Ford C.; Moore A.J.; Jordan P.A.; Bartlett W.A.; Wyldes M.P.; Jones A.F.; MacKenzie W.E.
Dr. C. Ford, Department Clinical Biochemistry, Birmingham Heartlands Hospital, Bordesley Green, Birmingham B9 5ST United Kingdom
British Journal of Obstetrics and Gynaecology (United Kingdom), 1998, 105/8 (855-859)

Objective: To assess the utility of biochemical antenatal screening for Down's syndrome in a socioeconomically deprived area with a high proportion of Asian women from the Indian Subcontinent.

Design: Audit of Down's syndrome biochemical screening service over a four-year period.

Setting: Teaching hospital and community antenatal clinic in inner city Birmingham.

Population: Women booked between October 1992, and December 1996.

Methods: Blood for screening was collected between 14 and 21 weeks gestation, alpha-fetoprotein and intact human chorionic gonadotrophin were measured in serum and the risk of Down's syndrome was calculated.

Main outcome measures: Uptakes of screening and amniocentesis, screen positive rate, odds of being affected given a positive result, miscarriages associated with amniocentesis offered following a high risk result, detection rate, number of Down's cases prevented and a cost analysis. Outcome measures were compared between Asians and Caucasians.

Results: Overall 11,974 women (71%) accepted serum screening. The screen positive rate was 8.3% in Asians and 5.0% in Caucasians. The uptake of amniocentesis in women following a high risk result was 54% overall (35% Asian, 67% Caucasian). Nineteen cases of Down's syndrome were identified, of which 13 occurred in women who opted for biochemical screening. The detection rate of the biochemical screening programme was 85% (11/13). Of these 11 cases, six (none of whom were Asian) elected to have an amniocentesis, of whom four thereafter had a termination.

Conclusion: In this study the public health benefits of screening for Down's syndrome in a socioeconomically deprived area with a high Asian population, were small.

Pagano G.; Korkina L.G.; Brunk U.T.; Chessa L.; Degan P.; Del Principe D. ; Kelly F.J.; Malorni W.; Pallardo F.; Pasquier C.; Scovassi I.; Zatterale A.; Franceschi C.
G. Pagano, Italian National Cancer Institute, Fondazione G, Pascale, I-80131 Naples Italy
Medical Hypotheses (United Kingdom), 1998, 51/3 (253-266)

In spite of very distinct genotypic assets, a number of congenital conditions include oxidative stress as a phenotypic hallmark. These disorders include Fanconi's anaemia, ataxia telangiectasia, xeroderma pigmentosum and Bloom's syndrome, as well as two frequent congenital conditions: Down's syndrome and cystic fibrosis. Cancer proneness is a clinical feature shared by these disorders, while other manifestations include early ageing, neurological symptoms or congenital malformations. The onset of oxidative stress has been related to excess formation, or defective detoxification, of reactive oxygen species (ROS). This can arise from either the abnormal expression or inducibility of ROS-detoxifying enzymes, or by defective absorption of nutrient antioxidants. Resulting oxidative injury has been characterized through: (i) DNA, protein or lipid oxidative damage; (ii) excess ROS formation (in vitro and ex vivo); (iii) sensitivity to oxygen-related toxicity; (iv) improvement of cellular defects by either hypoxia or antioxidants; and (v) circumstantial evidence for in vivo oxidative stress (as e.g. clastogenic factors). Investigations conducted so far have been confined to individual disorders. Comparative studies of selected indicators for oxidative stress could provide further insights into the pathogenesis of each individual condition. Such a unified approach may have wide-ranging consequences for studies of ageing and cancer.

Manning C.A.; Honn V.J.; Stone W.S.; Jane J.S.; Gold P.E.
C.A. Manning, Department of Neurology, Box 394, Univ. of Virginia Hlth. Sci. Center, Charlottesville, VA 22908 United States
Neuropsychology (United States), 1998, 12/3 (479-484)

Glucose enhances memory in a variety of individuals, including people with Alzheimer's disease. By 35 years of age, adults with Down's syndrome (DS) develop the characteristic plaques and tangles found in Alzheimer's disease, despite findings indicating that not all older DS individuals meet criteria for dementia. To examine the possibility that glucose enhances memory in adults with DS (mean age = 35 years, range = 19-55 years), adults with DS were given a battery of tests specifically designed for individuals with DS in glucose and control conditions. No participant met criteria for dementia, regardless of age. Glucose enhanced performance on tests requiring both long-term memory and auditory processing. In addition, increased age was associated with poorer performance on the majority of tests in the control condition, indicating that cognitive decline with aging may be more prevalent in DS than previously believed.

Hsu J.J.; Hsieh T.T.; Soong Y.K.; Kuo B.
Dr. J.J. Hsu, Department Obstetrics and Gynecology, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei Taiwan
Journal of Maternal-Fetal Investigation (United States), 1998, 8/2 (66-70)

Objective: To investigate the relationship between maternal weight and serum alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (beta-hCG) levels and to determine the methodology of correction formulas for influencing the results of Down syndrome screening in an Asian population.

Methods: 8194 normal singleton pregnancies without any congenital anomalies were screened using AFP and free beta-hCG between 14 and 22 weeks of gestation. Down syndrome risk was calculated by bivariate gaussian algorithm that combined information from the two biochemical measurements and maternal age. The all points regression method and median regression method were used to approach the study cases. Linear and quadratic regression correction formulas for AFP and free beta-hCG, either in analyte multiples of the median (MoM) or log analyte MoM, against maternal weight have been proposed in this study.

Results: The mean maternal weight is 54.95 plus or minus 7.36 kg in Taiwanese pregnant women during the second trimester. There is a distinctly inverse relationship between maternal weight and serum marker levels. The log quadratic regression correction formula was the most satisfactory equation fit to the distribution of both AFP and free beta-hCG levels with a wide weight range. Routine weight correction may have the small benefit of reducing the screen-positive rate 0.36% at the risk cut-off level of 1:270.

Conclusions: Maternal weight may affect the AFP and free beta-hCG levels. Although there is no discernible effect in maternal weight adjustment, it is worth making weight corrections for serum marker levels in order to reduce individual variance.

Verma L.; Macdonald F.; Leedham P.; McConachie M.; Dhanjal S.; Hulten M.
Prof. M. Hulten, Molecular Medicine Research Centre, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL United Kingdom
Lancet (United Kingdom), 1998, 352/9121 (9-12)

Background. Prenatal diagnosis of chromosomal abnormality requires cytogenetic analysis of amniotic fetal cells. The necessary culture time delays diagnosis, is expensive, and requires substantial scientific expertise. In a masked prospective study, we investigated the feasibility of PCR amplification of chromosome 21 markers for the prenatal diagnosis of Down's syndrome.

Methods. The study population consisted of 2167 pregnant women, undergoing amniocentesis for prenatal diagnosis. In this cohort at least 1.5 mL amniotic fluid was available surplus to the requirements for traditional diagnostic methods. DNA was extracted from the surplus amniotic fluid and amplified in fluorescence-based PCR reactions, with three small-tandem-repeat markers located on chromosome 21. The products of the reactions were analysed on a DNA sequencer to identify the presence of two or three copies of chromosome 21.

Findings. In 2083 (97.4%) of 2139 samples of amniotic fluid that were not macroscopically blood-stained, two DNA markers gave an informative and correct result, identifying 2053 fetuses as normal and 30 as having trisomy 21 Down's syndrome (as confirmed by cytogenetic analysis). An extra marker was informative in 32 of 41 other clear samples. Thus a total of 99.6% informative results was achieved with these three markers. Macroscopically bloodstained samples (28 [1.3%]) were unsuitable for DNA testing. They gave a typical but non-informative result. There were no false-positive or false-negative results. Interpretation. The PCR-based DNA diagnostic test has great potential for improved prenatal diagnosis of Down's syndrome, with the advantage that results may be available within a day.

Finette BA; Rood B; Poseno T; Vacek P; Pueschel S; Homans AC
Department of Pediatrics, University of Vermont, Burlington 05401, USA.
Mutat Res (Netherlands) Jul 17 1998, 403 (1-2) p35-43

People with Down syndrome are 10-30 fold more likely to develop leukemia than the normal population. To date, little is known regarding the molecular mechanisms underlying this phenomenon. We have previously demonstrated that the spontaneous somatic mutant frequency (Mf) at a reporter gene, hypoxanthine-guanine phosphoribosyl transferase (HPRT), from a normal population showed a strict age dependency with an exponential increase in Mf from birth to late adolescents with a subsequent linear 2-5% increase per year in adults. In this study, we compared HPRT Mf in children and adults with Down syndrome using the HPRT T-cell cloning assay. We determined the Mf at the HPRT locus in 27 subjects with Down syndrome from ages 6 months to 53.4 years. Results demonstrated that background somatic Mf at the HPRT locus in children and adults with Down syndrome are not dependent on age as seen in a normal control population. Results also show that adults with Down syndrome have a significantly lower Mf than normal adults, and that children with Down syndrome have a significantly higher Mf than normal children, although the latter appears to be due to a decreased cloning efficiency (CE). These observations demonstrate that the frequency of spontaneous somatic mutations in children and adults with Down syndrome are atypical compared to normal controls, and suggest that the genetic mechanisms associated with background somatic mutational events in children and adults with Down syndrome may be different.

Shen JJ; Sherman SL; Hassold TJ
Department of Genetics and the Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Chromosoma (Germany) Jun 1998, 107 (3) p166-72

In species with chiasmate meioses, alterations in genetic recombination are an important correlate of nondisjunction. In general, these alterations fall into one of two categories: either homologous chromosomes fail to pair and/or recombine at meiosis I, or they are united by chiasmata that are suboptimally positioned. Recent studies of human nondisjunction suggest that these relationships apply to our species as well. However, methodological limitations in human genetic mapping have made it difficult to determine whether the important determinant(s) in human nondisjunction is absent recombination, altered recombination, or both. In the present report, we describe somatic cell hybrid studies of chromosome 21 nondisjunction aimed at overcoming this limitation. By using hybrids to "capture" individual chromosomes 21 of the proband and parent of origin of trisomy, it is possible to identify complementary recombinant meiotic products, and thereby to uncover crossovers that cannot be detected by conventional mapping methods. In the present report, we summarize studies of 23 cases. Our results indicate that recombination in proximal 21q is infrequent in trisomy-generating meioses and that, in a proportion of the meioses, recombination does not occur anywhere on 21q. Thus, our observations indicate that failure to recombine is responsible for a proportion of trisomy 21 cases.

Savage AR; Petersen MB; Pettay D; Taft L; Allran K; Freeman SB; Karadima G; Avramopoulos D; Torfs C; Mikkelsen M; Hassold TJ; Sherman SL
Department of Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hum Mol Genet (England) Aug 1998, 7 (8) p1221-7

Paternal non-disjunction of chromosome 21 accounts for 5-10% of Down syndrome cases, therefore, relative to the maternally derived cases, little is known about paternally derived trisomy 21. We present the first analysis of recombination and non-disjunction for a large paternally derived population of free trisomy 21 conceptuses ( n = 67). Unlike maternal cases where the ratio of meiosis I (MI) to meiosis II (MII) errors is 3:1, a near 1:1 ratio exists among paternal cases, with a slight excess of MII errors. We found no paternal age effect for the overall population nor when classifying cases according to stage of non-disjunction error. Among 22 MI cases, only five had an observable recombinant event. This differs significantly from the 11 expected events ( P < 0.02, Fisher's exact), suggesting reduced recombination along the non-disjoined chromosomes 21 involved in paternal MI non-disjunction. No difference in recombination was detected among 27 paternal MII cases as compared with controls. However, cases exhibited a slight increase in the frequency of proximal and medial exchange when compared with controls (0.37 versus 0.28, respectively). Lastly, this study confirmed previous reports of excess male probands among paternally derived trisomy 21 cases. However, we report evidence suggesting an MII stage-specific sex ratio disturbance where 2.5 male probands were found for each female proband. Classification of MII cases based on the position of the exchange event suggested that the proband sex ratio disturbance was restricted to non-telomeric exchange cases. Based on these findings, we propose new models to explain the association between paternally derived trisomy 21 and excessive male probands.

Witts P; Elders S
S. Tees Community and Mental Health NHS Trust, Normanby, Middlesbrough, UK.
Br J Clin Psychol (England) May 1998, 37 ( Pt 2) p213-6

OBJECTIVES: To examine the utility of the 'Severe Impairment Battery' (SIB--Thames Valley Test Company) in assessing cognitive ability of adults with Down syndrome .

DESIGN: A within-subject repeated measures design was used to determine test-retest reliability of the SIB and the Vineland Adaptive Behaviour Scales (Interview Edition--Survey Form, 1984) were used to establish SIB criterion validity.

METHODS: Thirty-three adults with Down syndrome (from 152 known to an NHS Trust learning disability service) were selected on the basis of their or their carers' written consent. At the first administration of the SIB with the participant, a staff member completed a Vineland ABS. Thirty days later, the SIB was readministered to the participant.

RESULTS: Test-retest reliability of the SIB was high as was criterion validity determined by correlating SIB and Vineland ABS scores. Floor effects were not encountered.

CONCLUSIONS: The SIB can successfully be used with adults with Down syndrome to assess cognitive functioning over a wide range of ability and may be useful, if used longitudinally, in assessing for deterioration in cognitive functioning associated with dementia. Methodological limitations are discussed.

Bischoff FZ; Lewis DE; Nguyen DD; Murrell S; Schober W; Scott J; Simpson JL; Elias S
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Am J Obstet Gynecol (United States) Jul 1998, 179 (1) p203-9

OBJECTIVE: Currently, prenatal diagnosis of chromosome abnormalities requires invasive techniques such as amniocentesis and chorionic villus sampling that carry small but finite risks of fetal loss. A noninvasive approach is to isolate fetal cells from maternal blood by flow sorting followed by genetic interphase analysis with fluorescence in situ hybridization. Because the ratio of fetal to maternal cells is relatively low after flow sorting and to detect 90% to 95% of fetal aneuploidies associated with serious birth defects, a 5-color fluorescent in situ hybridization strategy is necessary for simultaneous detection of chromosomes X, Y, 13, 18, and 21 in all flow-sorted nuclei recovered from a specimen.

STUDY DESIGN: Fetal nucleated red blood cells were isolated from maternal blood in 40 cases (10.4 to 27.0 weeks' gestation) by flow cytometry on the basis of positive selection of CD71+ (transferrin receptor), CD45-, and LDS751 staining. Each case was evaluated for 5-color fluorescent in situ hybridization efficiency by determining the percentage of flow-sorted nuclei containing 8 hybridization signals for chromosomes X, Y, 13, 18, and 21.

RESULTS: A total of 42,312 flow-sorted nuclei from maternal blood samples were analyzed. In 5 of 16 (31%) cases with a male fetus, 0.16% of nuclei scored were identified as fetal by the presence of 1 signal each for chromosomes X and Y. Fetal trisomy 21 nuclei were accurately detected in 2 cases with a female fetus, each of which was subsequently confirmed.

CONCLUSIONS: Five-color interphase fluorescent in situ hybridization analysis can be used to effectively analyze rare fetal aneuploid nuclei in enriched flow-sorted cells isolated from maternal blood.

Dumaret AC; De Vigan C; Julian-Reynier C; Goujard J; Rosset D; Ayme S
CERMES-INSERM U.304, Paris, France.
Prenat Diagn (England) May 1998, 18 (5) p437-45

Recently, professionals in France have noticed an increase in newborns with Down syndrome (DS) being placed for adoption. The aim of this study was to investigate DS babies given up at birth for adoption and to consider the possible determinants of this in order to assess social acceptance of DS. A retrospective cohort of all living DS babies was collected from two birth-defect registries (Paris: 1981-1990; Marseilles area: 1984-1990). Follow-up data were collected: characteristics of the baby, biological parents and maternity units, age when given up for adoption, and type of foster care. The results showed that 19.4 per cent of infants with DS (115/593) were rejected by their parents. Multiple regression analysis indicated that foreign origin of the mother, area of residence, no associated major malformation, maternal age (15-24 years), and birth rank (> 2) variables were significantly associated with a lower placement rate. Among the 115 abandoned infants with DS, 88 came from unknown parentage (76.5 per cent). For half of them, adoptive placement (88/115) occurred before the age of 6 months. Socio-cultural attitudes play a great part in these family decisions. Equally important is the manner in which professionals propose adoption as an alternative to these parents of DS babies. They should be encouraged to consider all options before making a decision, so that the best solution can be found for the interest of all.

Bahado-Singh RO; Oz U; Kovanci E; Cermik D; Flores D; Copel J; Mahoney M; Cole L
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
J Matern Fetal Med (United States) May-Jun 1998, 7 (3) p111-4

In this study we report a new triple test that combines serum AFP, urine beta-core fragment of hCG, total urine estriol, and maternal age for calculating individual Down syndrome odds in the second trimester. The urine beta-core fragment/estriol ratio was used as a single screening variable. Analyte levels were measured prospectively in 10 Down syndrome cases and 346 normals. Individual Down syndrome odds were calculated by multiplying the product of the Down syndrome likelihood ratios of serum AFP and urine beta-core/estriol levels by the age-related midtrimester risk. The screening efficiency of an algorithm that combines urine beta-core/estriol with maternal age was compared to one that included serum AFP data. A 90% detection rate for Down syndrome was obtained at a 4.65% false positive rate. This was superior to the 75% sensitivity at 5% false positive rate observed when beta-core/estriol and age alone were used. This new triple test has a higher screening efficiency than that generally reported for the traditional serum triple screen and other urine tests, and it also provides information on the risk of neural tube defects. If confirmed in larger trials, the new algorithm could be used as an alternative to the traditional serum triple screen.

Evidence against the involvement of reactive oxygen species in the pathogenesis of neuronal death in Down's syndrome and Alzheimer's disease

Hayn M.; Kremser K.; Singewald N.; Cairns N.; Nemethova M.; Lubec B.; Lubec G.
Department of Pediatrics, University of Vienna, Wahringer-Gurtel 18-20, A-1090 Vienna Austria
Life Sciences (USA), 1996, 59/7 (537-544)

It has been proposed that the pathogenesis of Down's Syndrome (DS) involves reactive oxygen species (ROS) arising from a gene dosage effect that disproportionately elevates superoxide dismutase (SOD1) activity. It was also suggested that generation of ROS might be responsible for neuronal death in Alzheimer's Disease (AD). Little data on brain ROS in DS and AD exist; therefore, we determined activities of choline acetyltransferase (CHAT) and of the oxidative defense enzymes SOD1 and glutathione peroxidase (GSHPx) in frontal cortex of aged patients with DS and AD. We also measured levels of malondialdehyde, which reflects lipid peroxidation, and o- tyrosine, which represents the hydroxyl radical attack. ChAT was significantly reduced in cortex of patients with DS (-68%) and AD (-66%) as compared to controls. There were no statistically significant differences, however, between controls and both neurodegenerative disorders for SOD1, GSHPx, malondialdehyde and o-tyrosine. Our data contradict the only previous finding on increased SOD1 and ROS in brains of patients with DS: age as well as methodological differences might account for the discrepancy. In conclusion, no evidence for a pathogenetic role of SOD1, GSHPx, lipid peroxidation or hydroxyl radical attack in aged patients with DS and AD could be provided.

Sequence of deposition of heterogeneous amyloid beta-peptides of APO E in Down syndrome: Implications for initial events in amyloid plaque formation

Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Neurobiol Dis 1996 Feb;3(1):16-32

Patients with trisomy 21 (Down syndrome (DS)) progressively develop amyloid beta-protein (Abeta) deposits and then other features of Alzheimer's disease (AD) apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein. Because the neuropathological phenotype in older DS subjects closely resembles that of AD, the examination of DS brains of increasing age provides a unique model of the progression of AD. Here, we characterized the deposition of several Abeta peptides and apolipoprotein E in formalin-fixed brain sections from 29 DS subjects between 3 and 73 years old. Amyloid plaque number and the percentage of cortical area they occupied were quantified by computerized image analysis. Abeta ending at amino acid 42 (Abeta42) was the earliest form of Abeta deposited in DS cortex. It was observed in 7 of 16 young (3-30 years) subjects, with the earliest deposition occurring at age 12. Abeta ending at residue 40 (Abeta40) was not detected until similarage 30, a time when degenerating neurites around Abeta immunoreactive (IR) plaques were first observed, and the frequency of Abeta40 IR plaques then rose with age. Even in old (51-73 years) DS subjects, Abeta42 IR plaques were always more abundant than Abeta40 IR plaques. Abeta peptides starting at aspartate 1 or pyroglutamate 3 were detected in small subsets of compacted, neuritic plaques beginning around age 30 and rose with age, the latter species always exceeding the former. Thus, the N-termini of the Abeta42 peptides abundantly deposited in very young DS subjects remain unknown. Apo E was detectable in a small subset of Abeta42 IR plaques beginning at age 12 and rose steadily with age; it clearly followed the deposition of Abeta. Our analysis of very young DS brains suggests that amyloid plaque formation begins with Abeta42-ending peptides, and the number and percentage of cortical area of Abeta42 plaques increase very little with advancing age, while other heterogeneous Abeta species and Apo E progressively accrue onto plaques containing Abeta42.

Vitamin E and Alzheimer's disease in subjects with Down's syndrome.

Jackson, C. V.; Holland, A. J.; Williams, C. A.; Dickerson, J. W.
U Surrey Div of Nutrition & Food Science, Guildford, England
Journal of Mental Deficiency Research 1988 Dec Vol 32(6) 479-484

Tested the hypothesis that a low level of serum Vitamin E would be associated with a likelihood of dementia in 24 Ss (aged 30+ yrs) with Down's syndrome. Blood samples were drawn, and evidence of deterioration in self-care skills was assessed. Nine Ss showed evidence of Alzheimer's disease (AD), and 9 did not. Plasma Vitamin E levels measured in Ss with AD were lower than in Ss without AD. It is suggested that there may be an interaction between risk of AD and the protective action of Vitamin E.

Behavioral disorders, learning disabilities and megavitamin therapy.

LaPerchia, Phyllis
New York City Board of Education, NY, US
Adolescence 1987 Fal Vol 22(87) 729-738

Reviews research on megavitamin nutritional therapy for learning disabilities in general, schizophrenia, autism, mental retardation and Down's syndrome, and hyperkinesis. Methodological problems in the studies are noted, and a holistic approach to treating the learning and behaviorally disabled is advocated.

Hambidge, D. M.
Princess Alexandra Hosp, Swindon, England
British Journal of Psychiatry 1986 Dec Vol 149 797-798

Questions R. L. Welfare and K. E. Hewitt's (see PA, Vol 74:22330) proposal of a causal relationship between cognitive decline and macrocytosis in Down's syndrome, suggesting that both may be related to undetected folate vitamin deficiency.

Foreman, Philip J.; Ward, James
Newcastle Coll of Advanced Education, Australia
Australia & New Zealand Journal of Developmental Disabilities

Reviews research into treatment approaches in Down's syndrome, including pharmacological therapy (e.g., thyroid treatment, 5-hydroxytryptophan (5-HTP), vitamin and mineral therapy, cell therapy), the G. Doman (1974) program of movement patterning, early intervention, and facial plastic surgery.

A double blind study of vitamin B-sub-6 in Down's syndrome infants: I. Clinical and biochemical results.

Coleman, Mary et al
Georgetown U School of Medicine
Journal of Mental Deficiency Research 1985 Sep Vol 29(3) 233-240

19 infants with Down's syndrome participated in a double-blind study of the clinical effects of pharmacological doses of vitamin B-sub-6 administration, starting under 8 wks of age and continuing until 3 yrs of age. 10 Ss received the vitamin and 9 the placebo. No statistically significant differences were found between the 2 groups in mental age, height, weight, cranial circumference, or tongue protrusion. Vitamin B-sub-6 significantly elevated whole blood 5-hydroxytryptamine during the 1st yr. A study of side effects conducted on a larger open population of 400 Down's syndrome patients (from infants to aged 12 yrs) found vitamin B-sub-6 to be relatively safe when administered over long periods of time, with photosensitive blisters as the major complication.

A double blind study of vitamin B-sub-6 in Down's syndrome infants: II. Cortical auditory evoked potentials.

Frager, Joseph; Barnet, Ann; Weiss, Ira; Coleman, Mary
Montefiore Hosp & Medical Ctr, Dept of Medicine, New York, NY
Journal of Mental Deficiency Research 1985 Sep Vol 29(3) 241-246

Recorded cortical auditory evoked potentials (CAEPs) at 1 and at 3 yrs of age in 19 children with Down's syndrome participating in a double-blind trial of vitamin B-sub-6 and placebo that was begun in early infancy and continued for 3 yrs. CAEPs have previously been shown to have abnormally high amplitude in Down's syndrome patients. The CAEPs of the Ss in the B-sub-6-treated and placebo groups were compared. Only minor effects were found in the CAEPs recorded at 1 yr of age. At 3 yrs of age, however, comparison of the B-sub-6-treated group and the placebo group revealed significant differences in both amplitudes and latencies of CAEP components. Peak-to-peak amplitudes of prominent components were significantly lower in B-sub-6-treated Ss than in their placebo controls. Amplitude correlated in some cases with whole blood serotonin levels. Latencies for several prominent evoked peaks were significantly longer in B-sub-6-treated Ss. Findings suggest a difference in neurodevelopmental trajectories that seems to be a pharmacological effect of B-sub-6 administration. (17 ref)

Xylose absorption in Down's syndrome.

Williams, Celia A. et al
U Surrey, Div of Nutrition & Food Science, Guildford, England
Journal of Mental Deficiency Research 1985 Jun Vol 29(2) 173-177

Conducted a standard xylose absorption test in 14 25-61 yr old Ss with Down's syndrome (DS) and in 14 sex- and age-matched mentally retarded controls; another 30 14-57 yr olds with DS were similarly investigated. Mentally retarded Ss as a group had impaired xylose absorption, and the matched DS Ss had a significantly reduced xylose absorption when compared to the mentally retarded controls. It is suggested that the malabsorption plays a role in a number of the vitamin and mineral deficiencies found in people with DS.

Nutritional aspects of Down's syndrome with special reference to the nervous system.

Sylvester, Peter E.
St Lawrence's Hosp, Caterham, England
British Journal of Psychiatry 1984 Aug Vol 145 115-120

Reviews studies that demonstrate that patients with Down's syndrome (DS) are prone to suffer multiple deficiencies of vitamins and lifelong shortages of some trace metals. A significant reason for these deficiencies is malabsorption from the intestine. Reversal and control by treatment of vitamin deficiencies have been reported. The brain in DS does not develop adequately; one area, the hippocampus, which is concerned with memory, is poorly developed. A major neuropathological feature of DS is premature aging of the Alzheimer type. The incidence of aging based on pathological findings is demonstrated and compared with senile changes in adults with DS. The role of nutrients is discussed in relation to damage to the mature brain and to the aging process.

Children's mental retardation study is attacked: A closer look.

Schauss, Alexander G.; Sommars, Elisabeth
American Inst for Biosocial Research, Tacoma, WA
International Journal of Biosocial Research 1982 Vol 3(2) 75-86

Discusses research done to determine whether nutritional supplements can help mentally retarded children. The research has come under the attack from the Committee on Nutrition of the American Academy of Pediatrics (AAP). R. F. Harrell (1981) reported that when her team took 22 developmentally disabled children and placed them on vitamin supplements called the G-T-C formula in a double-blind, crossover study during an 8-mo period, they were able to consistently cause a significant increase in all the Ss' IQs. Two ongoing studies in the area of mental retardation and nutritional supplements are discussed in an effort to determine attempts to corroborate Harrell's findings. In the 1st study, 60 Down's Syndrome schoolchildren (aged 7-14 yrs) are involved in a 6-mo preexamination stage in which they are undergoing a series of tests, including tests to detect thyroid problems. These tests have been chosen to disprove a criticism by the AAP that suggested improvement in the Harrell children may have been due to a correction in thyroid problem. In the 2nd study, 40 children with Down's Syndrome are being tested, with half the Ss receiving the G-T-C formula and the other half receiving placebos. It is concluded that there is much hope for children with developmental disabilities in nutritional studies that examine the possibility of brain regeneration.

Effects of nutritional supplementation on IQ and certain other variables associated with Down syndrome.

Weathers, Caislin
Georgia Mental Health Inst, Atlanta
American Journal of Mental Deficiency 1983 Sep Vol 88(2) 214-217

In a double-blind study, 24 6-17 yr old Down's syndrome children (Iqs 30-67 at the start of the study) who were living at home were given a megadose multivitamin/mineral supplement for 4 mo. A matched group of 23 children received a placebo in identical form. Ss' IQ (Stanford-Binet Intelligence Scale), vision, and visual-motor integration (Beery-Buktenica Developmental Form Sequence) were tested before and after supplementation, and weekly checks were made to monitor behavioral changes. No differences were found on any measures as a result of supplementation. (10 ref)

Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome.

Barden, H. S.
U Illinois
Journal of Mental Deficiency Research 1977 Mar Vol 21(1) 63-74

Assessed vitamin A and carotene values of 44 3-34 yr old Down's syndrome, 56 3-35 yr old non-Down's syndrome mentally retarded, and 40 normal 1-25 yr old Ss. Dietary and environmental uniformity was maintained by utilizing Down's and non-Down's Ss residing in the same institution. Results show that Down's Ss showed vitamin A values that were significantly higher than those of the non-Down's retarded Ss and similar to those of the normal Ss. Carotene values were similar in the Down's and non-Down's retarded groups, but were significantly higher than those of the normal Ss. This difference in carotene is seen as reflecting in part the high level of carotenoid products in the institutional diet. Carotene/vitamin A ratio values are reported, and the possibility that relatively high ratio values reflected a decreased efficiency in converting carotene to vitamin A is discussed. It is suggested that Down's Ss may suffer some impairment in the utilization of vitamin A at its site of action.

Sodium-dependent glutamate binding in senile dementia.

McGeer, Edith G.; Singh, Edith A.; McGeer, Patrick L.
U British Columbia, Kinsmen Lab of Neurological Research, Vancouver, Canada
Neurobiology of Aging 1987 May-Jun Vol 8(3) 219-223

Investigated sodium-dependent glutamate binding as a possible index of the integrity of glutamate/aspartate nerve endings in 7 cortical areas from postmortem brains of 15 persons with senile dementia of the Alzheimer type (SD); 10 controls matched for age, sex, and postmortem delay (PMD); and single cases of Down's syndrome and Parkinson-dementia. Results show that binding affinities were variable from brain to brain. Specific binding site densities showed overall a significant negative correlation with PMD, a significant decrease in SD, and a significant correlation in the SD samples with choline acetyltransferase activities.

Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue.

Godridge, H.; Reynolds, G. P.; Czudek, C.; Calcutt, N. A. et al
U Nottingham Medical School, Queen's Medical Ctr, England
Journal of Neurology, Neurosurgery & Psychiatry 1987 Jun Vol 50(6) 775-778

Analyzed brain tissue taken at necropsy from 5 cases of Down syndrome and 6 controls for changes in neurotransmitter markers. Concentrations of noradrenaline (NA), dopamine and its major metabolite homovanillic acid, and 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid were determined by high pressure liquid chromatography, while choline acetyltransferase (ChAT) was measured by a radiochemical technique. Significant reductions in NA, 5-HT and ChAT were found in most cortical and subcortical regions of the Down syndrome tissue. Neuropathological lesions were also assessed. Results indicate profound transmitter deficits and neuropathological abnormalities in adult patients with Down syndrome that closely resemble those of Alzheimer's disease.

A report on phosphatidylcholine therapy in a Down Syndrome child.

Cantor, David S.; Thatcher, Robert W.; Ozand, Pinar; Kumin, Libby et al
U Maryland School of Medicine, Applied Neuroscience Research Inst, Baltimore
Psychological Reports 1986 Feb Vol 58(1) 207-217

Presents the case of a 21/2-yr-old Downs syndrome (DS) boy who was given a phosphatidylcholine supplement (150 mg/kg, day) over a 7-mo period. Measures of the EEG indicate a normalization during the treatment period with minor reoccurrence of abnormalities during a placebo period. S showed a definitive increase in speech and language skills as well as general motor skills that exceeded same-aged DS peers experiencing like training programs. Data suggest that phosphatidylcholine therapy may be useful for improving neurophysiological and intellectual functioning of some DS children.