Down Syndrome Division  
Linda Blevins, Division Director
Everything Grows, the newsletter for families of children with Down Syndrome and Growth Failure
January 1996
  Reprinted with the permission of The MAGIC Foundation
1327 N. Harlem Avenue, Oak Park, IL 60302-1376
1 (800) 3 MAGIC 3
(708) 383-0808 Fax: (708) 383-0899

From the Division Director: Linda Blevins
     I would like to introduce myself I am Linda Blevins, the new division director for the Down Syndrome Division. My son Jordan, who is three, has Down Syndrome. In Jordan's first year of life he plummeted from the 50th percentile to being significantly off the growth chart. We were told this was very typical of DS children and not to be concerned. Somehow, this did not ease my fears. I knew that such poor growth patterns were not healthy. I was very alarmed and began searching for answers.
     My search turned up many articles and medical abstracts detailing vitamin and amino acid disturbances, studies showing excessive free radical damage, problems with digestion and carbohydrate metabolism. Finally, I found articles on growth hormone treatment for DS by Dr. Salvadore Castells and Dr. Krystyna Wisniewski, researchers at the New York State University for Basic Research in Developmental Disabilities. I spoke with the National Down Syndrome Congress and the National Down Syndrome Society about vitamin therapy and growth hormone treatment for my son. Both organizations have policy statements that said neither treatment is necessary and the "rationale advanced for these therapies is flawed" (NDSS Update 1993).Yet, the medical research I read clearly indicated to me that DS individuals had altered metabolism and endocrine systems. What did I do with this information? I pushed on with my search.
     I shared the medical research with my pediatrician and he agreed Jordan's amino acid levels should be tested. The testing revealed many abnormalities in his amino acid regulation. Next, we traveled to California to see Dr. Jack Warner who treats DS children with vitamin therapy. Since metabolic testing can be very involved, we engaged Dr. James Heffley, a biochemist with his Ph.D. in amino acids, to interpret and make nutritional recommendations. With vitamin supplementation we began to see improvements in Jordan's health. We then changed Jordan to vitamins from NutriChem. NutriChem is a compounding pharmacy in Canada that has been formulating vitamins for children with special needs since the 1970's. This gave us the flexibility to customize the nutritional supplements for Jordan's specific metabolic requirements.
     In addition we began contacting endocrinologists. Repeatedly, doctor .after doctor-refused to see Jordan simply because he had DS. Frantically I called MAGIC. Mary Andrews was able to locate a pediatric endocrinologist in the Atlanta area who was willing to see and test Jordan for GH deficiency. Testing revealed unmeasurable IGF-1 (insulin growth factor 1) levels. IGF-1 is produced in the liver and controls; 1. growth of the long bones 2. muscle development and 3. myelination of the brain and nervous system. The next round of testing involved two pituitary stimulatory tests, which he failed. Jordan was classified as GH deficient and started on GH treatment at the age of 21 months.
     After one year of growth hormone treatment our son grew 4½ inches and over night he developed great muscle tone. His legs, arms and head circumference became proportionate to his height and weight His forehead rounded out and he developed a nasal bridge (we think brain growth caused these changes). His jaws moved into alignment and his speech levels increased. He began doing puzzles and imaginary play, his hair started growing and he grew eyelashes. Jordan's chronic reflux of undigested food suddenly stopped. He lost that pudgy DS look and we saw improvements in his metabolic tests. At 2½ years he was out of physical therapy and he did not require occupational therapy.
     Today he walks on balance beams, holds his hands over his head and tiptoes around, runs races with his sisters and draws beautiful circles. Our early intervention social worker said "Jordan is doing so well we have a difficult time keeping him in the early intervention program".
     If someone should ask me "Did growth hormone have an impact on Jordan's growth, health and cognitive skills?" They would receive an emphatic "YES!"

A big THANK YOU to Mary Andrews and the board for a terrific convention. The presenters at the medical seminars provided an abundance of information. There were many activities that revolved around the kids from the pizza party to the pool party. But my favorite was the silent auction with many unique and one of a kind items from autographed pictures and posters to walkmans and comic books. Hey Mary, why did I let that beach condo get away?! Congratulations to all those who solicited donations and worked so hard to make the convention a huge success!

The 1996 convention is not that far away. I have been entertaining ideas for possible speakers for our next convention. Dr. Wisniewski from the Institute for Basic Research, Dr. Bralley from Meta-Metrix, Dr. Thomas from Pantox, or Kent MacLeod from Nutri-Chem. I am very open to suggestions and feedback on this topic.

The convention provided a wonderful opportunity to meet with other parents who have struggled with their child's medical needs and have bucked the doctors and the insurance system. Thank you Joan Horowitz, Jamie Harvey and the other parents for sharing your stories with me. It's nice to know you're not the only one! Most importantly, it was great to finally meet those support voices on the other end of the telephone. Karen and Diedre, parents with DS kids who are working to change antiquated ideas about medical treatment concerning GH and vitamin therapy for Down Syndrome.

The real highlight of the convention for me was to meet Dr. Castells. I was thoroughly and totally impressed with Dr. Castells. He is a wonderful combination of a compassionate and competent physician, and detailed researcher. He was intelligent and funny and he had a warmth that made him very approachable and open to our many, many questions. Most importantly, you could tell that Dr. Castells motivation was genuinely from the heart and his goal is to give DS individuals the most opportunities and the best medical treatment for their endocrine problems. Dr. Castells (endocrinologist) and Dr. Wisniewski (neurologist) are the only researchers to conduct a GH clinical trial with Down Syndrome in the United States. They do continual laboratory research on DS mouse models involving GH, nerve factors and other metabolic functions. Internationally, they keep abreast of on going research and attend international conferences on DS and growth hormone. They have published many scientific articles and together have co-authored a book "Growth Hormone Treatment in Down Syndrome". Even with such busy schedules and lives, they are still available to mom's like me who have had many questions. Dr. Castells' lecture began by examining the medical position that "DS individuals are genetically short". At this point in time no gene controlling height has been located on the 21st chromosome. In addition, no chromosome controlling any aspect of growth hormone regulation has been located on the 21st chromosome. Below is a chart illustrating the genes that have been mapped that control GH regulation.

GH Growth Hormone (17)
GHRH Growth Hormone Releasing Factor (20)
IGF-1 Insulin Growth Factor-1 (15)
IGF-2 Insulin Growth Factor-2 (11)
IGF1-BP-1     Insulin Growth Factor-1-Binding Protein-1     (7)
IGF1-BP-2 Insulin Growth Factor-2-Binding Protein-1 (2)
IGF1-BP-3 Insulin Growth Factor-3-Binding Protein-1 (7)
IGF1-BP-4 Insulin Growth Factor-4-Binding Protein-1 (17)
IGF1-BP-5 Insulin Growth Factor-5-Binding Protein-1 (5)
GHR Growth Hormone Release (5)
IGF-1R Insulin Growth Factor-1 Release (15)

     If DS individuals are not genetically short, why do they have such poor growth patterns?
     Dr. Castells and Dr. Wisniewski theorize there is a dysfunction of the hypothalamus causing a neurosecretory deficiency of GH or a low spontaneous secretion of GH (J Pediatr., Intellectual Disability Research, 1992;36:29-43). The control of GH is primarily medicated through the hypothalamus, through the release of GH releasing and inhibiting factors to the pituitary (Growth Hormone, 1995 Harvery, Scane, Daughaday). In other words, the hypothalamus does not release enough GHRH (growth hormone releasing hormone) to tell the pituitary gland to release GH.
     What is the hypothalamus? It is a gland that is part of the endocrine system that controls such functions as the awake/sleep cycle, hunger and thirst and the release of GHRH. Autopsies performed on DS show a significant 50% decrease in hypothalamus size. This provides pathological evidence the hypothalamus is damaged.
     In studies conducted at The Institute of Basic Research at Staten Island (IBR), Dr. Castells found that only 10% of DS children had normal GH secretion.

Percentage   Growth Hormone Status
10%   Normal
50-55%   Severe GH Deficiency
30-35%   Mild GH Deficiency

     Dr. Castells related some results from one of the mouse studies they had performed. The study utilized a strain of mouse, the Little Mouse, which does not produce GH. The Little Mouse's brain weighs less than a typical mouse and they have normal thyroid function. The mice were given injections of GH. Tests showed an increase in the mice brain size. One cannot help but wonder if you would see the same results in DS individuals.
     What constitutes a severe or classical GH deficiency? Standard guidelines have been established by the Lawson Wilkins Pediatric Endocrine Society (LWPES)

  1. 5% or less on the growth chart*
  2. Delayed bone age (determined by x-ray).
  3. Low Somatomedian-C test (measures IGF-1 levels)
  4. Sub-normal responses to two GH stimulatory test.
*Variations by physicians criteria may range from 10% to off the growth chart.

The Lawson Wilkins guidelines and recommendations also state:
     "GH is safe and effective in treating growth failure due to GH deficiency. In the diagnosis of GH deficiency, GH test result should be interpreted in the context of the entire clinical picture. In children with classic GH deficiency, GH therapy correct a true endocrine deficiency and should be considered the standard of care: In children suspected of having subtler forms of GH deficiency, a trial of GH therapy may be warranted but the response must be carefully monitored and therapy continued only if it is demonstrably effective." (Guidelines for the Use of Growth Hormone in children, 1983).
     An issue that many parents express great interest in is the topic of leukemia. Does GH increase the risk of leukemia? The answer is...NO. Dr. Castells confirmed that not a single GH study has found a correlation between GH therapy and leukemia. While at the convention I had the opportunity to speak with the specialized pharmaceutical companies, Caremark, Quantum, Curaflex and others about the leukemia question. Each company representative verified that there was no connection between GH therapy and leukemia.
     Dr. Castells is a very thorough and cautious physician and researcher. The increased rate of leukemia that is found in the DS population, 1 out of 100, is of great concern to him. He recommends that all DS have a CBC test every 3 months. The blood test is an easy and inexpensive means to monitor changes in blood counts and can be a useful indicator for pre-leukemic conditions.
     The GH study at the IBR has ended. Dr. Castells and Dr. Wisniewski are in the process of assimilating data and publishing their results. They can say most definitely that GH helps DS children to grow, increases head circumference and improves muscle tone. Towards the end of the study an attempt was made to study the impact on cognitive development The researchers stress that this is an area where future study is required. Still, anecdotal reports from parents talk of cognitive improvements in the GH treated children.
     We at MAGIC and our DS parents anxiously await these published results. Several papers authored by Dr. Castells and Dr. Wisniewski are on file at MAGIC.

     I would personally like to thank Dr. Castells for speaking at the 1995 MAGIC convention. I greatly appreciate your vision and efforts to create a new standard of care for DS children. Keep up the good work and keep us posted on new developments.
     Another round of thank you goes to Denise Duffy. Because of Denise's direct efforts may of us have our DS children on GH. Denise originally initiated the DS division with MAGIC. Since that time the Duffy's have increased their family size with the adoption of a new daughter, Ashley. Ashley is the same size and age as Chelsea. Chelsea is a beautiful DS girl who is on GH treatment. Denise has decided to shift her emphasis and keep the home fires burning bright Good luck to you Denise and congratulations to Chelsea on her A in reading!

     In each newsletter I will present excerpts from medical articles that might be of interest The full article will be on file at the office. You may call MAGIC at 1-800-3MAGIC3 or you may call me, Linda Blevins at 1-706-638-6700.

Psychoendocrine-Immune Interaction in Down's Syndrome: Role of Zinc
Fabris, Mocchegiani and Albertini, Growth Hormone Treatment in DS

     From a physiopathological point of view, most of the homeostatic networks are found to be altered in DS subjects, namely the immune, neuroendocrine and nervous systems and the complex network regulating the turnover of nutrients, including vitamins and trace elements, the causes of such widespread alterations are still unknown, though some unifying hypotheses have recently been proposed. In particular, the existence of strict interrelationships among the major homeostatic systems, i.e. the nervous, neuroendocrine and immune networks, and the role played in these networks by a trace element in DS subjects, have led to the hypothesis that such a mineral may, at least partially be involved in some of the physiopathological features of DS.
     In the present chapter, the most relevant alterations in the homeostatic networks present in DS subjects will be reviewed and data will be reported on the beneficial effect of zinc supplementation on neuroendocrine-immune interactions m these subjects.
     This article presents two tables detailing the neuroendocrine and nutritional deficiency in DS.

Table 3
Neuroendocrine/Neurotransmitter alterations in DS
Element High      Low
GH   ++
Prolactin M +++  
Prolactin F ++  
FSH M +++  
FSH F +++  
LH M +++  
LH F +++  
TSH +++  
T4   +
T3   +
rT3   ++
IGF-1   ++
Insulin   ++
Estradiol M ++  
Opiod peptides ++  
Acetylcholine   ++
Serotonin   ++
     Brain Tissue   +++
     CSF ++  
Somatostatin   ++
Vasopressin   ++
Dopamine +  
Choline   +++
Biopterin ++  
Table 4
Nutritional Alterations (trace elements and vitamins in DS)
Element or Vitamin           High      Low
Zinc   ++
Copper ++  
Selenium ++  
Calcium +  
Iron   ++
Magnesium   ++
Manganese   ++
Aluminum ++  
Lithium +  
Lead +  
Gallium   ++
Taurine ++  
Vitamin B6   ++
Vitamin B12   +
Vitamin C   ++
Vitamin E   +

Zinc plays a crucial role for the efficiency of the three major system of homeostasis and for their physiological interaction. This trace element is present in high concentration in discrete brain areas, it is relevant for the maintenance of a physiology hormonal profile and is required to confer biological activity to thymulin, to nerve growth factor (NGF) and to immune cytokines and IL-6. Finally, no less than 200 enzymes require zinc for their efficient action.

     The observation that zinc supplementation in DS subjects is able to restore thymic endocrine activity, various immune parameters and also some hormonal factors clearly pinpoints the relevance of zinc in the maintenance of various body homeostatic mechanisms. Growth Delay in DS and Zinc Sulphate Supplementation. Napolitano, Palka, Grimaldi, Giuliani, Laglia, Calabrese, Satta, Neri & Monaco. American Journal of Medical Genetics Supplement 7:63-65(1990)
     "Children affected with DS show deficient growth, immunodeficiency, especially concerning the Tcell population and low plasma zinc levels.....The aim of this study was to evaluate if in DS children zinc sulphate therapy could improve the growth rate and affect some endocrine parameters. We studied 22 patients who received zinc sulphate for 6-9 months. Fifteen of 22 patients studied reached a higher centile in their growth rate, whereas the remaining seven showed no change, at least to date."
     The authors state that the patients experienced an accelerated growth rate, increased growth hormone serum levels and higher somatomedin serum levels. "In conclusion, zinc sulphate therapy of patients with DS affects not only the immune system, as previously reported but can also accelerate growth."

Membership and networking is extremely important Some of your best information will come through the "MOM Network." MAGIC is an organization where we can share information and pool resources. If it's out there, we will try to let you know. If some one has done it, we will match you with that person. BUT- we can only do this if you join. Your $20 plugs you in. The information in this newsletter alone is invaluable in helping you make medical decisions for your child. As a matter of fact, sign up yourself and your favorite physician too! We want them to keep abreast and up to date...

Fundraiser ideas are needed. MAGIC'S goal is to have each division self-supporting. We are encouraged to cover the cost of our mailings and expenses. In addition we have to cover the cost of a speaker for the National Convention. If you win the lottery, you know where to donate!

     In November a very important symposium was held. It was initiated by a mother in the San Diego area. The symposium featured Dr. Marie Peeters from the Lejeune Institute in Paris, MetaMetrix, a metabolic testing laboratory, Pantox, a lab specializing in oxidative stress tests, and Nutri-Chem, a compounding pharmacy that has been supplying customized vitamins since the 1970's.
     Dr. Lejeune is a brilliant man and is considered the father of human genetics. He discovered the extra 21st chromosome in DS and he discovered Fragile X. His research on DS is unparalleled! Dr. Lejeune, along with his protege Dr. Marie Peeters, have conducted vitamin and amino acid testing and clinical trials with DS individuals. Many of these results have not been published. Dr. Peeters degree of scientific credibility can not be surpassed.
     Collectively, between these organizations and institutes they have probably seen close to 1,000 amino acid profiles. Enough profiles to be able to make scientific observations and recommendations on the metabolic processes and problems of DS individuals. The seminar will be repeated on Saturday, February 24 in the Los Angeles area. Once again a MOM, Julie Bramson, will be sponsoring the seminar. She can be reached at (310) 472-8778.
     Good science dictates that you keep an open mind and participate in gaining knowledge. If from the seminar, the information that is presented is reasonable and probable, then you quantify it with a test. An overnight fasting. 40 panel amino acid profile will give you a window into your child's metabolic system. From the test, you and your doctor can make decisions on any nutritional supplementation. Don't let a doctor or national organization just say NO. The results of my son's amino acid profile convinced our doctor that Jordan had vitamin and amino acid deficiencies.
     Not everyone can travel. If you can't travel ask a friend or family member in the LA area to attend for you. Perhaps your doctor would be interested in attending or maybe he has a professional associate or colleague in LA who could go. Let your child's therapist and teacher know It's a small world, they may have friends or professional associates who could attend and provide feedback. Lastly. insist that any organization you belong to, send a representative.
     Many of you like to get your "ducks in a row" and would like to prepare for the symposium. The organizations involved will be happy to provide information. They can be reached at:

1303 Richmond Rd.
Ottawa, Ontario
Canada K2B7Y4
(613) 820-4200
FAX (613) 829-2226         
5000 Peachtree Ind. Blvd.          
Suite 110
Norcross, GA
(770) 446-5483
FAX (770) 441-2237
4622 Santa Fe Street
San Diego, CA 92109

Suggested books:
The Real Vitamin and Mineral Book. Burning and Lieberman (cost $10.00)
Thomson's Guide to Amino Acids by Lean Chaitow (cost $14.00)
Both books are written in lay terms and both contain references to DS.



A healthy, happy and prosperous NEW YEAR to all!

This newsletter has been provided as a courtesy of The MAGIC Foundation, It is for informational purposes only. The MAGIC Foundation, nor contributing physician, does not assume any liability for its content. Consult your physician for diagnosis and treatment.

  Revised: February 21, 1999.