Welcome to the Crigler-Najjar Syndrome Web Site

Prognosis

Before the introduction of phototherapy most children with Crigler-Najjar syndrome type I

either died in early infancy or developed kernicterus later in life. Phototherapy has

changed the natural history of this disease. Currently, with the proper use of phototherapy,

bilirubin levels can be controlled and prolonged survival free of neurologic deficits is

possible. However patients managed on phototherapy remain at risk of sudden

decompensation with a steep rise in bilirubin.

Without treatment the jaundice continues to increase, causing kernicterus and eventually

death. This was the fate of many of the patients initially described by Drs. Crigler and

Najjar and others. However, with modern management, the level of jaundice can be

lowered and kept under control for prolonged periods.

Management of Acute Illness

Preventing Bilirubin Encephalopathy - Management Of A 'Bilirubin Crisis'

With phototherapy most patients have well controlled bilirubin levels. However all patients

are at risk for a sudden rise in bilirubin level, which can rapidly cause encephalopathy.

Such a rapid rise can have many causes (see above). It is important for parents,

physicians and the patients themselves to recognize the risk that such episodes represent.

During such an episode the patient may have altered sensorium, inco-ordination, slurring

of speech, weakness and can eventually become comatose. Recognition and treatment of

such an episode must be quick. Serious delays have occurred in treatment because the

physicians managing the patient were either unaware that the patient had Crigler-Najjar

syndrome or were unaware of how to manage severe hyperbilirubinemia. Patients with the

Crigler-Najjar syndrome type I should consider wearing a Medicalert bracelet.

When faced with a newborn infant with hyperbilirubinemia pediatricians, family

practitioners and neonatologists, who typically are used to managing infants with relatively

benign causes of hyperbilirubinemia, may not consider the possibility that they are dealing

with the Crigler-Najjar syndrome type I and may under treat these infants. The American

Academy of Pediatrics has issued a practice parameter for the management of

hyperbilirubinemia in full term infants (Pedatrics 1994; 94: 558-565). However , it is

important to remember that these guidelines apply to healthy full term infants with

hyperbilirubinemia and do not apply to patients with Crigler-Najjar syndrome type I.

There are several options for emergency management of severe hyperbilirubinemia:

1. Intense phototherapy should be started.

2. Exchange transfusion. A double volume exchange transfusion is useful in the

management of neonates with severe hyperbilirubinemia.

3. Plasmapheresis has been successful in dramatically reducing high bilirubin levels in

patients with the Crigler-Najjar syndrome type I. Plasmapheresis may have to be repeated

several times.

4. Tin mesoporhpyrin can be an useful adjunct to the acute management of patients in a

bilirubin crisis.

5. Liver transplantation on a relatively urgent basis should be considered if there is no

response to the above measures.

Latest Conference Abstracts

From the Rotterdam Conference, April 29th, 2000 presented by Dr. Maarten Sinaasappel-

Neuropsychological development

Hans M. Koot, Ph.D., Erasmus University Rotterdam, Department of Child and Adolescent

Psychiatry, P.O. Box 2060, 3000 CB Rotterdam, Email: [e-mail]

The Crigler Najjar (CN) syndrome is associated with a number of neurological sequelae

that tend to evolve abruptly and episodically rather than by slow progression. As yet no

clear associations with type of the genetic defect, unconjugated bilirubin levels, medication

or neurophysiology have been found. Unfortunately the neurological sequelae have not

been documented systematically using similar assessments in a sizeable group of patients

in association with these factors. Furthermore, the effect of this disease and its treatment

on the quality of life of the patients and their families has not been a subject of

investigation. The care for a sizeable group of patients with CN in our hospital provides the

opportunity to address both of these issues. Therefore, the aim of our study is to answer

the following questions:

1. How is the neurological and neuropsychological function of Dutch CN patients in relation

to the type of the defect (Type I or II), their (free) bilirubin levels, medication, and

neurophysiology?

2. Is it possible to detect the risk of neurological damage in an early stage of the disease?

3. What are the effects of having the Crigler Najjar syndrome on the quality of life of

patients and their families?

All patients with Crigler Najjar who are older than 4 years and are treated in the Sophia

Children’s Hospital and the University Hospital Rotterdam - Dijkzigt (n = 17) will be

enrolled in the study. Patients will complete neuropsychological tests, and patients

themselves and their parents or partners will complete questionnaires concerning quality

of life of both patients and their families. For all patients extensive standardized and

clinical information is available. Patient outcomes will be compared to normative data and

neuropsychological outcomes will be related to medical parameters including type of the

defect (type I or II), (free) bilirubin levels, medication, and neurophysiology using

appropriate parametric and nonparametric measures of association.

Shevell, M.I., Mejnemer, A., & Schiff, D. (1998). Neurologic perspectives of Crigler-Najjar

syndrome type I. Journal of Child Neurology, 13, 265-269.

"This section contains stories and experiences of actual patients with

Crigler-Najjar syndrome. We invite other families to submit their own

stories to us by email or regular mail, so that we can put them up on

this site. To protect your confidentiality, please use first names only

or just initials and do not use any identifying characteristics. Pictures

of persons with Crigler-Najjar syndrome are also welcome."

Gautham Suresh

2002 Pictures- New!

Amy and Derick with their new colt, Paint.

In June, 2002, three CNS families recently visited Woodward Cave in PA.

From left to right: Katherine (non-CNS), Joyce, Dawn, Eric, Amy & Derick

in front: Matthew (non-CNS) and Thomas

Waiting for a cure

Gene therapy a hope for beating disease

By Patti Levine-Brown River City News correspondent

The Florida Times-Union

Wednesday, January 3, 2001

Two-year-old Melanie Bryant has to sleep under intense blue lights

to help combat the disease Crigler-Najjar Syndrome.

- John Pemberton/staff

Research in the field of gene therapy may be the answer to a prayer for two Jacksonville-area kids who

suffer from a rare and deadly inherited liver and metabolic disease.

Melanie Bryant, 2, and Ric DeVere, 16, have a condition known as Crigler-Najjar Syndrome.

Melanie and Ric take numerous medications and sleep under special blue lights. This process, called

phototherapy, helps break down bilirubin, which can become toxic to the brain if levels get too high,

causing damage much like a stroke.

In those with Crigler's, the bilirubin cannot be excreted from the body, which causes jaundice -- a

yellowing of the skin and whites of the eyes.

"Kids have always come up to me and asked why my skin looks yellow," Ric said. "I remember when I

was in the third grade I told them I was an alien. I do get aggravated sometimes if someone makes fun of

me, but I spend most of my time concentrating on staying healthy and hoping for a cure."

Crigler's does not always strike every child in the family. Melanie's twin brother, Michael, and Ric's

younger brother, Hunter, do not have the disease.

Studying families with children who had the disease in the 1940s, physicians John Crigler and Victor

Najjar found that parents could be healthy carriers of a recessive gene that causes the disease, and that

their children would have a one-in-four chance of inheriting the syndrome.

Steve Bryant carries his daughter Melanie, 2 , to her specially designed bed he built with blue lights

to combat her liver disease. Said Bryant: "None of us are giving up hope on the possibility of a cure

through gene therapy, but we want it to be safe."

-- 

John Pemberton/staff

The Bryants, who live in Arlington, and the DeVeres, who recently moved from Ponte Vedra Beach to St.

Augustine, spent months doing their own research on the disease, which led them to Holmes Morton, a

Harvard-educated pediatrician trained in biochemical genetics who worked under Crigler and now runs a

special clinic for children with the disease in Strasburg, Pa.

Both Ric and Melanie were tested and shown to be good candidates for an advancement in gene therapy

known as chimeraplasty, which is intended to stimulate the patient's own cells to repair the defective

gene.

"For years it was very frustrating because we knew Ric was sick, but most doctors did not understand his

problems, and we ended up having to take over our son's medical care," said Katie DeVere, Ric's mother.

"It was hard to find answers about how to manage his condition because so few doctors knew how to

treat this syndrome. Dr. Morton has spent many hours guiding us on what to do for Ric. We think the

world of him."

Today, the teenager still suffers from chronic fatigue that often keeps him bedridden, but his mother says

it is not as bad as it used to be.

"The fatigue has just about taken away everything Ric used to enjoy doing, including being in school with

his friends," Katie DeVere said. "He now has a homebound teacher who is wonderful, but he misses his

friends who want him to be able to go along with them. We are proud of how Ric handles his condition,

but we all wish he could do the same things others do."

His teacher, Sandy Becker, says Ric is a typical teen who happens to have an ailment that keeps him

from doing things he would like to do. "He is a terrific student with a lot of insight," Becker said. "His

biggest frustration is that he wants to go to school, but he has limited energy that goes in cycles. It seems

that every time I read an article on gene therapy, there has been some new development. I know it is

bound to come, but I also know that Ric would love for them to hurry."

Ric, now a 10th-grade homebound student at Nease High School, can only make it to the campus

occasionally, but school officials have been understanding. The Bryants say Ric serves as a good role

model for Melanie and other kids with the disease who will need his kind of courage and determination to

get through their ordeal.

Melanie's parents, Debra and Steve, say they are grateful her condition is presently under control. If gene

therapy does not work, children may require liver transplants.

"We have been encouraged by the efforts of doctors who are trying to improve the quality of gene

therapy," said Steve Bryant. "None of us are giving up hope on the possibility of a cure through gene

therapy, but we want it to be safe."

Both sets of parents realize that medical costs could become catastrophic, especially if a liver transplant

is inevitable.

"The children with this disease go through a lot, and we think all of them are heroes," Debra said.

"Melanie is taking several pills a day, and these medications are expensive." Ric takes 10 pills four times

a day. His monthly medications run in excess of $500. Still, he continues to have a positive outlook.

"I believe Dr. Morton saved my life, and I want to do the gene therapy," Ric said. "I do not want to have a

liver transplant because it doesn't always work, and I don't want to have to take anti-rejection medication

for the rest of my life. I get very sad when I think of the boy in England who had a transplant and then got

cancer from the anti-rejection medicine." "This is a race against time for Ric, and everyone is doing all

they can to keep him healthy," Katie DeVere said. "Our children are the best, and we wouldn't change

them in anyway, except to cure them, so we continue to pray for a cure in the new pioneering gene

therapy."

Morton has high hopes for success. "If gene therapy works, it will change my life as much as the children

it will help," he said. "As a physician, I know we are running a race to keep these children healthy, and my

job is to keep them healthy until we can treat the disease. If gene repair works, it will completely change

our approach and understanding of how we treat genetic diseases."

Reprinted by permission. 01/20/01

Hello! We are thankful that you are taking the time to learn about Crigler-Najjar Syndrome and some very

special children. There are a few Crigler Children in my family. Two are my own.

Derick was born on February 5, 1990. A picture of health, or so we thought! At five days old, he was very

jaundiced. His bilirubin level was 22 mg/dl (380 umol). The normal value is 0-1 mg/ld (5-10 umol). He was

admitted to the hospital and phototherapy was started. After the fifth day in the hospital, his level was 16.

Finally he was able to come home. We had access to a bilirubin light at home and we had to keep him

under it 24 hours a day without a diaper. What a mess! Until he was five weeks old, the level never went

below 15. It was a very difficult time for us. I cried buckets! Finally, the doctors concluded that he had

Crigler-Najjar Syndrome Type 1. We were devastated! We thought that he would never walk or go to

school because 8 years prior, a nephew on my husband’s side had Crigler that caused severe

neurological damage. He died at age three.

God hear our prayers! When Derick was 6 months old, we found Dr. Holmes Morton. Dr. Morton had

gone to school with Dr. John Crigler, founder of Crigler-Najjar Syndrome. He has helped us in so many

ways and to understand what Crigler-Najjar Syndrome is and how it works seemed so amazing to us.

Our beautiful daughter Amy was born two years later, April 25, 1992. She also has Crigler-Najjar

Syndrome type 1. It wasn’t easy accepting it the second time around. We got very little sleep. Amy hates

her lights. None of the other families we knew about had two children with Crigler. Now we see the

benefits of having two children with Crigler-Najjar. They are a team. They have each other to talk to and

they stick up for each other when mom makes them take medicine. When children ask Derick why he is

yellow, he says, "I have Crigler-Najjar Syndrome and I sleep under a blue light. My sister has it too."

When Amy was 2-1/2 years old her bilirubin went up to 39 (670). She had the flu and an ear infection. We

kept her under the bili lights 24 hours a day. We ate, played, and slept under the light. She is a miracle!

Another boy we know died after a bilirubin of 39.

For years, both Derick and Amy suffered from unexplained stomach pain. Then at age 6 and 4, Dr.

Morton discovered that half his Crigler patients had gallstones. Both children had laproscopic surgery.

They recovered just in time to travel to NYC to attend the first Crigler-Najjar conference at Rockefeller

University.

After Amy’s surgery, she still complained of bellyache, chest pains and ate poorly. She was then started

on Actigal. What a big difference it made! We will never forget the time I only bought one ice cream cone

for both of us because she only ever had 2 licks and I always got the rest. Well, this time she ate the

whole cone and I only got 2 licks! We were so thrilled because she was finally happy. The Actigal also

reduced their bili levels by 30%.

Derick was having a lot of problems with fatigue. He would lag on behind when biking with his friends. In

the evening he would be so tired that he would sit on the steps crying because he could not go up to bed.

Wee had to carry him to bed until I got pain in my back because he was too heavy. When he would wake

up in the morning, he would still be tired. We finally took him for a muscle test at Philadelphia Hospital. He

now takes creatine 4 times a day and says he feels much better. He can now keep up with his friends and

can run up and down the stairs again. Thank God.

My husband makes the bili lights and has sent them all over the U.S. as it is difficult to find lights for these

older children. We keep in touch with Crigler families all over the world: Australia, England, Germany,

Holland, Italy, Canada, New Mexico, and 8 different states.

We are all looking forward to chimeraplasty. The children already have their pjs and blankets picked out

for the first night without lights.

Derick and Amy’s story and photos have been in several newspapers and magazines including The New

York Times, The Daily Item, National Geographic, Philadelphia Magazine, and Fortune.

April 13, 1999 we were blessed with a baby girl! Katherine Joy. She does not have Crigler-Najjar and isn’t

even a carrier! We praise the Lord every day!

To all the new Crigler parents, do not give up! God made these children special. They are all beautiful

and have a lot of spirit and fight. The future looks bright for them.

Love and prayers,

Katie

Hello from Mifflinburg, PA

Dawn was born on March 16, 1995, on her grandmother’s birthday. She was all that we could have

wished for; we felt totally blessed!

We noticed that she was getting more and more jaundiced, even though we were keeping her in the sun.

At six days old, we got a bilirubin level done through our pediatrician. Her level was 20, so she was

admitted to the hospital for phototherapy for 24 hours. Our hearts were broken to see our precious baby

girl with no clothes on lying under that awful bright light. That night we prayed that God would make the

yellow go away. Memories flashed back of caring for my brain damaged nephew who died at age three

from Crigler-Najjar Syndrome. During that time, I was between ten and twelve years old. I remember how

I felt when he died. I thought some day I would like a baby like Kevin. He was so sweet, and he was the

joy of my life. But all that changes as the years go by, and now my own daughter was under lights!

By her seventh day of life, Dawn’s level was coming down, but only going back up. So, we had a light

made, and tried to accept the fact that she has CNS.

Two and a half years went by and a little boy, Eric, joined the family on October 3, 1997. At this time, the

gene test was available, but due to a two week delay, we put him under the lights. Doctor Morton called to

tell us what we thought we already knew. He had CNS. He was a content baby and did not mind the light

or the sun, so this made it easy for me.

By the age of three, Dawn was quite independent and feisty. She would wake up and lie on the sofa

during the night. If I tried to carry her back, she would scream, so I waited until she fell asleep to turn on

her light. Nighttime was a busy time. I could tell if they did not get their 8-10 hours under the light. During

this time we did not have the Urso which helps to keep their levels down.

Joyce was born on March 25, 1999. She was a chubby, round faced little one that had more or less the

nature of our first one. We got our test result five days after she was born. She was already yellow at

three days old. We did not want to see it; we were living in denial, yet in our hearts was a great fear we

could not push aside. It was an emotional roller coaster. We thought no one ever had three CNS children

in a row, so why should we?

I do not have the words to describe the feeling or the days there after what we had to go through, but we

believe in a great God and he makes no mistakes. We had to believe that Joyce was no mistake. Looking

back, we would not give up any of our children to have an easier life

We look forward to the day they may not have to sleep under the lights, so they too, can lead normal,

healthy lives. We are more fortunate that we have always known people with CNS children. I am thankful

for the support we have from all of the parents of Crigler children, and last but not least, from Doctor

Morton.

Best wishes,

The Martin Family John, Miriam, Dawn, Eric, and Joyce

08/22/00

Fourteen families with a child/children with Crigler-Najjar attended a barbeque at the home of John and

Meriam Martin in Mifflinburg, PA on July 22nd. Most of the families live in Pennsylvania, but others

traveled from Ohio, Wisconsin, and Kentucky to attend the gathering.

The barbeque provided the parents a chance to talk and share experiences about the disease, and it

allowed these very special children a chance to meet and to play with each other.

The Crigler-Najjar children who attended ranged in age from ten months old to sixteen years old. Dr.

Holmes Morton and his wife, Caroline, also attended

8/8/00

The Story of Thomas

Thomas was delivered by c-section on September 2, 1999, ten weeks before his due date. I knew he was

going to be a small baby, but I never imagined that he would weigh less than two pounds. He was in the

NICU for a total of sixty-eight days. He could not come out of his isolette very much because he was

jaundiced and needed phototherapy.

As Thomas got older, he gained weight and started drinking from a bottle. Still his jaundice persisted. At

about eight weeks old, he had double hernias repaired. He was barely five pounds at this point, but he

successfully pulled through.

Doctors kept telling us that they had never seen a baby with chronic jaundice. After consulting medical

texts, it was assumed that Thomas must have Crigler-Najjar.

Over three months went by before some test results came back. I searched the Internet for information on

this rare topic. I was not sure what the future would hold for a child suffering from this condition. It was not

until I was put in contact with families who have children with Crigler-Najjar that I felt hopeful. They

reassured me that the children have normal lives except that they must sleep under bililights every night.

Thomas is now crawling and doing things every baby does. He is a beautiful, happy baby. Looking back,

the prematurity was simple compared to dealing with a rare disease and living in fear of what may

happen.

I used to say "Why did this happen to my baby?" Now my view is that Thomas was one of a few who was

chosen to be included in a special group of people. I pray that gene repair will work on these children and

that gene therapy can someday cure many diseases.

I am so thankful that the families I have contacted are so willing to share their knowledge with me. One

mother I spoke with said it took her thirteen years before she found other families dealing with Crigler-

Najjar. I thank God it only took me five months.

Kathleen