Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways.

Autism spectrum disorder (ASD) is a group of complex, neurological disorders that affect early cognitive, social, and verbal development. Our understanding of ASD has vastly improved with advances in genomic sequencing technology and genetic models that have identified >800 loci with variants that increase susceptibility to ASD. Although these findings have confirmed its high heritability, the underlying mechanisms by which these genes produce the ASD phenotypes have not been defined.

Mitochondrial and ion channel gene alterations in autism.

To evaluate the potential importance in autistic subjects of copy number variants (CNVs) that alter genes of relevance to bioenergetics, ionic metabolism, and synaptic function, we conducted a detailed microarray analysis of 69 autism probands and 35 parents, compared to 89 CEU HapMap controls. This revealed that the frequency CNVs of≥100kb and CNVs of≥10 Kb were markedly increased in probands over parents and in probands and parents over controls. Evaluation of CNVs≥1Mb by chromosomal FISH confirmed the molecular identity of a subset of the CNVs, some of which were associated with chromosomal rearrangements.

Acute hemodialysis for hyperammonemia in small neonates.

Neonatal metabolic emergencies require a multidisciplinary team approach for supportive management that has increasingly come to feature renal replacement therapies in addition to nutritional support, the use of pharmaceutical agents, and testing to guide management and provide a definitive diagnosis. An increased appreciation for the mechanisms involved in ammonia neurotoxicity has placed greater emphasis on the need for its rapid yet safe resolution to optimize long-term prognosis. We examined our experience of intermittent hemodialysis (HD) and considered (1) the feasibility of HD in low-weight neonates, (2) the rate of decrease in ammonia, (3) complications during HD in small neonates weighing <4 kg presenting at University Children's Hospital between 1999 and 2002.