Acta Paediatr: 96 (10): 1479-82 (2007 Oct)

Immunological patterns in young children with Down syndrome: is there a temporal trend?

Cocchi G; Mastrocola M; Capelli M; Bastelli A; Vitali F; Corvaglia L
Neonatology and Preventive Paediatric Department, University of Bologna, Bologna, Italy

Down syndrome is associated with an increased susceptibility to infections due to a deficiency of both specific and nonspecific immunity. Aim: The aim of the study was to analyze the temporal trends, if any, of some variables related to the immunological status of children affected by Down syndrome. Methods: Heparinized blood samples were obtained by venipuncture in 30 children with Down syndrome, who were regularly followed in our department and analyzed for hematologic values, lymphocyte subpopulations, immunoglobulin dosage and zinc level. Results were compared with those of the normal population. Results: In the first 5 years of life, we observed a progressive decrease in the medium values of lymphocytes, CD4+ and plasma zinc levels, and an increase in CD8+, immunoglobulin A, immunoglobulin G, immunoglobulin M and natural killer, but generally without exceeding the interval of normality. Conclusions: In Down syndrome children, the immune cellular status is similar to the normal population as far as white blood cell, lymphocyte, CD4+, CD8+, natural killer and immunoglobulins are concerned. Plasma level of zinc is normal from birth until 5 years but with a temporal trend of progressive reduction. This observation supports the hypothesis that a pharmacological supplementation may be necessary in Down syndrome children only after 5 years of age.
Invest Clin 44 (1): 51-60 (2003 Mar)

Diminished zinc plasma concentrations and alterations in the number of lymphocyte subpopulations in Down's syndrome patients

Soto-Quintana M, Alvarez-Nava F, Rojas-Atencio A, Granadillo V, Fernandez D, Ocando A, Lopez E, Fulcado W
Seccion de Citogenetica, Unidad de Genetica Medica, Facultad de Medicina, Universidad del Zulia, Hospital Universitario, Apartado Postal 15066, Maracaibo, Estado Zulia, Venezuela

Alterations of plasma levels of zinc and in the immune system in Down's syndrome (DS) have been reported. These alterations have been associated with a high rate of infectious diseases, which represent the main cause of mortality in affected individuals. The objectives of this study were to determine plasma zinc levels and to evaluate the immune system in DS patients. Peripheral blood samples were obtained from 43 DS patients examined at the Unidad de Genetica Medica, Universidad del Zulia in Maracaibo, Venezuela. Their mean age (± SD) was 2.3 ± 2.0 years. As control group, 40 healthy children were studied (mean ± SD 2.3 ± 2.0 years). Karyotypes by a standard technique, the determination of plasma levels of zinc by atomic absorption spectrophotometry and the evaluation of the immune system by flow cytometry were carried out in the study groups. All DS patients had free trisomy 21. Significantly disminished zinc plasma levels, helper T lymphocyte (CD4) percentage, helper/cytotoxic (CD4/CD8) ratio and B-cells (CD19) were found in DS patients by matching with control group. An increase in CD8 was also found. No significative difference in the lymphocyte subpopulations between DS patients with disminished plasma levels of zinc and DS patients with normal zinc were found. These findings suggest that zinc deficiency is not the sole etiology involved in the disorders of immune system seen in DS patients. Other factors, such as thymic alterations and molecular abnormalities due to gene overexpression of loci located on chromosome 21 could be involved. Although, zinc supplementation is recommended in these patients with zinc deficiency, further studies with a double-blind, placebo versus zinc design are needed to evaluate the potentially beneficial effects of zinc treatment in DS patients.
Biol Trace Elem Res 67 (3): 257-68 (1999 Mar)

Zinc Sulfate Supplementation Improves Thyroid Function in Hypozincemic Down Children

Bucci I, Napolitano G, Giuliani C, Lio S, Minnucci A, Di Giacomo F et al.
Cattedra di Endocrinologia, Universita G. D'Annunzio, Chieti, Italy

In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate (1) the role of zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in Down children cyclically supplemented with zinc sulfate. Inverse correlations have been observed between age and triiodotironine (T3) and between zinc and thyroid-stimulating hormone (TSH); higher TSH levels have been found in hypozincemic patients at the beginning of the study. After 6 mo of supplementation, an improvement of thyroid function (TSH levels: 3.96 ± 1.84 vs 2.64 ± 1.33 mUI/mL basally and after 6 mo, respectively) was observed in hypozincemic patients. In the second cycle of supplementation, a similar trend of TSH was observed. At the end of the study, TSH significantly decreased in treated hypozincemic subjects (4.48 ± 1.93 vs 2.96 ± 1.20 mUI/mL) and it was no longer different in comparison to normozincemic patients. We suggest zinc supplementation to the diet in hypozincemic Down children as a simple and useful therapeutic tool.
Ultrastruct Pathol 20 (5): 457-201 (1996 Sep)

Programmed cell death of peripheral myeloid precursor cells in Down patients: effect of zinc therapy

Trubiani O, Antonucci A, Palka G, Di Primio R

Hemopoietic stem cell differentiation represents the primary rule of self-renewal, proliferation, and specialization modulated by several mechanisms, including growth factors, cell interactions, and bioavailability of various ions, especially Ca2+ and Zn2+. Apoptotic death, during normal cell turnover, has been widely studied and is recognized as an important pathway for clonal deletion in the hemopoietic system. Multiparametric analyses have shown that subjects with Down syndrome show low levels of plasmic zinc associated with the presence of immature myeloid cells in the peripheral blood. This arrangement is repaired by in vivo zinc therapy. This study presents morphological and biochemical analyses to show that ZnSO4 therapy induces the disappearance of peripheral myeloid precursor cells by a programmed cell death mechanism. The programmed zinc-therapy-induced cell death presumably provides a simple way to regulate the myeloid differentiation selecting appropriate cells.
Biol Trace Elem Res 54 (3): 201-6 (1996 Sep)

Changed serum trace element profile in Down's syndrome

Kadrabova J, Madaric A, Sustrova M, Ginter E
Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic

Being cofactors of important antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), which are significantly modified in Down's syndrome (trisomy 21), serum levels of microtrace elements zinc, copper, and selenium and of macroelement magnesium are reported in 16 subjects with Down's syndrome (DS) and their respective well age- and sex-matched controls. Serum zinc and selenium levels were significantly lowered in DS subjects, whereas copper levels were elevated. Consequently, a marked increase (40%) of the copper/zinc ratio in DS persons was observed. There were no differences in serum levels of magnesium between DS and control subjects.
J Endocrinol Invest 17(6): 385-90 (1994 Jun)

Thyroid function and plasma immunoglobulins in subjects with Down's syndrome (DS) during ontogenesis and zinc therapy

Šustrová M; Strbak V
Department of Clinical Immunology, Children's Hospital, Bratislava, Slovakia

Thyroid function parameters and immunoglobulin concentrations in sera of outpatients with Down's syndrome (DS, n = 110) of different ages (DS1 = 1-9 years; DS2 = 6-15; DS3 = 15-35) were compared with those of age-matched controls (n = 110). Although mean serum TSH was higher in all DS groups, thyroid hormone concentrations were significantly lower only in DS3. In DS1, a notable frequency rate of high T4 and T3 was found. Serum concentrations of thyroxine binding globulin (TBG) were significantly higher in all DS groups. Free T4 and T3 indexes, calculated as the ratio of total hormone: TBG concentrations, were lower in all DS groups. IgA serum concentrations were significantly higher in all DS groups, IgA was higher in DS1 and DS2. Serum zinc levels were lower in all DS groups. Repeated examination after one year revealed lower T4 and higher TSH in DS patients treated with zinc during this interval as compared to values observed before treatment. Our results suggest a high occurrence rate of complex immune and endocrine disorders with thyroid dysregulation in DS patients, with zinc deficiency playing a considerable role.
J Trace Elem Electrolytes Health Dis 7 (4): 237-9 (1993 Dec)

Modulation of the neuroendocrine system and immune functions by zinc supplementation in children with Down's syndrome

Licastro F; Mocchegiani E; Masi M; Fabris N
Department of Experimental Pathology, University of Bologna, Italy

Plasma levels of TSH, T4, T3, and reversal T3 (rT3) were measured in 51 children with trisomy of the chromosome 21 and in 15 controls. Levels of TSH were higher in children with DS than in controls and rT3 levels were decreased. However, T3 and T4 levels were in the normal range. Plasmic zinc and thymulin, a zinc-dependent thymichormone, were also decreased. After dietary supplementation with ZnSO4, levels of plasmic zinc, thymulin, TSH and rT3 were restored. A follow up of DS children one year after the cessation of zinc therapy showed that plasma levels of zinc decreased and TSH lightly increased. Zinc deficiency may play a crucial role in the pathogenesis of thyroid gland disfunction which leads to the autoimmune hypothyroidism often observed in this syndrome.
Am J Med Genet Suppl 7: 63-5 (1990)

Growth delay in Down syndrome and zinc sulphate supplementation

Napolitano G; Palka G; Grimaldi S; Giuliani C; et al
Chair of Endocrinology, University G. D'Annunzio, Chieti, Italy

Children affected with Down syndrome (DS) show deficient growth, immunodeficiency—especially concerning the T-cell population—and low plasma zinc levels. New growth charts have been recently proposed, and zinc supplementation to the diet has been reported to improve transiently the efficiency of the immune system. 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 (16 males and 6 females) who received zinc sulphate for 6 to 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 average height velocity changed from 23.84 ± 7.98 mm/6 months to 40.80 ± 7.68 mm/6 months. Growth hormone serum level was 5.94 ± 4.89 ng/ml compared with 7.49 ± 6.75 ng/ml before and after therapy, respectively. Somatomedin serum level was 160.27 ± 68.88 mU/ml and 205 ± 124.07 mU/ml before and after therapy, respectively. In conclusion, zinc sulphate therapy of patients with DS affects not only the immune system, as previously reported, but can also accelerate growth.
Ann Genet 33 (1): 9-15 (1990)

Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome?

Napolitano G; Palka G; Lio S; Bucci I; De Remigis P Stuppia L; Monaco F
Chairs of Endocrinology, University G. d'Annunzio, Chieti, Italy

In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymicinvolution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism.