from the hospital on March 21. After Kathryn was at home, she started eating better. She'd been unable to eat for one and one-half months before the surgery - maybe that's why it took awhile for her appetite to return. Or maybe because of so many medicines. Anyway, she'd started eating ham roll and other meats quite heartily about one month before her two months of tummy aches started.
After she started having tummy aches, Dr. Morton thought it might be an ulcer, so we tried to get scheduled for an endoscopy. I guess other parents would've said, "Here we come, she needs to be hospitalized." But we struggled to feed her for four weeks until she finally got scheduled for an appointment.
By that time, I was afraid she was dehydrating from throwing up several times a day. She would lie on the sofa with tummy ache for hours at a time, sometimes throwing up tiny clots of blood. I was afraid her stomach would rupture and hemorrhage if we let it go one more weekend! Finally they checked her at CHOP and kept her.
The doctors diagnosed an ulcer with lymphoma around the ulcer - a drug-induced lymphoma they said. So she was given acyclovir by IV. In Philadelphia, they said if they can't heal the lymphoma by withholding the Prograf, they would use chemotherapy. (Prograf is an immunosuppressant drug to prevent the body from rejecting the liver.)
In the meantime, I was in contact with friends who had been treated in a hospital in Pittsburgh. The doctors in Pittsburgh were much more experienced with lymphoma. Philadelphia had 18 cases, but Pittsburgh had probably a hundred or more. Pittsburgh treated all their cases without chemotherapy.
We were at CHOP for 2 , weeks (Aug. 12 to 28, 1997) and at home with an oral acyclovir for the lymphoma for 1, weeks. To heal the lymphoma, they had to withhold the Prograf for as long as the liver didn't show signs of rejection. When Kathryn was released from CHOP, she tested positive for the Epstein-Barr virus, so they changed the oral acyclovir dosage to a therapeutic level every 8 hours plus one dose at nighttime. Kathryn went to the first week of school with some tummy aches.
Dr. Reyes from Pittsburgh said their research shows that oral acyclovir is worth almost nothing in treating the Epstein-Barr virus. It seemed to prove him right when by the end of the week at home, Kathryn's tummy aches made her cry once or twice a day again. By then we had scheduled a trip to Pittsburgh to give her a thorough check up and get a second opinion.
Well, the second opinion turned into another 2 , weeks stay at the Pittsburgh hospital (Sept. 8 to 25, 1997). But she was the healthiest child on the floor and to her it was a "joy ride." We felt like the luckiest parents on the floor. We also came to realize that no matter what hospital you are in, Epstein-Barr virus and lymphoma in a transplant patient are very hard to treat correctly.
One boy at Pittsburgh had the same lymphoma as Kathryn. He had been treated in Boston first with chemotherapy which actually made the lumps grow. We felt heaps of relief that we went to Pittsburgh before Kathryn was given chemotherapy. I sincerely thank the three hospital staffs for doing all they could for Kathryn and us.
Two days after Kathryn was admitted to the Pittsburgh Children's Hospital, they replaced the oral ayclovir with IV gancyclovir. On her fourth day there, they put a scope down into her stomach and discovered CMV, a virus that isn't touched by acyclovir. Can you imagine the relief we felt that it was discovered! We were very glad we had sought a second opinion. Now we were confident that putting her in the hospital, even though she seemed much better, was the right move.
We had been afraid the doctors would miss just one little thing that would make all the difference. Pittsburgh had a great deal of experience with liver transplant follow-up and we liked the way they treated aggressively.
We also heard of a child that was given only one lobe of liver and later got leakage of either blood or bile causing infection in the intestinal cavity. That makes us glad that God directed it all and Kathryn got a whole liver (which is not the usual).
Right now Kathryn's at home and very healthy. Just Friday morning, it amazed me again that she can actually jump on her bike and easily make it up the little hill past our barn. For the last few years, others had to use a wagon or cart to take her out the lane to the school bus stop. She's actually chubby now (without any Ensure or IV) and back to liking some meats. While she had tummy aches, she preferred all low protein foods - because protein is harder on a sick tummy?
She still likes MSUD formula on her cornflakes and likes Cremora "cheese" sandwiches made with rusks, or rusks buttered and browned on both sides. She prefers low-pro bread to ours (even though the last loaf I made is coarse and hard) and sometimes helps Ellamae eat her low protein noodles or soup. Tomato soup is still better her way (Cremora instead of milk). But I have to think, which one of us could change from eating our cornflakes with milk to eating them with MSUD formula! It is the same for her - it doesn't taste right with our milk.
We want to thank the many people who supported us with cards, letters, phone visits, prayers and financial support. All of these helped us get through this ordeal. Looking back, it looks almost impossible to have stood it all without completely collapsing. Our thanks to everybody, especially God.
Kathryn missed a lot of school and was so miserable before her transplant. Now she loves school and her learning is much improved. She is nine and repeating the first grade. Because of all the attention she received, she does have a problem with temper tantrums which the family is dealing with.
Kathryn enjoys her baby brother, born on October 29, 1997. He has MSUD, so the family still has two children on the MSUD diet, baby Norman Jr. and Ellamae, 5. Kathryn is gradually giving up her interest in her old diet and adjusting to being able to eat any foods. However, she still likes to eat some low protein foods made for her brother and sister and drink a little formula when she gets a chance.
Baby Norman has been a healthy baby and weighs 17 lbs. at 4, months. He was tested for MSUD within 24 hours of birth and started on the diet on the second day of life. He has had only one hospitalization - an overnight stay at the Lancaster General Hospital. At that time he had an asthma-like tightness that was treated with a nebulizer. It seemed he got tight from the slightest breeze or a cold room, but only when his leucine was too low. He gained weight so fast the first three months that his leucine level was often way too low. His mother started sending blood on filter paper to Dr. Morton by overnight Fed-Ex twice weekly at times. This helped.
Although Kathryn is doing really well, a liver transplant is not the cure-all for MSUD. It is a risky procedure and very expensive. The cost for Kathryn's family, who has no medical insurance, was over $500,000. Costly anti-rejection medicine and follow-up treatment will continue throughout Kathryn's life. After Kathryn's transplant, the local community pitched in with fund-raisers. One auction raised $27,635 for Kathryn's medical fund.
This family had many exhausting challenges in the last couple of years but through their experiences, many persons have become aware of MSUD. Medical research has been advanced. Kathryn is enjoying life. The Lord has brought blessing out of adversity.