3.21 Three two one  
3.21 A newsletter that examines the medical aspects of Down syndrome
Vol. 1, No. 4, August 1998
  Reprinted with the permission of Karalee Wetzel

Research Is Ready
The research done by Jill James regarding the MTHFR gene defect in moms of children with DS is ready to publish. Until it is in print, nothing can be reported, but as soon as I am given the go ahead you will get all the details.

Prozac and DS
Jen was started on Prozac for her autism in April to decrease her compulsive behaviors. It took awhile but eventually seemed to decrease her compulsions. Her speech has increased dramatically, especially her spontaneous speech. She had a ton of words stored and they are starting to come out. In addition, she is no longer avoiding eye contact with other people.
Other parents who have put their children with DS on Prozac (often for constipation) have seen similar speech improvements.
Prozac is called an SSRI. It works by blocking the cell from taking serotonin "up" and breaking it down. While there has been little research on serotonin in DS, there has been some that suggests that it is low in DS. That could explain the effect Prozac seems to have.
Rumor is some of the DS researchers are interested in doing a study at some point.

Surgery Complications in DS
Another study that looked at problems following tonsillectomy or adenoidectomy was just released. Compared to normals, children with DS were 5 times more likely to have respiratory problems that required some type of intervention. In addition, the time on IV fluids following surgery was longer in the DS group at 23.5 hrs vs. 16 hrs in non DS children.
Given the frequency of problems, the authors of this study recommended that children with DS be kept in the hospital over night after such a surgery.

     Goldstein, N.A. et al. Postoperative complications after tonsillectomy and adenoidectomy in children with Down syndrome. Arch Otolaryngol Head Neck Surg, 124(2), 171-6.

This Issue
Diabetes and the connections to DS, Growth hormone, 5-hydroxy tryptophan, complications after minor surgeries.

Next Issue
Leukemia, more on Alzheimer's disease, different non-drug treatments

Diabetes and DS - 2 connections
Using data from previous epidemiological studies, this report calculates the rate of Type 1 diabetes is between 1.4% to 10.6% in the population with DS. That is much higher than the normal population. However, those with DS seemed to control their diabetes better than the normal population. Most were able to keep sugar levels as stable with 1 insulin injection per day as normals did with multiple injections. The only explanation the authors gave was that perhaps the population with DS lives a more stable lifestyle.

Gestational Diabetes
Gestational diabetes hits when a woman is pregnant and usually goes away after the child is born. One hospital looked at the 22,300 births at their facility over a 7 year period to find the risk of having a baby with DS in the moms who had different types of diabetes. Women with gestational diabetes were 2.75 times more likely to have a baby with DS that a mom without that form. Women who already had diabetes before conception had no babies with DS.
Since the DS chromosomal error occurs prior to or at conception, having gestational diabetes could not cause someone to have a baby with DS. Two other explanations are that 1) the fetus with DS somehow pushes mom to diabetes or 2) whatever creates the risk for a mom to conceive a child with DS creates a risk for getting diabetes. The latter seems more likely.
Future research should look at other pregnancies in the women with gestational diabetes who had a baby with DS.

     Anwar, A. et al. (1998) Type I diabetes mellitus and Down's syndrome: prevalence, management and diabetic implications. Diabet-Med. 15 (2), 160-3.
     Narchi, H. & Kulayat, N. (1997) High incidence of Down's syndrome in infants of diabetic mothers. Arch Dis Child. 77(3), 242-4.

5-Hydroxy Tryptophan
This chemical is a precursor to serotonin. Years ago it looked promising as a treatment for DS, mainly because some research indicated that children with DS had lower serum levels of serotonin. Bazelon et.al (1967) found that children with DS who were given 5-hydroxy tryptophan had less tongue protusion and hypotonia, had more activity and higher Baily(development) scores. However, the long term reports showed no difference over a long period of time. Weise et.al (1974) gave infants with DS 5-hydroxy tryptophan until ages 3 or 4. While the group given it did have a small advantage in overall development compared to the control group did, it was not statistically significant. That would imply it had a small effect or the difference was due to chance.

     Bazelon, M. et al. (1967) Reversal of hypotonia in infants with Down syndrome by administration of 5-hytroxytryptophan. Lancet 1, 1130-33.
     Weise, et al. (1974) The use of 5-HTP in the treatment of Down's syndrome. Pediatrics. 54, 165-68.

Growth Hormone in DS
Another very controversial treatment has been the use of human growth hormone (GH). Studies done in the 60's claimed higher intelligence, developmental improvements, etc. in children with DS who were treated with it. In general, the results did not pan out for those aspects over time.
I had heard from informed sources that (GH) can increase the risk of leukemia in children with DS. (Children who who have DS already have an increased risk of developing leukemia.) However, I was unable to find that on my Medline search even looking back into the database from the 1960's.
We all know that children with DS are shorter than normal. What is known about their hormone function when it comes to growth? Can GH help and be safe?
First, you may want to look at Biochem 101 before continuing if you are not up on how the growth hormone system works. Basically, the body tells the hypothalamus gland it requires a certain hormone. The hypothalamus sends out that hormone's releasing hormone, which travels to the pituitary and tells it to release the hormone. After GH is released into the body, it gets other cells to produce Insulin-like Growth Factor (which are subdivided into IGF-1, IGF-2, etc.). IGF's then travel to cells of bone and other tissue and gets them to proliferate.
Several substances substances can stimulate the release of GH. Two are levodopa and clonadine. They are usually given to children who are suspected of a GH problem to test if the hormone is being released or not. Children with DS seem to have disparities in the results of these two tests. 20 children with DS were given these two tests, and 12 of those had conflicting results. 5 of those children had low GH after levodopa and 6 had low levels after chlonidine. (The last one had strange results in other hormones related to GH.) (Castells, 1992) Another study only found deficits in GH levels after the clonidine test (Pueschel, 1993).
Some findings have discovered that children with DS seem to have their pituitaries "fully stocked" with GH, so it is being manufactured and stored. There does seem to be two problem points. One is that GH is not getting released in high enough levels. The other is a IGF-1 shortage in many of the children with DS who were tested (Beccaria, 1998). The last problem may be dependant or independent on the decrease of GH being released.

GH treatment was bigger in the 60's and 70's for DS than it is today. However, there are a number of research articles written in the 1990's about the subject, which indicates it may be making a come-back. The general consensus of the research is that GH does seem to be effective in stimulating growth and it seems to be safe.
One study started giving GH to infants (mean age 7.4 months) and continued for three years. While these infants started at the 50th percentile for height on the DS growth chart, at the end of the study they were in the 95 percentile. Head circumference was also affected, but not to the extent of height (Annerén, 1993). A study was done by the same researcher on 5 children with DS age 3.5 to 6.5 years. After 6 months, the children's growth velocity (rate of growth) increased from a starting range of 2.3 to 2.8 cm/6 months to a range of 3.3 to 5.8 cm/6 months. Their levels of IGF -1 and IGF-2 both increased with the treatment, although only the IGF-1 was below normal before treatment (Annerén, 1986). Development was not measured in either of these studies.
This option of treatment is rarely taken by parents. First, it is extremely expensive -many thousands of dollars per year and it is rarely covered by insurance. Secondly, it seems to only have a cosmetic improvement in the children given GH. While there may be other improvements, no research has been able to really prove it. Third, many physicians will not go along with the therapy. Finally, no long term studies have been done regarding side effects after treatment.
I recently spoke to a mom who has a child with DS and autism (age 4). This child has been on GH for 5 months. He grew 3 inches in that time and had a slight increase in head circumference. The mom also believed he had an increase in muscle tone.
Like the other handful of treatments that have been tried with DS, it seems this one needs to be studied more.

     Annerén, G., et al. (1986) Growth and somatomedin response to growth hormone in Down's syndrome. Arch Dis Child 61(1) 48-52.
     Annerén, G., et al. (1993) Normalized growth velocity in children with Down's syndrome during growth hormone therapy. J Intellect Disabil Res 37(4) 381-7.
     Beccaria, et al. (1998) Further evidence of choligerngic impairment of the neuroendocrine control of GH secretion in Down's syndrome. Dement Geriatr Cogn Disord 9(2) 78-81.
     Castells, S. et al. (1992) Growth hormone deficiency in Down's syndrome children. J Intellect Disabil Res 36(1) 29-43.
     Pueschel, S.M. (1993) Growth hormone response after administration of L-dope, clonidine and growth hormone releasing hormone in children with Down syndrome. Res Dev Disabil 14(4), 291-8.

Flies exposed to CO2 have high incidence of nondisjunction
Female flies (drosophila) were exposed to carbon dioxide (CO2) at different stages of their reproductive cycle. When exposed at meiosis 1 (when the egg is mature and ovulated) the batch of flies had a 100-fold increase in nondisjunction compared to the control. The second batch of "babies" born to the exposed females had no increase in chromosomal abnormalities. That would imply that the immature eggs were not affected by the CO2. This study also implies that what happens to a female (fly) just prior to conception is what determines normal cell division in the egg. BTW - this article stated that this may support the theories about the increases in DS births after the Chernobyl nuclear accident.

     Fujikaxa, K. et al. (1998) High production of nondisjunction mutants in the offspring of Drosophila females exposed to carbon dioxide at meiosis 1. Environ Mol Mutagen 31(2), 176-82.

This newsletter is not associated with any organization.
The information in 3.21 is not intended as medical advice. Discuss any treatments with your physician.

To subscribe to 3.21 for 5 issues, send $18 in US/$22 outside for family, $25 in US/$29 outside for organizations to:
Karalee Wetzel, 675 35th St, Des Moines IA 50312

Conference regarding nutritional aspects in DS
There will be a conference focusing on the nutritional aspects and treatments of Down syndrome in Huntsville, Alabama. The date is September 26 and the speakers include: Dr. Larry Leichtman (pediatrician), Dr. David Swenson (biochemist), and parents.
For more information please call Kim at 256-880-2398. The cost is only $15 to attend.
I have gone to a few and they are informative and inspiring.

  Revised: July 1, 1999.