Contributions to Racial Disparity in Mortality among Children with Down Syndrome.

OBJECTIVE: To evaluate whether racial differences across a variety of medical factors collected in a longitudinal clinical database at a specialty clinical for children with Down syndrome provide insight into contributors to racial disparity in mortality. STUDY DESIGN: Comprehensive medical histories of 763 children receiving medical care at a Down syndrome specialty clinic were retrospectively reviewed regarding prenatal, postnatal, and medical issues, as well as subspecialty referrals. Frequency calculations and logistic regression were performed. The National Death Index was used to query death record databases to correlate medical histories with mortality data. RESULTS: Prenatal drug use and intubation were significantly more frequent, but hyperbilirubinemia was significantly less frequent, in black children compared with white children with Down syndrome. Among children with Down syndrome aged <5 years, significant increases in referral to cardiology were seen for black children compared with white children. Trends were seen in an increased incidence of congenital heart disease for black children. Correlations with death records did not demonstrate differences in rates of cardiac-related deaths. Minimal racial disparity was seen for all other measures investigated. CONCLUSION: Racial disparity in mortality exists, but the underlying cause remains unidentified despite use of a comprehensive, longitudinal database of individuals with Down syndrome and review of death records. Referrals to cardiology might be a clue to the underlying cause, perhaps as an indicator of access to care, but cardiac disease does not account for the disparity in mortality.

Difference in age at regression in children with autism with and without Down syndrome.

OBJECTIVE: Autism occurs more frequently in individuals with Down syndrome than it does in the general population. Among children with autism and Down syndrome, regression is reported to occur in up to 50%. The aim of this study was to characterize and compare regression in children with autism with and without Down syndrome. METHODS: In this case-control study, children with Down syndrome and autism characterized by a history of developmental regression (n = 12) were compared to children with autism with regression who did not have Down syndrome, matched for chronologic age and gender. Comparisons were made on age at acquisition of language and age at loss of language and other skills as measured by the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: The mean age at acquisition of meaningful use of single words was 40.6 months (SD = 38.0) in children with Down syndrome and autism compared to 14.9 months (SD = 8.5) in children with autism without Down syndrome (p = .005). The mean age at language loss in children with autism with Down syndrome was 61.8 months (SD = 22.9) compared to 19.7 months (SD = 5.8) for those with autism without Down syndrome (p = .01). The mean age at other skill loss was 46.2 months (SD = 19.1) and 19.5 months (SD = 5.6), respectively (p = .006). CONCLUSIONS: When regression occurs in children with autism and Down syndrome it is, on average, much later than is typically seen in children with autism without Down syndrome.

Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21.

Endogenous coenzyme Q10 is an essential cofactor in the mitochondrial respiratory chain, a potent antioxidant, and a potential biomarker for systemic oxidative status. Evidence of oxidative stress was reported in individuals with trisomy 21. In this study, 14 children with trisomy 21 had significantly increased (P < 0.0001) plasma ubiquinone-10 (the oxidized component of coenzyme Q10) compared with 12 age- and sex-matched healthy children (historical controls). Also, the mean ratio of ubiquinol-10 (the biochemically reduced component):total coenzyme Q10 was significantly decreased (P < 0.0001). After 3 months of ubiquinol-10 supplementation (10 mg/kg/day) to 10 patients with trisomy 21, the mean ubiquinol-10:total coenzyme Q10 ratio increased significantly (P < 0.0001) above baseline values, and 80% of individual ratios were within normal range. No significant or unexpected adverse effects were reported by participants. To our knowledge, this is the first study to indicate that the pro-oxidant state in plasma of children with trisomy 21, as assessed by ubiquinol-10:total coenzyme Q10 ratio, may be normalized with ubiquinol-10 supplementation. Further studies are needed to determine whether correction of this oxidant imbalance improves clinical outcomes of children with trisomy 21.

Coenzyme Q10 absorption and tolerance in children with Down syndrome: a dose-ranging trial.

Controlled studies of coenzyme Q(10) dosing and tolerance have been reported in adults, but not in pediatric patients. This study compares low- and high-dose coenzyme Q(10) (LiQ-NOL syrup) absorption and tolerance in children with Down syndrome. After a 1-month low-dose (1.0 mg/kg/day) run-in period, all participants received high-dose coenzyme Q(10) (10.0 mg/kg/day) for two additional months (in randomized sequence as one daily dose or split into two daily doses). Chemistry profiles and complete blood counts were determined just before and at the study completion. Plasma coenzyme Q(10) concentrations were determined initially and at each study visit. Parents reported adverse events and study drug evaluations using standardized forms. Most of the 16 children who completed this study tolerated high-dose coenzyme Q(10) well. Uncooperative behavior resulted in premature withdrawal of two participants, and may have been treatment-related. Pre- and posttreatment laboratory test changes were considered to be clinically nonsignificant. Study results indicate that high-dose coenzyme Q(10) (10 mg/kg/day) is well-absorbed and well-tolerated by most children with Down syndrome, and appears to provide plasma concentrations which are comparable to previous adult studies administering much higher coenzyme Q(10) dosages.

Functional magnetic resonance imaging of cognitive processing in young adults with Down syndrome.

The authors used functional magnetic resonance imaging (fMRI) to investigate neural activation during a semantic-classification/object-recognition task in 13 persons with Down syndrome and 12 typically developing control participants (age range  =  12-26 years). A comparison between groups suggested atypical patterns of brain activation for the individuals with Down syndrome. Correlation analyses between an index of visual spatial ability and brain activation depicted a positive relationship between (a) this index and brain activation in regions of the occipital and parietal lobes for the typically developing individuals and (b) the middle and dorsal frontal gyri in the individuals with Down syndrome. These findings supported the authors' hypothesis that persons with Down syndrome demonstrate atypical neural activation compared with typically developing individuals matched for chronological age.

Blood expression profiles for tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome.

Blood gene expression profiling has been applied to a variety of hematological malignancies, autoimmune disorders, and infectious diseases. This study applies this approach to genetic diseases without obvious blood phenotypes. Three genetic diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and Down's syndrome were compared with a group of healthy controls. RNA from whole blood was surveyed using Affymetrix U133A arrays. Each disease was associated with a unique gene expression pattern in blood that can be accurately distinguished by a classifier. Genes on chromosome 21 were overexpressed in Down's syndrome, and genes controlling cell cycle and proliferation were associated with tuberous sclerosis complex type 2 or neurofibromatosis type 1. A subset of genes involved in cardiac development or remodeling were overexpressed in patients with Down's syndrome and congenital heart defects. These findings suggest that blood gene expression profiling on a broader basis might be useful for genetic disease screening/diagnosis and might help elucidate mechanisms and pathways that lead to genotype-phenotype differences.