Novel PEX3 Gene Mutations Resulting in a Moderate Zellweger Spectrum Disorder.

BACKGROUND: Peroxisome biogenesis disorders (PBDs) may have a variable clinical expression, ranging from severe, lethal to mild phenotypes with progressive evolution. PBDs are autosomal recessive disorders caused by mutations in PEX genes, which encode proteins called peroxins, involved in the assembly of the peroxisome. Patient Description: We herein report a patient who is currently 9 years old and who is compound heterozygous for two novel mutations in the PEX3 gene. RESULTS: Mild biochemical abnormalities of the peroxisomal parameters suggested a Zellweger spectrum defect in the patient. Sequence analysis of the PEX3 gene identified two novel heterozygous, pathogenic mutations. CONCLUSION: Mutations in PEX3 usually result in a severe, early lethal phenotype. We report a patient compound heterozygous for two novel mutations in the PEX3 gene, who is less affected than previously reported patients with a defect in the PEX3 gene. Our findings indicate that PEX3 defects may cause a disease spectrum similar as previously observed for other PEX gene defects.

Degradation of 2,4-dichlorophenoxyacetic acid (2,4-d) by a hypersaline microbial mat and related functional changes in the mat community.

Microbial mats possibly possess degradation capacities for haloorganic pollutants because of their wide range of different functional groups of microorganisms combined with extreme diurnal changes in pH, oxygen, and sulfide gradients. In this study, 20 mg/l of the chlorinated herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was applied to a pristine hypersaline cyanobacterial mat from Guerrero Negro, Mexico, under a light regime of 12 h dark/12 h light (600 mumol photons/m(2)s). The loss of 2,4-D was followed by chemical GC analysis; functional changes within the mat were determined with microelectrodes for oxygen, photosynthesis, pH, and sulfide. The depletion of 2,4-D due to photooxidation or sorption processes was checked in control experiments. Within 13 days, the light/dark incubated mats degraded 97% of the herbicide, while in permanent darkness only 35% were degraded. Adsorption of 2,4-D to the mat material, agar, or glass walls was negligible (4.6%), whereas 21% of the herbicide was degraded photochemically. The 2,4-D removal rate in the light/dark incubations was comparable to values reported for soils. The phototrophic community of the mat was permanently inhibited by the 2,4-D addition by 17% on average. The sulfate reduction in the entire mat and the respiration in the photic zone were inhibited more strongly but returned to original levels. Since at the end of the experiment the photosynthetic and respiratory activity of the mats were almost as high as in the beginning and 2,4-D almost completely disappeared, we conclude that the examined mats represent a robust and effective system for the degradation of the herbicide where probably the aerobic heterotrophic population is a major player in the degradation process.

Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis.

To test the efficacy of a combined alpha- and beta-receptor agonist in acute bronchiolitis, we compared inhaled racemic epinephrine with salbutamol in a double-blind, crossover, randomized protocol. Twenty-four infants, 4.6 +/- 0.5 (mean +/- SEM) months of age, with their first episode of bronchiolitis were tested. After sedation with chloral hydrate, a clinical score and pulmonary mechanics measurements using simultaneous signals of airflow volume and transpulmonary pressure were recorded. After baseline measurements, infants received either nebulized salbutamol, 0.03 ml/kg, or racemic epinephrine, 0.1 ml/kg. Thirty minutes later, there was a significant decrease in clinical score after treatment with racemic epinephrine compared with the baseline score (p < 0.001); this difference was not present after salbutamol inhalation (p = 0.42). Only 13 patients had a decrease in clinical score after salbutamol therapy, in comparison with 20 infants treated with racemic epinephrine (p < 0.01). Both drug decreased respiratory rate, but the decrease was greater after the use of racemic epinephrine (p < 0.001). There was a significant decrease in inspiratory, expiratory, and total pulmonary resistance after treatment with racemic epinephrine compared with baseline values (p < 0.01) but no significant change after salbutamol inhalation. There was no significant correlation between the clinical score and pulmonary mechanics either at baseline or after drug treatment. We conclude that racemic epinephrine is superior to salbutamol in the treatment of infants with their first episode of acute bronchiolitis.