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

About the author
I am the parent of Jenny; a cute but wild 4 year old child who happens to have an extra twenty-first chromosome. I gave birth to Jenny as I was taking my pre-med classes and thought that her having Down's would mean the end of my medical career. Luckily that was not the case; medical school in Des Moine starts in the fall of 1998.
Shortly after the infamous Day One program aired, I contacted Dixie (Lawrence) Tafoya, who started Trisomy Research Inc. (TRI). I had been doing my own library searches and believed that vitamin and mineral supplements may be able to alleviate some of the Down syndrome (DS) signs and symptoms. After doing some information searches for TRI members, I was eventually asked to join their Scientific Advisory Committee.
I remember trying to research (DS) right after Jen was born, and becoming very frustrated at the type of information that was out there. The medical research was over my head, and the stuff written for parents gave me no hope or answers. As I have taken more classes and spent time in the medical library, I have become more familiar with the medical language in the scientific journals. I see my old frustration in the eyes of parents who are so desperate for information and understanding. That is why I started this newsletter; to take the research in the medical journals and put it into everyday language.
In addition to Jenny, I have 2 other children, Lyndsey (7) and Tanner (3). I also have an above-average spouse named Mark, who will also be attending medical school next year.

Thanks to Colleen MacRae for the proofing help!

About the Newsletter
This newsletter has a mission; to provide up-to-date medical research about Down syndrome. While the articles will be written in language most parents can understand, the research will be referenced so readers can go to the original source.

What could be in each issue?

While I certainly have my opinions, this newsletter will not push TNI or any other treatment.

This edition contains DS info on: AAI, Zinc, Alzheimer's in mothers of DS children, teeth, smelling, tonsillectomies and some basic biochemistry on amino acids and proteins.
Next Issue - SOD-1, free radicals, antioxidants, some basic biochemistry on lipids and more.

There is a conference relating to DS (heavy on TNI and Piracetam) scheduled May 2 in Saratota, FL. Email Mary Smith at flsmith@gte.net or call 914-755-7325 for more info.

Zinc is deficient in DS
Zinc has dozens of uses in the body including growth, immune function, sexual development, DNA synthesis and thyroid functioning. Zinc is a cofactor for over 100 enzymes. Many studies have shown that DS children have significantly lower serum (blood) levels of zinc than do "normals"*.

Zinc Supplementation has benefits
Different studies have shown that giving DS children added zinc has the following benefits:

  1. a significant increase in DNA synthesis
  2. a decrease in infections
  3. a normalizing effect on lymphocyte response (before zinc was added, lymphocytes from DS children were not reacting normally to certain agents)
  4. a normalizing effect on thyroid hormones was found in one study. However, a more recent report looked at five DS children who had thyroid abnormalities. All were zinc deficient, but only one had a normalizing of thyroid activity with zinc supplements alone.
None of the MedLine research showed contradictions to these findings. Also, no serious side effects were reported.
It is not known exactly why DS kids are deficient in zinc. Absorption problems may be one explanation. Another is that zinc is a cofactor in the enzyme SOD-1, which is overproduced in DS. The SOD-1 binds zinc, and its over expression may leave too little for the rest of the body.
Another issue with zinc is antibiotics. Use of them, especially those that are sulfa based, can cause zinc deficiencies.

What to consider with supplements
Zinc competes with other minerals for absorption, so over doing it with zinc may cause deficiencies of other nutrients.
Of course, with any treatment, this should be discussed with your physician so that proper dosage and contraindications can be communicated.
Dietary sources of zinc include meat, eggs, seafood and soy products.

     Bjorksten, B. et al.(1980). Zinc and immune function in Downs syndrome. Acta-Paediatr -Scan. 69(2). 183-7.
     Bringo, et al.(1996). Normalization of cellular zinc levels in patients with Downs syndrome does not always correct low thymulin levels. Acta-Prediatr. 85(11). 1370-2.
     Licastro, F., Mocchegiani, E., Masi, M., & Fabri, N. (1993). Modulation of the neuroendocrine system and immune functions by zinc supplementation in children with Down's syndrome. J. Trace Elem.-Electrolytes. 7(4). 237-9.
     Licastro, F., et al. (1994) Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J-Intellectual-Dis-R. 38 (pt 2). 149-62.
     Stabile, et al (1991) Immunodeficiency and plasma zinc levels in children with Downs Syndrome: A long-term follow-up of oral zinc supplements. Clin-Immunol-Immunopathol. 58(2). 207-16.

* "Normals" is a term used in the literature to describe those who do not have the disease being studied. While it may look politically incorrect, it reflects the terminology.

Atlantoaxial Instability (AAI) is defined as too much mobility between the 1st and 2nd cervical vertebra. It is usually found by X-ray (both a neutral and a flexed position) and is diagnosed if there is a space of more than 4 mm between C1 and C2. 15% of DS children have AAI, but nearly all have no symptoms.
The Special Olympics screens DS individuals prior to participation in their events and those with AAI are severely restricted in their activities, even if they are asymptomatic. However, it is questionable as to whether AAI is that simple to diagnose, and if those who are asymptomatic should be restricted in their activities.

Can X-rays diagnose AAI?
The research is conflicting. One study X-rayed 19 DS kids, and did it again 10 minutes later. While 6 had C1/C2 spaces of >4mm, only 3 showed that on both films. Other studies show more reliability. One followed 141 kids with AAI long term. 92% of them had films that were similar to their first one after 5 years. Computerized Tomography is another way to find AAI. It shows more detail and diagnoses more spinal compression than X-ray, but costs more.

Implications of an AAI diagnosis
With all the DS individuals who have AAI, there are only 41 reported cases that are symptomatic. Of those 41, only 3 were reported to have worsening of symptoms after a sports trauma.
In two studies that followed a total of 236 DS kids with asymptomatic AAI, only one became symptomatic after a sports injury. Another study looked at 91 asymptomatic AAI/DS kids. They split the group in 2, allowing one group to participate in "risky" sports, and restricting activity in the other. After one year, there were no differences between the groups in neurological signs or C1/C2 distance.

While the large majority of cases are asymptomatic, the symptomatic victim may exhibit difficulty walking, abnormal gait, sensory deficits, head tilt, clumsiness, and other neurological problems. Treatment usually includes re-evaluation (for those with or without symptoms), limiting activities that could injure the neck, and fusing the C1/C2 together for severe problems.
Recommendations are to have DS children X-rayed for AAI before age 3. There is debate as to limiting activities with asymptomatic AAI, but most experts agree to limit those who are symptomatic. Remember to remind surgeons/anesthesiologists about the possibility of AAI prior to surgery so they can take extra care with the patient's neck.

My Experience
Jen did have a head tilt, so we had her X-rayed at age 3 prior to gymnastics. It did show AAI. However, she was less than cooperative during the films which could have made them invalid. We waited with gymnastic and had X-rays again at age 4 that were normal. Who knows if it was really AAI that cleared up or a case of bad films.

     American Academy of Pediatrics (1995) Atlantoaxial instability in Down Syndrome: Subject review. Pediatrics. 96(1) 151-4.
     Cremers, M., Bol-E., de-Roos, F., van-Gijn, J.(1993) Risk of sports activity in children with Down's Syndrome and Atlantoaxial instability. Lancet 342( 8870) 511-14.
     Cremers, M., Ramos, L., Bol-E, van-Gijn, J. (1993) Radiological assessment of the Atlantoaxial distance in Down's syndrome. Arch-Dis-Child 69(3) 347-50.
     Levy, M. & McComb, J. (1996) c1-c2 fusion in children with antlantoaxial instability and spinal cord compression: technical note. Neurosurgery 38(1) 215-16.
     Pueschel, S., Moon, A., Scola, F. (1992) Computerized tomography in persons with Down syndrome and atlantoaxial instability. Spine 17(7) 735-7.
* A very comprehensive review of the literature if you want to learn more.

Upper Airways in DS
Will those teeth ever come in? It was not your imagination that it took longer than normal for your child with DS to get teeth . Not only do DS children get their teeth at an older age, they have to "work at them" longer. Of course that means increased misery for child and parent.
As for permanent teeth, they come in smaller and are often abnormally shaped.
DS children also have an increased rate of periodontal disease, so careful cleaning and frequent dentist visits are recommended.

Tonsillectomies and adnoidectomies are frequently recommended for DS children to relieve symptoms of upper airway obstruction and sleep apnea. (Sleep apnea is when someone stops breathing for short periods of time during sleep.)
While normals usually have these surgeries done on an outpatient basis, DS kids had an average hospital stay of 2.1 days following those surgeries. More troubling is that 25% had to spend time in ICU. 60% of the DS had some respiratory problem after surgery which was usually corrected by giving the patient oxygen.

Two studies recently looked at the smelling abilities in those with DS. While adolescents with DS showed no difference compared to normals, deficits were found in those over 40 years of age. Specifically, odor detection threshold, odor identification and odor memory were decreased significantly in the older group. While the cause is not known, these researchers suspected dementia was possibly to blame.

     Bower, C. & Richmond, D. (1995). Tonsillectomy and adnoidectomy in patients with Down syndrome. Int-J-Pediatr-Otorhinolaryngol. 33(2). 141-8.
     McKeown, D. et al. (1996). Olfactory function in young adolescents with Down's syndrome. Neurol-Neurosurg-Psychiatry. 61(4). 412-24.
     Murphy, J. & Jinich, S. (1996). Olfactory dysfunction in Down's syndrome. Neurobiol-Aging. 17(4). 631-7.
     Peretz, B. et al. (1996). Modification of tooth size and shape in Down syndrome. J-Anat. 188. 167-72.
     Reuland-Bosma, W. (1995). Down Syndrome. Oralfacial Aspects. Rev-Belge-Med-Dent (French). 50(3). 53-62.

Comprehensive Evaluations & Treatment
Dr. Leichtman is a pediatrician/geneticist who practices in the Virginia Beach, VA area who specializes in clinical genetics and disability management.
Dr. Leichtman has seen hundreds of individuals with DS, autism, and other genetic disorders . The patient can expect a thorough evaluation with the goal of creating a treatment plan appropriate for the family and the patient. That might include prescription meds, supplements, traditional therapies, etc. For more information, call his office at 757-460-1919 or email larry@lleichtman.org.

DS Moms at risk for one type of Alzheimer's disease
Most of us know that DS adults are more likely to get Alzheimer's disease (AD) than the normal population. These authors of this research looked at the risk of the parents of getting the same ailment. They compared parents of non-DS mentally retarded children to parents who had DS children. Moms of DS children had a five times higher rate of early-onset AD than the other group. (Early-onset AD often strikes in the patient's 40's or 50's instead of later in life with the late-onset AD.)
There was no difference between the moms with late-onset AD, nor was there any difference between either group of dads. The early-onset form of AD does have a higher genetic cause, which may explain the risk.

     Schupf, N. (1994, Aug. 6). Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome. Lancet. 344 (8919), 353-6.

This is your absolutely-free-no-obligation-premier-edition of 3.21 It will be mailed to hundreds of people in the US and 2 other countries!
If you would like to subrscibe to future editions, please follow theses instructions; send your name/address and a check or money order in US funds to:
Karalee Wetzel, 675 35th St. Des Moines IA 50312
The subscription rates for 5 editions (one year) are:

  1. Parent/family member in US - $18.00
  2. Parent/family member outside US - $22.00
  3. Organization/professionals in US - $25.00
  4. Organization/professionals outside US - $29.00

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

Places to donate money or get information regarding DS:
Friends of TRI, 11718 Barrington Ct #511, Los Angeles, CA 90049
National Down Syndrome Society (NDSS), 666 Broadway, New York, NY 10012
National Down Syndrome Congress (NDSC), 1370 Center Drive, Suite 102, Atlanta, GA 30338

  Revised: July 1, 1999.