Exercise Tolerance Testing in a Prospective Cohort of Adolescents with Chronic Fatigue Syndrome and Recovered Controls following Infectious Mononucleosis

OBJECTIVE: Six months following acute infectious mononucleosis (IM), 13%, of adolescents meet criteria for chronic fatigue syndrome (CFS). We measured exercise tolerance in adolescents with CFS and controls 6 months following IM. STUDY DESIGN: 21 adolescents with CFS 6 months following IM and 21 recovered controls performed a maximal incremental exercise tolerance test with breath-by-breath gas analysis. Values expressed are mean ± standard deviation. RESULTS: The adolescents diagnosed with CFS and controls did not differ in age, weight, body-mass index or peak work capacity. Lower VO(2) (oxygen consumption) peak percent of predicted was seen in adolescents with CFS compared with controls (CFS 99.3 ± 16.6 vs control 110.7 ± 19.9, p = 0.05). Peak oxygen pulse also was lower in adolescents with CFS compared with recovered controls (CFS 12.4 ± 2.9 vs controls 14.9 ± 4.3, p = 0.03). CONCLUSIONS: Adolescents with CFS 6 months following IM have a lower degree of fitness and efficiency of exercise than recovered adolescents. Whether these abnormal exercise findings are a cause or effect of CFS is unknown. IM can lead to both fatigue and measurable changes in exercise testing in a subset of adolescents

ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies

ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. In this report, we present a cohort of 11 affected individuals from six unrelated families with a complicated form of hereditary spastic paraplegia (HSP) who carry bi-allelic deleterious variants in ABHD16A. Affected individuals present with a similar phenotype consisting of global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies. Immunoblot analysis on extracts from fibroblasts from four affected individuals demonstrated little to no ABHD16A protein levels compared to controls. Our findings add ABHD16A to the growing list of lipid genes in which dysregulation can cause complicated forms of HSP and begin to describe the molecular etiology of this condition

Genome-Wide Association Study of Multiplex Schizophrenia Pedigrees

Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and UK (N = 5433). Samples from Australia were collected in two studies, in 1993-1996 and 2002-2005 and from UK in 1991-1992. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant single nucleotide polymorphism (SNP), rs1805313 (P = 3.91 × 10(-14) for lead concentration in a meta-analysis of all data), is known to have effects on ALAD expression in blood cells but other SNPs affecting ALAD expression did not affect blood lead. Variants at 12 other loci, including ABO, showed suggestive associations (5 × 10(-6) > P > 5 × 10(-8)). Identification of genetic polymorphisms affecting blood lead reinforces the view that genetic factors, as well as environmental ones, are important in determining blood lead levels. The ways in which ALAD variation affects lead uptake or distribution are still to be determined