Urinary polycyclic aromatic hydrocarbon metabolites and attention/deficit hyperactivity disorder, learning disability, and special education in U.S. children aged 6 to 15.

Exposure to polycyclic aromatic hydrocarbons (PAHs) adversely affects child neurodevelopment, but little is known about the relationship between PAHs and clinically significant developmental disorders. We examined the relationship between childhood measures of PAH exposure and prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), and special education (SE) in a nationally representative sample of 1,257 U.S. children 6-15 years of age. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. PAH exposure was measured by urinary metabolite concentrations. Outcomes were defined by parental report of (1) ever doctor-diagnosed ADHD, (2) ever doctor- or school representative-identified LD, and (3) receipt of SE or early intervention services. Multivariate logistic regression accounting for survey sampling was used to determine the associations between PAH metabolites and ADHD, LD, and SE. Children exposed to higher levels of fluorine metabolites had a 2-fold increased odds (95% C.I. 1.1, 3.8) of SE, and this association was more apparent in males (OR 2.3; 95% C.I. 1.2, 4.1) than in females (OR 1.8; 95% C.I. 0.6, 5.4). No other consistent pattern of developmental disorders was associated with urinary PAH metabolites. However, concurrent exposure to PAH fluorine metabolites may increase use of special education services among U.S. children.

Association between phthalates and attention deficit disorder and learning disability in U.S. children, 6-15 years.

OBJECTIVE: This study investigates the association between urinary phthalate metabolite levels and attention deficit disorder (ADD), learning disability (LD), and co-occurrence of ADD and LD in 6-15-year-old children. METHODS: We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, 2001-2004). Phthalate metabolites with ≥75% detection in urine samples were examined. The study population comprised 1493 children with parent-reported information on ADD or LD diagnosis and phthalate concentrations in urine. Phthalate concentrations were creatinine-adjusted and log10-transformed for analysis. All models controlled for child sex, age, race, household income, blood lead, and maternal smoking during pregnancy. RESULTS: There were 112 ADD cases, 173 LD cases, and 56 ADD and LD cases in the sample. After adjusting for potential confounders, we found increased odds of ADD with increasing urinary concentration of di-2-ethylhexyl phthalates (OR: 2.1; 95% CI: 1.1, 3.9) and high molecular weight phthalates (OR: 2.7; 95% CI: 1.2, 6.1). In addition, dibutyl phthalates (OR: 3.3; 95% CI: 0.9, 12.7) and high molecular weight phthalates (OR: 3.7; 95% CI: 0.9, 14.8) were marginally associated with increased odds of co-occurring ADD and LD. We did not find associations for any phthalate and LD alone. We observed stronger associations between phthalates and ADD and both ADD and LD in girls than boys in some models. CONCLUSIONS: We found cross-sectional evidence that certain phthalates are associated with increased odds of ADD and both ADD and LD. Further investigations with longitudinal data are needed to confirm these results.

Bisphenol A in relation to behavior and learning of school-age children.

BACKGROUND: Bisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. METHODS: Urinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8-11 years. The main outcome measures were the Child Behavior Checklist (CBCL) and the Learning Disability Evaluation Scale (LDES). RESULTS: Urinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons. CONCLUSIONS: Environmental exposure to BPA might be associated with childhood behavioral and learning development. The results suggest possible nonmonotonic relationships.

Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability.

Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this gene result in HSD10 deficiency, whereas a silent mutation results in mental retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense mutation found in the HSD17B10 gene, namely c.194T>C transition (rs104886492), brought about by the loss of two forked methyl groups of valine 65 in the HSD10 active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a neurological syndrome with metabolic derangements, choreoathetosis, refractory epilepsy and learning disability. He has no history of acute decompensation or metabolic acidosis whereas his urine organic acid profile, showing elevated levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of HSD10 deficiency. His HSD10 activity was much lower than the normal control level, with normal ß-ketothiolase activity. The c.194T>C mutation in HSD17B10 can be identified by the restriction fragment polymorphism analysis, thereby facilitating the screening of this novel mutation in individuals with intellectual disability of unknown etiology and their family members much easier. The patient's mother is an asymptomatic carrier, and has a mixed ancestry (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency patients are not confined to a particular ethnicity although previously reported cases were either Spanish or German descendants.

Urine screening for clients with learning disabilities.

This article describes a study carried out to explore how common urinary tract infections are among adults with learning disabilities who use continence products. The study also evaluated the use of a product to assist urine sample collection with this client group.

[Neuroradiologic findings of glutaric aciduria type I]. / Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I.

Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging findings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissures.

Mild learning difficulties and offending behaviour--is there a link with monoamine oxidase A deficiency?

We have attempted to replicate the findings of Brunner et al., who described a large Dutch kindred where several males were of borderline intelligence and showed characteristically aggressive and sometimes dangerous or extremely antisocial behaviour. The genetic defect for this syndrome was assigned to the p11-p21 region of the X chromosome following linkage analysis in a single kindred. Subsequent sequencing of a candidate gene, monoamine oxidase A (MAO-A), at the position of maximum linkage revealed a causative mutation in the coding region of the MAO-A gene in position 936. In addition to identifying both the phenotype and the associated mutation found by Brunner et al., we also wished to test the hypothesis that mutations elsewhere in the MAO-A gene could cause the low intelligence quotient/personality disorder phenotype associated with low urinary catecholamine degradation products. Fifty-four male subjects similar in clinical characteristics to the affected males in the Dutch kindred were identified within secure mental health facilities in England and Wales. All were assessed using the antisocial personality disorder section of the SCID-II interview instrument, and information about their offending behaviour and family history was obtained from the medical notes. A blood and early-morning urine sample was obtained from each patient. Analysis of urinary excretion patterns of biogenic amines and their metabolites, represented as ratios of normetanefrine to vanillylmandelic acid, revealed two possible cases of MAO-A deficiency, which were found to be negative after resampling.

[Neurochemical and neurotransmitter studies in patients with learning disabilities].

To clarify the pathophysiology of learning disability (LD), we measured the urinary levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), and phenylethylamine (PEA) in urine samples collected in a 24 hour period. Findings were compared with those obtained in age-matched controls and diseased controls including patients with attention deficit-hyperactivity disorder (ADHD), infantile autism, and mental retardation. The mean urinary level of MHPG in LD (n = 6) were not significantly different from those in ADHD (n = 16), mental retardation (n = 4), infantile autism (n = 5), and the controls (n = 6), while the mean urinary levels of PEA were significantly lower in LD (n = 6, 91 +/- 17.3 micrograms/mg) and in ADHD (n = 5, 65 +/- 53.6 micrograms/mg) as compared to age-matched controls (n = 3, 340 +/- 264.5 micrograms/mg) ANOVA, (p < 0.05). PEA is considered to play an important role for the pathogenesis of LD and ADHD.

Norepinephrine and dopamine metabolites and educational variables in boys with attention deficit disorder and hyperactivity.

The present study evaluated the biochemical measures of urinary homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in relation to functioning on selected psychoeducational tests in a group of boys with attention deficit disorder and hyperactivity. The Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT), and the Peabody Picture Vocabulary Test were administered to 28 hyperactive and 23 control subjects. The findings suggest subtle differences in psychoeducational test performance in relation to specific levels of homovanillic acid and MHPG.

Lead and hyperactivity revisited. An investigation of nondisadvantaged children.

The purposes of this study were to examine whether hyperactive children had elevated lead levels, to assess whether lead levels were associated with poor psychometric performance in hyperactive children, and to replicate previous reports of hyperactive children with perinatal insult having lower lead levels than those with normal perinatal history. Hyperactive, learning-disabled children and normal siblings were studied. The hyperactive children had higher chelated urine lead levels than their own siblings. Other contrasts were not significant. Cognitive performances and lead levels were weakly associated in the hyperactive sample. Contrary to previous reports, lead levels and perinatal complications were not negatively correlated. These results support the notion that lead levels are weakly associated with hyperactive disorders.