Evidence of oxidative stress in peroxisomal disorders

<p><b>INTRODUCTION</b>Peroxisomal disorders are subdivided into peroxisome biogenesis disorders (PBDs) and single peroxisomal enzyme deficiency. Many peroxisomal diseases exhibit excessive oxidative stress, leading to neurological alterations and dysfunction. Peroxisomes use oxygen in oxidative reactions that generate hydrogen peroxide. This study aimed to investigate various oxidative stress parameters in patients suffering from peroxisomal disorders.</p><p><b>METHODS</b>A total of 20 patients with peroxisomal disorders, aged six months to 13 years (mean age 5.9 ± 3.2 years), were compared to 14 healthy controls. All individuals were subjected to full history-taking, including a three-generation pedigree analysis concerning parental consanguinity and similarly affected members in the family, with meticulous clinical examination to detect any malformation or anomaly. Estimation of very-long-chain fatty acids and phytanic acid was done to verify the diagnosis. Brain magnetic resonance imaging, electroencephalogram, visual evoked potential, auditory potential and plain radiography were conducted to assess the pathological condition of the patients. Oxidative stress parameters, including nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD), were estimated in both the patients and controls.</p><p><b>RESULTS</b>Significant increases in both MDA and NO were found in patients with PBDs. It was also demonstrated that SOD was significantly lower in patients with PDB than the controls.</p><p><b>CONCLUSION</b>This study sheds more light on the link between oxidative stress and peroxisomal disorders, as oxidative stress may be a hallmark of peroxisomal disorders. Consequently, one of the useful neuronal rescue strategies could be treatment with antioxidant agents in addition to other lines of treatments.</p>

Genetic studies of limb reduction defects

Limb reduction defects are an important group of congenital limb malformations that requires thorough assessment. They can be isolated or associated with other malformations as a part of syndrome. Causes of limb deficiencies include single gene disorders, chromosomal abnormalities or teratogens. However, the etiology remains unknown in many cases. The present study aimed at the proper diagnosis and classification of cases with limb defects referred to the Limb Malformations Clinic, NRC in order to provide accurate and efficient genetic counseling. The study included 22 cases [14 males, 8 females] with limb reduction defects, their ages at presentation ranged between 20 days and 16 years. Detailed history including teratogen exposure and affected family members, three generation pedigree analysis, complete examination of different body systems with specific studies of different parts of the limbs documented by radiological examination, photography and basic anthropometric measurements were conducted for all cases. Dermatoglyphic analysis, cytogenetic studies and other investigations were done whenever indicated. Cases were classified according to Temtamy and McKusick [1] based on both anatomical and genetic considerations into 8 groups; isolated terminal transverse defects [n=5, cases 1-5= 22.7%], terminal transverse defect as a part of syndrome [n=1, case 6= 4.54%], isolated radial defect [n=1, case 7= 4.54%], radial defect as a part of syndrome [n= 7, cases 8-14= 31.8%], isolated ulnar defect [n= 2, cases 15, 16= 9.09%], ulnar defect as a part of syndrome [n= 3, cases .17-19= 13.6%], pre and postaxial defect [n= 1, case 20= 4.54%] and axial defect as a part of syndrome [n=2, cases 21, 22= 9.09%]. The results of this study have shown that limb absence or reduction defects are not an uncommon malformation among Egyptian children. Delineation of the exact cause, correct classification and proper diagnosis are needed to face this disabling chronic problem. Molecular studies are recommended for proper diagnosis, genetic counseling and understanding of the pathogenesis