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    Down?s Syndrome (Holistic)

    Down?s Syndrome (Holistic)

    About This Condition

    Enjoy a higher quality of life by managing the medical conditions often associated with this genetic disease. According to research or other evidence, the following self-care steps may be helpful.
    • Think zinc

      With a doctor's supervision, improve immune function, reduce infection rates, and stimulate growth by taking 1 mg per 2.2 pounds (1 kg) of body weight per day, along with a copper supplement providing 1 to 3 mg per day, as recommended by a doctor

    • Get some extra E

      Check with a nutritional health professional for advice on taking 100 to 400 IU per day vitamin E to improve antioxidant protection

    • Discover acetyl-L-carnitine

      Take 500 mg of this nutritional supplement three times per day to improve visual memory and attention

    • Get a checkup

      Work with a qualified healthcare provider to find out if celiac disease or other causes of food sensitivities may be compromising nutritional health

    • Work in a workout

      Increase physical activity to improve strength and endurance that can be compromised in people with Down?s syndrome

    About

    About This Condition

    Down?s syndrome is a genetic abnormality caused by a defect of chromosome 21. People with Down?s syndrome have varying degrees of cognitive and developmental disabilities and suffer from a wide array of other symptoms, such as premature aging with development of Alzheimer?s disease before the age of 40, short stature and flaccid musculature, frequent infections, autoimmune disease, hypothyroidism, leukemia, and heart defects.1

    Down?s syndrome is the most common genetic disorder, occurring at a rate of about one in 700 to 800 births.2

    Symptoms

    Newborns with Down?s syndrome may be lethargic, rarely cry, and have extra skin around the neck. Children and adults with Down?s syndrome may have slanted eyes, flattened nose, large tongue, small ears, short fingers, and broad hands, and may have difficulty performing routine activities of daily life.

    Healthy Lifestyle Tips

    A number of studies have examined the nutritional status of children with Down?s syndrome. These children consume lower amounts of calories but are more likely to be obese and to have specific nutrient deficiencies in their diets.3 , 4 Malabsorption is thought to contribute to the health consequences of Down?s syndrome, such as cardiovascular disease and Alzheimer?s disease , and in a small preliminary study, stool analyses showed that all of four Down?s syndrome patients examined had insufficient digestion.5 Researchers have long suggested that gluten sensitivity may be a cause for malabsorption in many Down?s syndrome patients.6 , 7 Many recent studies have established a link between Down?s syndrome and celiac disease .8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 The immune systems of individuals with celiac disease produce antibodies to gliadin, a protein from wheat gluten and some other grains, and these antibodies damage the intestines resulting in malabsorption and diarrhea . The treatment for celiac disease is complete avoidance of dietary gluten. The prevalence of celiac disease among people with Down?s syndrome in these studies ranged between 3.9% and 16.9%, more than 100 times the prevalence in the general population. Antibodies to gliadin have been found to be elevated in many people with Down?s syndrome who do not express the severe symptoms of celiac disease.18 , 19 , 20 , 21 One study found antibodies to proteins from egg and dairy to be elevated in a high percentage of Down?s syndrome patients.22 Patients with Down?s syndrome should be evaluated by a doctor for these types of food sensitivities , as well as for celiac disease.

    A comparison study found that children with Down?s syndrome were likely to have less physical activity than other children, suggesting that the condition itself may not be responsible for the tendency toward obesity .23 In another study, adults with Down?s syndrome were more likely to be obese if they had poor social connections, even after the effects of physical activity and diet were taken into account.24 People with Down?s syndrome were found to have lower muscle strength and lower bone mineral density than both healthy individuals and people with mental retardation but without Down?s syndrome. These findings have led researchers to emphasize the importance of physical training for individuals with Down?s syndrome.25 Although some studies have found that people with Down?s syndrome do not benefit as much from exercise as people without Down?s syndrome,26 , 27 , 28 intervention trials have found that those who become physically active do improve in strength and endurance.29 , 30 Cardiac effects of Down?s syndrome, such as mitral valve prolapse , may reduce the exercise capacity of these individuals.31 Exercise has been suggested as a preventive measure to improve blood flow to the brain and to protect against Alzheimer?s disease, because people with Down?s syndrome have a high risk for developing this disease at a young age.32 This potential benefit of exercise, however, has not yet been tested.

    Supplements

    What Are Star Ratings?

    Our proprietary ?Star-Rating? system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by some in the medical community, and whether studies have found them to be effective for other people.

    For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

    3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

    2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

    1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

    Supplement Why
    3 Stars
    Zinc
    1 mg per 2.2 lbs (1 kg) of body weight daily
    Learn More

    Blood levels of the antioxidant minerals selenium and zinc were normal in one study of people with Down?s syndrome,33 but others have found selenium34 , 35 and zinc36 , 37 , 38 levels to be low. In some studies more than 60% of patients with Down?s syndrome had low zinc levels.39 , 40 A preliminary study of selenium supplementation in children with Down?s syndrome found that the antioxidant activity in the body improved; however, the implications of this finding on the long-term health of these people is unclear.41 Zinc is critical for proper immune function, and in one preliminary study the majority of patients with Down?s syndrome examined had low zinc levels and low immune cell activity. Supplementation with zinc resulted in improved immune cell activity.42 In preliminary intervention trials, improved immune cell activity was associated with reduced rates of infection in Down?s syndrome patients given supplemental zinc in the amount of 1 mg per 2.2 pounds of body weight per day.43 , 44 A controlled trial, however, did not find zinc, at 25 mg daily for children under 10 years of age and 50 mg for older children, to have these benefits.45 Zinc has other roles in the body; preliminary data have indicated that zinc supplementation, at 1 mg per 2.2 pounds of body weight per day, improved thyroid function in Down?s syndrome patients,46 , 47 , 48 and increased growth rate in children with Down?s syndrome.49

    2 Stars
    Acetyl-L-Carnitine
    500 mg three times per day
    Learn More

    Acetyl-L-carnitine is a compound that occurs naturally in the brain and plays a role in the normal functioning of the nervous system. In a preliminary trial, patients with Down?s syndrome were given 500 mg of L-acetyl-carnitine three times daily for 90 days and were observed to improve in visual memory and attention. Similar improvement was not seen in untreated patients, nor in patients with mental deficiency unrelated to Down?s syndrome who were also given L-acetyl-carnitine.50 More research into the effects of L-acetyl-carnitine in people with Down?s syndrome is needed.

    2 Stars
    Vitamin E
    100 to 400 IU daily
    Learn More

    Alzheimer?s disease , cataracts , autoimmune diseases, and a general increase in the pace of aging are all seen in people with Down?s syndrome.51 These associated conditions are similar in that they involve damage to body tissues by free radicals. It is believed that the genetic defect that produces Down?s syndrome increases the need for antioxidants (nutrients that prevent free-radical damage), and several studies of blood and urine biochemistry have shown this to be true.52 , 53 In a preliminary study, vitamin E protected cells of people with Down?s syndrome from the oxidative damage to which they are most susceptible.54 However, blood levels of vitamin C and vitamin E , two antioxidant nutrients, have not been found to be different when compared with those of healthy individuals.55 , 56 The role of vitamin E and other antioxidants in treating Down?s syndrome needs further exploration.

    1 Star
    Folic Acid
    Refer to label instructions
    Learn More

    The red blood cells of people with Down?s syndrome are unusual in ways that suggest either vitamin B12 or folic acid deficiency.57 , 58 , 59 However, folic acid levels have been found to be normal in each of these studies, and only one study has found lower levels of vitamin B12 in Down?s syndrome as compared with healthy individuals.60 Intervention trials using either vitamin B12 or folic acid have not been done.

    1 Star
    Multivitamin
    Refer to label instructions
    Learn More

    In a double-blind trial, improvement was reported in the intellectual functioning of five children with Down?s syndrome given a daily high-potency multivitamin-mineral supplement .61 This sparked interest in further research, but in a larger double-blind trial that followed, no benefit was observed.62 A later controlled trial found that multivitamin and mineral supplementation had no greater effect than did placebo in children with Down?s syndrome.63 A review of the research found no compelling reason to give multivitamin or B vitamin supplements to people with Down?s syndrome.64

    1 Star
    Selenium
    Refer to label instructions
    Learn More

    Blood levels of the antioxidant minerals selenium and zinc were normal in one study of people with Down?s syndrome,65 but others have found selenium66 , 67 and zinc68 , 69 , 70 levels to be low. In some studies more than 60% of patients with Down?s syndrome had low zinc levels.71 , 72 A preliminary study of selenium supplementation in children with Down?s syndrome found that the antioxidant activity in the body improved; however, the implications of this finding on the long-term health of these people is unclear.73 Zinc is critical for proper immune function, and in one preliminary study the majority of patients with Down?s syndrome examined had low zinc levels and low immune cell activity. Supplementation with zinc resulted in improved immune cell activity.74 In preliminary intervention trials, improved immune cell activity was associated with reduced rates of infection in Down?s syndrome patients given supplemental zinc in the amount of 1 mg per 2.2 pounds of body weight per day.75 , 76 A controlled trial, however, did not find zinc, at 25 mg daily for children under 10 years of age and 50 mg for older children, to have these benefits.77 Zinc has other roles in the body; preliminary data have indicated that zinc supplementation, at 1 mg per 2.2 pounds of body weight per day, improved thyroid function in Down?s syndrome patients,78 , 79 , 80 and increased growth rate in children with Down?s syndrome.81

    1 Star
    Vitamin B12
    Refer to label instructions
    Learn More

    The red blood cells of people with Down?s syndrome are unusual in ways that suggest either vitamin B12 or folic acid deficiency.82 , 83 , 84 However, folic acid levels have been found to be normal in each of these studies, and only one study has found lower levels of vitamin B12 in Down?s syndrome as compared with healthy individuals.85 Intervention trials using either vitamin B12 or folic acid have not been done.

    References

    1. Reading CM. Down?s syndrome: nutritional intervention. Nutr Health 1984;3:91?111 [review].

    2. Teksen F, Sayli BS, Aydin A, et al. Antioxidative metabolism in Down syndrome. Biol Trace Elem Res 1998;63:123?7.

    3. Luke A, Sutton M, Schoeller DA, Roizen NJ. Nutrient intake and obesity in prepubescent children with Down syndrome. J Am Diet Assoc 1996;96:1262?7.

    4. Chad K, Jobling A, Frail H. Metabolic rate: a factor in developing obesity in children with Down syndrome? AmJ Ment Retard 1990;95:228?35.

    5. Abalan F, Jouan A, Weerts MT, et al. A study of digestive absorption in four cases of Down?s syndrome. Down?s syndrome, malnutrition, malabsorption, and Alzheimer?s disease. Med Hypotheses 1990;31:35?8.

    6. Reading CM. Down?s syndrome: nutritional intervention. Nutr Health 1984;3:91?111 [review].

    7. Storm W. Prevalence and diagnostic significance of gliadin antibodies in children with Down syndrome. Eur J Pediatr 1990;149:833?4.

    8. Zubillaga P, Vitoria JC, Arrieta A, et al. Down?s syndrome and celiac disease. J Pediatr Gastroenterol Nutr 1993;16:168?71.

    9. Castro M, Crino A, Papadatou B, et al. Down?s syndrome and celiac disease: the prevalence of high IgA-antigliadin antibodies and HLA-DR and DQ antigens in trisomy 21. J Pediatr Gastroenterol Nutr 1993;16:265?8.

    10. Jansson U, Johansson C. Down syndrome and celiac disease. J Pediatr Gastroenterol Nutr 1995;21:443?5.

    11. George EK, Mearin ML, Bouquet J, et al. High frequency of celiac disease in Down syndrome. J Pediatr 1996;128:555?7.

    12. George EK, Mearin ML, Bouquet J, et al. Screening for coeliac disease in Dutch children with associated diseases. Acta Paediatr Suppl 1996;412:52?3.

    13. Bonamico M, Rasore-Quartino A, Mariani P, et al. Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies. Acta Paediatr 1996;85:1503?5.

    14. Gale L, Wimalaratna H, Brotodiharjo A, Duggan JM. Down?s syndrome is strongly associated with coeliac disease. Gut 1997;40:492?6.

    15. Carlsson A, Axelsson I, Borulf S, et al. Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome. Pediatrics 1998;101:272?5.

    16. Hansson T, Anneren G, Sjoberg O, et al. Celiac disease in relation to immunologic serum markers, trace elements, and HLA-DR and DQ antigens in Swedish children with Down syndrome. J Pediatr Gastroenterol Nutr 1999;29:286?92.

    17. Pueschel SM, Romano C, Failla P, et al. A prevalence study of celiac disease in persons with Down syndrome residing in the United States of America. Acta Paediatr 1999;88:953?6.

    18. Castro M, Crino A, Papadatou B, et al. Down?s syndrome and celiac disease: the prevalence of high IgA-antigliadin antibodies and HLA-DR and DQ antigens in trisomy 21. J Pediatr Gastroenterol Nutr 1993;16:265?8.

    19. Lazzari R, Collina A, Arena G, et al. Celiac disease in children with Down?s syndrome. Pediatr Med Chir 1994;16:467?70 [in Italian].

    20. Bonamico M, Rasore-Quartino A, Mariani P, et al. Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies. Acta Paediatr 1996;85:1503?5.

    21. Carlsson A, Axelsson I, Borulf S, et al. Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome. Pediatrics 1998;101:272?5.

    22. Kanavin O, Scott H, Fausa O, et al. Immunological studies of patients with Down?s syndrome. Measurements of autoantibodies and serum antibodies to dietary antigens in relation to zinc levels. Acta Med Scand 1988;224:473?7.

    23. Sharav T, Bowman T. Dietary practices, physical activity, and body-mass index in a selected population of Down syndrome children and their siblings. Clin Pediatr 1992;31:341?4.

    24. Fujiura GT, Fitzsimons N, Marks B, Chicoine B. Predictors of BMI among adults with Down syndrome: the social context of health promotion. Res Dev Disabil 1997;18:261?74.

    25. Angelopoulou N, Matziari C, Tsimaras V, et al. Bone mineral density and muscle strength in young men with mental retardation (with and without Down syndrome). Calcif Tissue Int 2000;66:176?80.

    26. Eberhard Y, Eterradossi J, Therminarias A. Biochemical changes and catecholamine responses in Down?s syndrome adolescents in relation to incremental maximal exercise. J Ment Defic Res 1991;35:140?6.

    27. Pitetti KH, Climstein M, Campbell KD, et al. The cardiovascular capacities of adults with Down syndrome: a comparative study. Med Sci Sports Exerc 1992;24:13?9.

    28. Millar AL, Fernhall B, Burkett LN. Effects of aerobic training in adolescents with Down syndrome. Med Sci Sports Exerc 1993;25:270?4.

    29. Millar AL, Fernhall B, Burkett LN. Effects of aerobic training in adolescents with Down syndrome. Med Sci Sports Exerc 1993;25:270?4.

    30. Peran S, Gil JL, Ruiz F, Fernandez-Pastor V. Development of physical response after athletics training in adolescents with Down?s syndrome. Scand J Med Sci Sports 1997;7:283?8.

    31. Pueschel SM, Werner JC. Mitral valve prolapse in persons with Down syndrome. Res Dev Disabil 1994;15:91?7.

    32. Crawford JG. Alzheimer?s disease risk factors as related to cerebral blood flow. Med Hypotheses 1996;46:367?77 [review].

    33. Teksen F, Sayli BS, Aydin A, et al. Antioxidative metabolism in Down syndrome. Biol Trace Elem Res 1998;63:123?7.

    34. Kadrabova J, Madaric A, Sustrova M, Ginter E. Changed serum trace element profile in Down?s syndrome. Biol Trace Elem Res 1996;54:201?6.

    35. Neve J, Sinet PM, Molle L, Nicole A. Selenium, zinc and copper in Down?s syndrome (trisomy 21): blood levels and relations with glutathione peroxidase and superoxide dismutase. Clin Chim Acta 1983;133:209?14.

    36. Purice M, Maximilian C, Dumitriu I, Ioan D. Zinc and copper in plasma and erythrocytes of Down?s syndrome children. Endocrinologie 1988;26:113?7.

    37. Bruhl HH, Foni J, Lee YH, Madow A. Plasma concentrations of magnesium, lead, lithium, copper, and zinc in mentally retarded persons. Am J Ment Defic 1987;92:103?11.

    38. Anneren G, Johansson E, Lindh U. Trace element profiles in individual blood cells from patients with Down?s syndrome. Acta Paediatr Scand 1985;74:259?63.

    39. Stabile A, Pesaresi MA, Stabile AM, et al. Immunodeficiency and plasma zinc levels in children with Down?s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunol Immunopathol 1991;58:207?16.

    40. Anneren G, Gebre-Medhin M. Trace elements and transport proteins in serum of children with Down syndrome and of healthy siblings living in the same environment. Hum Nutr Clin Nutr 1987;41:291?9.

    41. Antila E, Nordberg UR, Syvaoja EL, Westermarck T. Selenium therapy in Down syndrome (DS): a theory and a clinical trial. Adv Exp Med Biol 1990;264:183?6.

    42. Stabile A, Pesaresi MA, Stabile AM, et al. Immunodeficiency and plasma zinc levels in children with Down?s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunol Immunopathol 1991;58:207?16.

    43. Licastro F, Chiricolo M, Mocchegiani E, et al. Oral zinc supplementation in Down?s syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J Intellect Disabil Res 1994;38:149?62.

    44. Franceschi C, Chiricolo M, Licastro F, et al. Oral zinc supplementation in Down?s syndrome: restoration of thymic endocrine activity and of some immune defects. J Ment Defic Res 1988;32:169?81.

    45. Lockitch G, Puterman M, Godolphin W, et al. Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc. J Pediatr 1989;114:781?7.

    46. Bucci I, Napolitano G, Giuliani C, et al. Zinc sulfate supplementation improves thyroid function in hypozincemic Down children. Biol Trace Elem Res 1999;67:257?68.

    47. Licastro F, Mocchegiani E, Zannotti M, et al. Zinc affects the metabolism of thyroid hormones in children with Down?s syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. Int J Neurosci 1992;65:259?68.

    48. Napolitano G, Palka G, Lio S, et al. Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome? Ann Genet 1990;33:9?15.

    49. Napolitano G, Palka G, Grimaldi S, et al. Growth delay in Down syndrome and zinc sulphate supplementation. Am J Med Genet Suppl 1990;7:63?5.

    50. De Falco FA, D?Angelo E, Grimaldi G, et al. Effect of the chronic treatment with L-acetylcarnitine in Down?s syndrome. Clin Ter 1994;144:123?7 [in Italian].

    51. Jovanovic SV, Clements D, MacLeod K. Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Radic Biol Med 1998;25:1044?8.

    52. Jovanovic SV, Clements D, MacLeod K. Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Radic Biol Med 1998;25:1044?8.

    53. Bras A, Monteiro C, Rueff J. Oxidative stress in trisomy 21. A possible role in cataractogenesis. Ophthalmic Paediatr Genet 1989;10:271?7.

    54. Pincheira J, Navarrete MH, de la Torre C, et al. Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Down?s syndrome. Clin Genet 1999;55:192?7.

    55. Bras A, Monteiro C, Rueff J. Oxidative stress in trisomy 21. A possible role in cataractogenesis. Ophthalmic Paediatr Genet 1989;10:271?7.

    56. Metcalfe T, Bowen DM, Muller DP. Vitamin E concentrations in human brain of patients with Alzheimer?s disease, fetuses with Down?s syndrome, centenarians, and controls. Neurochem Res 1989;14:1209?12.

    57. Roizen NJ, Amarose AP. Hematologic abnormalities in children with Down syndrome. Am J Med Genet 1993;46:510?2.

    58. David O, Fiorucci GC, Tosi MT, et al. Hematological studies in children with Down syndrome. Pediatr Hematol Oncol 1996;13:271?5.

    59. Ibarra B, Rivas F, Medina C, et al. Hematological and biochemical studies in children with Down syndrome. Ann Genet 1990;33:84?7.

    60. Hestnes A, Stovner LJ, Husoy O, et al. Hormonal and biochemical disturbances in Down?s syndrome. J Ment Defic Res 1991;35:179?93.

    61. Harrell RF, Capp RH, Davis DR, et al. Can nutritional supplements help mentally retarded children? An exploratory study. Proc Natl Acad Sci 1981;78:574?8.

    62. Smith GF, Spiker D, Peterson CP, et al. Use of megadoses of vitamins and minerals in Down?s syndrome. J Pediatr 1984;105:228?34.

    63. Bidder RT, Gray P, Newcombe RG, et al. The effects of multivitamins and minerals on children with Down syndrome. Dev Med Child Neurol 1989;31:532?7.

    64. Kleijnen J, Knipschild P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Biol Psychiatry 1991;29:931?41 [review].

    65. Teksen F, Sayli BS, Aydin A, et al. Antioxidative metabolism in Down syndrome. Biol Trace Elem Res 1998;63:123?7.

    66. Kadrabova J, Madaric A, Sustrova M, Ginter E. Changed serum trace element profile in Down?s syndrome. Biol Trace Elem Res 1996;54:201?6.

    67. Neve J, Sinet PM, Molle L, Nicole A. Selenium, zinc and copper in Down?s syndrome (trisomy 21): blood levels and relations with glutathione peroxidase and superoxide dismutase. Clin Chim Acta 1983;133:209?14.

    68. Purice M, Maximilian C, Dumitriu I, Ioan D. Zinc and copper in plasma and erythrocytes of Down?s syndrome children. Endocrinologie 1988;26:113?7.

    69. Bruhl HH, Foni J, Lee YH, Madow A. Plasma concentrations of magnesium, lead, lithium, copper, and zinc in mentally retarded persons. Am J Ment Defic 1987;92:103?11.

    70. Anneren G, Johansson E, Lindh U. Trace element profiles in individual blood cells from patients with Down?s syndrome. Acta Paediatr Scand 1985;74:259?63.

    71. Stabile A, Pesaresi MA, Stabile AM, et al. Immunodeficiency and plasma zinc levels in children with Down?s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunol Immunopathol 1991;58:207?16.

    72. Anneren G, Gebre-Medhin M. Trace elements and transport proteins in serum of children with Down syndrome and of healthy siblings living in the same environment. Hum Nutr Clin Nutr 1987;41:291?9.

    73. Antila E, Nordberg UR, Syvaoja EL, Westermarck T. Selenium therapy in Down syndrome (DS): a theory and a clinical trial. Adv Exp Med Biol 1990;264:183?6.

    74. Stabile A, Pesaresi MA, Stabile AM, et al. Immunodeficiency and plasma zinc levels in children with Down?s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunol Immunopathol 1991;58:207?16.

    75. Licastro F, Chiricolo M, Mocchegiani E, et al. Oral zinc supplementation in Down?s syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. J Intellect Disabil Res 1994;38:149?62.

    76. Franceschi C, Chiricolo M, Licastro F, et al. Oral zinc supplementation in Down?s syndrome: restoration of thymic endocrine activity and of some immune defects. J Ment Defic Res 1988;32:169?81.

    77. Lockitch G, Puterman M, Godolphin W, et al. Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc. J Pediatr 1989;114:781?7.

    78. Bucci I, Napolitano G, Giuliani C, et al. Zinc sulfate supplementation improves thyroid function in hypozincemic Down children. Biol Trace Elem Res 1999;67:257?68.

    79. Licastro F, Mocchegiani E, Zannotti M, et al. Zinc affects the metabolism of thyroid hormones in children with Down?s syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. Int J Neurosci 1992;65:259?68.

    80. Napolitano G, Palka G, Lio S, et al. Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome? Ann Genet 1990;33:9?15.

    81. Napolitano G, Palka G, Grimaldi S, et al. Growth delay in Down syndrome and zinc sulphate supplementation. Am J Med Genet Suppl 1990;7:63?5.

    82. Roizen NJ, Amarose AP. Hematologic abnormalities in children with Down syndrome. Am J Med Genet 1993;46:510?2.

    83. David O, Fiorucci GC, Tosi MT, et al. Hematological studies in children with Down syndrome. Pediatr Hematol Oncol 1996;13:271?5.

    84. Ibarra B, Rivas F, Medina C, et al. Hematological and biochemical studies in children with Down syndrome. Ann Genet 1990;33:84?7.

    85. Hestnes A, Stovner LJ, Husoy O, et al. Hormonal and biochemical disturbances in Down?s syndrome. J Ment Defic Res 1991;35:179?93.

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