Evaluation of two year treatment outcome and limited impact of arginine restriction in a patient with GAMT deficiency.

A 4-year-old female with history of developmental regression and autistic features was diagnosed with guanidinoacetate methyltransferase deficiency at age 21 months. Upon treatment, she showed improvements in her developmental milestones, sensorial-neural hearing loss and brain atrophy on cranial-MRI. The creatine/choline ratio increased 82% in basal ganglia and 88% in white matter on cranial MR-spectroscopy. The CSF guanidinoacetate decreased 80% after six months of ornithine and creatine supplementation and an additional 8% after 18 months of additional arginine restricted diet. We report the most favorable clinical and biochemical outcome on treatment in our patient.

An item response theory analysis of the Parenting Stress Index-Short Form with parents of children with autism spectrum disorders.

BACKGROUND: The Parenting Stress Index-Short Form (PSI-SF) is one of the most widely used instruments for measuring parenting stress in families of children with autism spectrum disorders (ASD). However, no research to date has examined the psychometric properties of the PSI-SF in a sample of parents of young children with ASD. In this regard, item response theory (IRT) can be used to estimate how much information or discrimination each item of a scale offers across the entire range of the latent variable being measured, by creating individual item information curves or profiles. The purpose of this study was to use IRT to examine the discriminability of PSI-SF items in a sample of parents of young children with ASD who experience varying levels of parental stress. METHODS: The study involved the parents of 141 children with autism spectrum disorders (91.4% mothers; mean age 36.2 years) who completed the PSI-SF following diagnosis. Item characteristic curves were constructed for each of the PSI-SF items and examined with regard to item functioning. RESULTS: Results indicated that, for the most part, changes in parental distress severity were reflected in changes on item scores. However, several items on the subscales measuring parent-child dysfunctional interactions and child behavior difficulty functioned poorly to discriminate parents across a range of total stress severity. CONCLUSIONS: The parent-child dysfunctional interaction and difficult child subscales of the PSI-SF scale should be used with caution with parents of young children with ASD. More research is required to examine PSI-SF content validity, at least among parents of children with ASD and perhaps parents of children with other disabilities as well.

Mechanism of repression by Bacillus subtilis CcpC, a LysR family regulator.

Bacillus subtilis CcpC is a LysR family transcriptional regulatory protein that negatively regulates genes encoding enzymes of the tricarboxylic acid branch of the Krebs cycle. In the present work, the promoter region of the aconitase (citB) gene was used to investigate the mechanism of repression by CcpC. The binding of CcpC to the citB promoter region was shown to depend on DNA elements located near positions -66 and -27. Binding to these elements induced a bend in the DNA at position -41. Introduction of mutations in the -27 region and the presence of citrate, the inducer, had similar effects. In either case, citB expression was derepressed in vivo, the affinity of CcpC binding was reduced in vitro, the angle of the bend was relaxed, and RNA polymerase gained greater access to the -35 region of the promoter.