Boston - September 1, 1999 - Scientists working on the Neurogenetics Unit at Massachusetts General Hospital (MGH) and the Harvard Institute of Human Genetics have discovered that defects in a gene that maps to human chromosome 19 are responsible for the disease Mucolipidosis Type IV (MLIV). The research team, led by Susan A. Slaugenhaupt, Ph.D., and James F. Gusella, Ph.D., reports its findings in the September issue of The American Journal of Human Genetics.
MLIV belongs to a group of inherited diseases known as the lysosomal storage disorders, which includes the more widely recognized diseases Tay-Sachs and Gaucher's. It is a devastating disease that causes severe neurologic and eye abnormalities in children. MLIV was first described in 1974, and the majority of patients diagnosed to date are of Ashkenazi Jewish descent.
The MGH researchers collected information from 26 MLIV families through close collaboration with the MLIV Foundation and scientists at the National Institutes of Heath and at Hadassah Hospital in Israel. These families were tested with DNA markers that map to each human chromosome, and the analysis revealed that the disease was always inherited with specific DNA markers on chromosome 19. The scientists went on to show that, in the Ashkenazi Jewish population, 98 percent of affected individuals share only 2 chromosomes.
This research has laid the framework for the eventual cloning of the MLIV gene using a technique known as positional cloning. Now that scientists know where the gene is, they can go on to pull out genes from the specific region on chromosome 19 where the markers are located and test them to see of they contain the MLIV mutation. Once the MLIV gene is cloned, carrier testing can be offered to the Jewish population, and more importantly, researchers will have in hand the key to develop an effective treatment for this devastating disorder.
GRANDPARENTS' CORNER
by Florence Yudenfriend
When asked to add some thoughts and feelings for this newsletter, I actually felt threatened. It meant confronting emotions openly with people that I don't know and who cannot understand the depth of feelings in having an ML4 grandchild - of letting people in on the pain and anger of hearing a pediatrician pedantically proclaim - "Oh Grandmother, why are you so worried? Are you a school teacher?" - this in the nastiest patronizing manner possible - (I would be glad to give the name of this "prominent" pediatrician).
When Lauren was originally diagnosed, I could barely look at another child her age without thinking "this is what should have been". With time comes a realization "this" cannot be - however the unconditional love these children deservedly demand, and are given cannot be surpassed.
Watching an ML4 child struggle to get on her knees and STAND!! - Something other children do 1-2-3 had us all cheering. Every hard fought tiny bit of progress is stored away for when there is discouragement.
Lauren, who is a beautiful teenager just celebrated her 17th birthday. Though she is at a school upstate we regularly make the trip to see her and delight at her presence and her wide smile when she hears her grandfather sing his special songs for her.
We call Jonathan "lover boy" because everyone who meets him loves him and takes him to heart. When he pulls you to hug or beckons you to sit close, you feel the depth of the love of this most innocent child - and your heart sort of melts.
I've watched the ML4 Foundation grow from a small few families where we used to meet in each others houses - making continuous, if slow progress to a foundation still having as its backbone the families, their families and their friends - to one that funds world renowned researchers who are always impressed with what these families and their friends have accomplished.
And we have accomplished. Last month, at an ML4 meeting, we heard tremendously exciting news - I kept pinching poor Mary Jo with disbelief - at the news of the discovery of the ML4 chromosome. Do you realize - can you imagine our hope and excitement over the possibility of one day seeing a treatment, and dare I say, a cure.
I hate asking my same family and friends to attend a function, buy some raffles and so forth - but I kept telling myself this is not for my children - this is for theirs. We didn't know or expect ML4 children. Because of our "foundation" all families will know-and I'm going to say it again-maybe one day see a treatment and cure.
"Maybe she'll learn to speak Spanish." Those were the words spoken to us by our son eight years ago. He was talking about his sister Rachel who was not developing the way he had or the way other children her age were. We didn't know why. We only knew that Rachel was not like other one-year old children and we wanted to find out why.
When we were first told on a Friday that Rachel had some "eye problems" that had to be addressed on the following Monday, we never knew what lied ahead for our family. Numerous trips to hospitals as well as hundreds of phone calls all over the world were pursued with the goal of finding someone who could tell us why our daughter was not like other children. Unfortunately, the answer did not come easily and was certainly not the one that we were hoping to receive.
We found the answer at first in a booklet that contained a list of Jewish genetic diseases, one of which was ML4. The description of ML4 was contained in several short paragraphs that were found on two small pages. The words describing Rachel's condition will never be forgotten: cloudy corneas, mental delay, and psycho-motor retardation. These were not the words we wanted to start using to describe our daughter Rachel. Our vocabulary, goals and life styles all were to change. Our first goal was to find someone, anyone, who had ever heard of ML4. We spoke with many doctors all over the world but did not find many who had ever heard of Rachel's condition. We wanted to find someone who was going to tell us that they were working on a cure, or at least a treatment, for ML4. Unfortunately we did not find any one who fulfilled this goal.
When Rachel reached pre-school age we were able to get her into an approved private school, The Western Pennsylvania School for Blind Children ("School"), a Pittsburgh landmark that was over 100 years old. This event dramatically changed our lives. Rachel continues to be a student at this School, seven years later. She loves her time at the School when she can be with friends and participate in the activities that she loves: swimming, art, and most of all, music. When you mention the word "school" to Rachel, you will suddenly see one of the brightest smiles that you have ever seen.
Rachel's condition is not unnoticed in the Pittsburgh community. She is a frequent attendee at all of her brother's baseball, football and basketball games. As people pass by, young, old and in between all smile and stop to say "Hi Rachel! How are you today?" Rachel is not ignored but rather is treated like other members of our community.
Probably the highlight of the support that we have received to date from the Pittsburgh community occurred in October of 1996 when we held a find raiser to support the research that was being sponsored by the ML4 Foundation. We obtained a first run movie and decorated an old neighborhood theater that had only one screen. Food and waitress service from local caterers and restaurants were donated. Numerous prizes were donated for a silent auction and a raffle. Since we had never done anything like this before we had no idea what to expect.
Our goals were modest - maybe a few of our friends would attend the fund raiser, we would raise a few dollars to support the ML4 Foundation's projects, and we would have some fun. Much to our surprise and delight, over 350 people attended our fund raiser. Although we knew most of those in attendance, they all knew about Rachel.
There were also others who supported our fund raising efforts by making a contribution even though they could not attend our gala event. When all the donations were tabulated we found that we had raised more than $25,000. None of that would have been possible without the warm support that we received from all of our friends, neighbors and families.
Every day researchers are coming up with new "miracles". We are waiting for the "miracle" that will help Rachel. We hope to have another fund-raiser later this year to help fund the research being conducted on ML4. Rachel continues to be an inspiration to us and to have a positive impact on all those that know her.
The scientific accomplishments made at the National Institutes of Health (NIH) have been eagerly anticipated by everyone involved with the ML4 Foundation. Every year, for the past four years, my husband Allan and I have brought our son Paul to the NIH to participate in the exciting research being conducted there. The day-to-day activities we are involved in are both exhilarating and exhausting. I hope this daily account of our week spent at the NIH reveals something about how an ML4-affected child's contribution can lead to wonderful scientific breakthroughs.
Sunday, June 27, 1999: We arrived at the Children's Inn on the NIH campus and were welcomed by the wonderful staff. Settling in was easy. After all, it was our fourth visit to the Inn. Paul was very happy to have a TV in the room (so was I!). After setting up the room, making the beds, and storing our food supplies in the large kitchen, we had dinner in the community dining room. Then, early to bed to prepare for our first day in the hospital.
Monday, June 28, 1999: We were given a late admission time - 11 AM - but got to the 9 West Day Hospital a little early. Paul was greeted by the nursing staff, and was immediately weighed, measured, and had Vital Signs (blood pressure, pulse and temperature) done by Joy, the R.N. assigned to us for the week. Her manner was friendly and very outgoing which was perfect for Paul, who was laughing with her in a very short time. The week-long printed schedule needed some rearranging, and Joy helped us with the changes we requested. After going through appointments with M.D.'s and therapists before, Allan and I weren't afraid to request possible changes in the schedule. The doctor who was assigned to admit us, Dr. Moore, arrived shortly after we did. I related Paul's entire 6.5 year history without missing a beat (Believe me, I've memorized every detail; Why can't they just read last year's chart??!!). Paul was very cooperative throughout the physical exam, and Dr. Moore paid close attention to my questions and concerns regarding Paul's neurological development.
After the history and physical: LUNCH! Paul's favorite part of the day was eating in the NIH cafeteria. Lunch was followed by a 2 PM rehabilitation evaluation with Dr. Perry, and a 3 PM O.T. with Becky. Becky's an old friend by now, after three evaluations, but Dr. Perry was new, meaning ANOTHER detailed story of "The Life and Times of Paul Kutner".
Dr. Perry also answered all of our questions, especially concerning Paul's new orthotics. Becky was very pleased by the progress Paul made since last year's visit, and she helped me see positive gains that I never realized were made! Allan and I were very proud of our son, and to celebrate his first day we drove into Bethesda for a great dinner at a Greek restaurant.
After Paul stuffed himself on Greek food, he had no trouble falling asleep that night. I had some time to myself, and sat on the outdoor terrace of the Inn sharing "war stories" with other parents whose children were being treated at the Clinical Center. Misery loves company, as they say.
Tuesday, June 29, 1999: Bravo to Paul!!! He made it through a 2 1/2 hour visit to the Eye Clinic like the eye-exam pro that he has become. Dr. Smith, the ophthalmologist working on the ML4 project, was able to obtain all the information, photos, data, etc. from the exam. That meant that Paul wouldn't have to undergo an exam-under-anesthesia the following day (If he was unable to complete the initial evaluation, he would have been sedated to obtain a complete exam). Allan and I had our conjunctiva "swabbed" too, so that Dr. Smith could obtain our cellular material.
After our (mandatory) snack in the cafeteria, we met with Mina, the physical Therapist who has worked with Paul before. We briefly updated her on his progress, and Mina did a thorough PT evaluation. She made recommendations regarding specific exercises for us to do and to have continued by his school therapist throughout the year.
The Neuropsych. evaluation was done at 1:30, and Paul's history was yet again related. By this time, Paul was getting restless, and Allan had to amuse him while I did the interview with the neuropsychologist. Paul wasn't too interested in the playroom's activities or the videos available in the Day Hospital, but his mood improved when the doctors came on rounds. He love to hear people discuss him! We met with Dr. Schiffman and Dr. Brady as they reviewed Paul's case with other staff involved in the ML4 project.
Finally, back to the Children's Inn for dinner. That night, we were entertained by the Kapital Klowns, a volunteer group who provided balloons, games, and face-painting for the children. The camera Paul received as a gift was put to good use.
Wednesday, June 30, 1999: Since we cancelled the 8 AM exam-under-anesthesia, the Speech Therapist, Beth, changed our 1 PM appointment to 10 AM. Beth has seen Paul every time we've come to the NIH. Her recommendations have been so very helpful to us. In 15 minutes, she had Paul biting and chewing cereal pieces better than I've ever seen. We spent an hour with Beth, then FREEDOM!!! We drove to the Inner Harbor in Baltimore and visited the Aquarium. Afterwards, Paul enjoyed the walk around the shops, dinner out, and generally being away form the hospital! We drove a very sleepy boy back to the Inn.
Thursday, July 1, 1999: We had to be at the Day Hospital at 7 AM for labwork prior to Paul having the MRSI (Magnetic Resonance Spectroscopy Imaging). This was the most stressful part of our week; Not the blood-drawing (an anesthetic cream I applied to Paul's skin prevented any pain); Not that he couldn't eat or drink (he never eats as soon as he awakens); Rather, the stress came from holding my little boy while doctors and nurses prepared to anesthetize him. The anesthesiologist, who interviewed us and examined Paul the day before, was very reassuring. Yet, although we've gone through this many times, it still remains the most difficult part of the week to deal with.
Once the procedure began, Allan and I did our NIH chores: We got our vouchers in the main lobby for our expenses, visited the gift shop (Hey, this was my summer vacation - I needed a souvenir T-shirt!!), and visited the office of Dr. Schiffman and Dr. Goldin. Dr. Goldin brought us into the lab where the ML4 research takes place, and we were able to have a brief discussion and ask questions regarding the research. Soon, our names were being called over the PA system - Paul was in the Recovery Room waiting for us to escort him to the Day Hospital. He woke up so well that we were able to take him into Washington, D.C. that afternoon to a festival on the Mall and a visit to a museum. That night, the kids at the Inn had arts and crafts for entertainment.
Friday, July 2, 1999: The last day! All that was scheduled was the photo and video session, and after filming was completed, we said our good-byes, packed our bags, cleaned our room at the Inn, and set off for a weekend at the beach. The images of the weeks spent at the NIH continue to remind me of the reason we go: To find a treatment and cure for ML4. Sure, there are difficult times we endure, such as entertaining a child for long periods between appointments, or not being happy because the appointments are too hectically placed together. But the positive images, of Paul eagerly checking his Children's Inn mailbox for the daily surprise, of seeing other children getting so much better from their treatments at the Clinical Center, of learning of advances being made for my child that allow me to hope; these are the images I remember most. I know that when the researchers attain their goals, it will be due to the contributions made by my son and the other ML4-affected children, who, with their families, have given so much of themselves. And we will continue, for as long as it takes.
My name is Tamara Goldblatt. I have a sister, Yael, who has a genetic disorder called ML4. I am 12 years old and in the sixth grade. My sister is 19 years old.
She is my closest sister. I can tell her anything and she would not tell anyone.
Even though she cannot talk like most people, she is still special to me. She signs and we talk together. Yael can understand anything you tell her. I read her books. She especially likes horror books. She likes when I dance with her to her favorite music. Sometimes we go for walks together.
Yael goes to sleepaway camp in the summer. During the year she goes to BOCES, a school for special children. She loves ice cream, cake, and other things. She is a very loving sister and likes to give people hugs and kisses. She would never fight with someone. But, I feel, if someone is mean to her, the same will come to them!!
I love my sister. She is SPECIAL!!!!!!!
The eighth-grade students at the St. Aidan's School in Williston Park, Long Island, collected money throughout December, '98 for their Mission Class charity project. Each student presented a specific charity that they felt was deserving of their donation by explaining the disorder and its affect on the lives of those who are afflicted.
Elizabeth Kiernan, a student in Ms. Waring's class, selected the ML4 Foundation as her charity. She presented the story of Paul Kutner, an ML4-affected child.
Elizabeth used photos of Paul to accompany printed information about ML4 in addition to an oral presentation. When the presentations were completed, a vote was taken, and the ML4 Foundation was selected as the recipient of a $100 check. Also, each student enclosed a letter describing how they were influenced in their choice. The letters were very sweet and moving, especially to the Kutner family. The ML4 Foundation wishes to again thank the students and teachers, especially Elizabeth Kiernan, for their kind and generous gift.
A way to double your gifts to the ML4 Foundation. You can designate the ML4 Foundation as the recipient of your Corporate Charitable donations.
For further information on how you can achieve thisplease contact Steve Schottenfeld at 973-214-2119
The forth annual ML4 Readathon kicked off in March. This year's Readathon included Millburn, Short Hills, South Orange, and Summit, N.J., with participation from the Deerfield School, and religious schools of Temple Sinai and B'nai Israel. The Readathon ran through April and raised $18,000 for ML4 research. Children raised money for ML4 based on how many books they read and how many people - parents, grandparents, aunts, uncles, neighbors and friends - they enlisted to sponsor them. For example, if a child read 10 books and a sponsor pledged 50 cents a book, $5.00 was raised from that sponsor alone. With 10 similar sponsor arrangements that child would raise $50.
Dr. Harlan Clark, Principal of the Deerfield School enthusiastically endorsed the Readathon which encourages children to read and, at the same time, gives the kids great satisfaction in helping out a worthy cause.
The top fundraiser, Jeremy Bregman of Short Hills, raised $6,130 and earned the Super Grand Prize - a round trip chauffeur driven limousine ride to and from a N.J. Nets basketball game for 4, Nintendo Game System, free passes to the Sony Movie Theaters, $50 in Toys 'R Us gift certificates, $30 in tokens to Sports 'N Games and 2 show tickets to the Paper Mill Playhouse. The other seven Grand Prize winners of N.J.Nets tickets, movie tickets, and passes to Sports 'N Games included Sam Budish, Daniel Schechner, Justen Roth, Bobby Napor, Andrew Caterfino, and Michelle and Jennifer Jacobs. All top prizes were generously donated by local businesses. Children also won prizes by reaching fundraising targets of $30 or more.
The Readathon helped raise funds, but also accomplished the very important goal of increasing awareness of ML4.
If you may be interested in helping bring the efforts of an ML4 Readathon to your child's school, please contact Steve Schottenfeld at (973) 214-2119.