Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

Energy expenditure in children with Down syndrome: correcting metabolic rate for movement.

Children with Down syndrome (DS) have a high prevalence of obesity. To investigate the relation between energy expenditure and obesity, we measured body composition, resting metabolic rate (RMR), and total energy expenditure in 13 prepubescent children with DS and in 10 control subjects matched for age, weight, and percentage of fat, using indirect calorimetry and the doubly labeled water method. Measurement of RMR was complicated by excessive movement by both the DS and control subjects. We therefore developed a method of subtracting the energy expended in movement and calculated the corrected RMR. The corrected RMR was significantly lower in those with DS than in control subjects when expressed as a percentage of the basal metabolic rate, predicted by the World Health Organization: 79.5% +/- 10.4% and 96.8% +/- 7.8%, respectively (p < 0.001). No significant differences were detected in total daily energy expenditure or non-RMR expenditure between the subject groups. In the DS group, 60% of the variability in fat mass could be accounted for by non-RMR expenditure expressed per kilogram of body weight (p < 0.02). No relation was detected between fat mass and non-RMR expenditure in control subjects, nor were any measures of energy expenditure predictive of changes in fatness among the subjects with DS during a 1-year follow-up. The results of this study indicate that prepubescent children with DS have decreased RMR compared with control children.

Hearing loss in children with Down syndrome.

Conventional behavioral testing of hearing shows that children with Down syndrome have a high prevalence of hearing deficits. However, most young (< 3.5 years of age) children with Down syndrome are unable to cooperate in this type of testing. We evaluated auditory brain-stem responses of 47 unselected patients 2 months to 3 1/2 years of age. Thirty-four percent had normal hearing, 28% had unilateral loss, and 38% had bilateral loss. Type of loss was conductive in 19 ears, mixed in 14, and sensorineural in 16. Degree of loss was mild in 33 ears, moderate in 13, and severe to profound in 3. Language quotients and degree of hearing loss were compared and an association was not found. Because of the high prevalence of hearing loss in children with Down syndrome, we recommend evaluation of auditory brain-stem responses in the first 6 months of life.