Background: X-linked adrenoleukodystophy (X-ALD)(MIM 300100) results in inflammatory demyelination of the brain and spinal cord. The severity of MRI abnormality assessed with Loes score has a high predictive value. Objective: In X-ALD localization of the initial cerebral lesion can be more predictive about the severity of neuropsychologic impairment when similar MRI scores are encountered. Material/Methods: 28 patients with childhood cerebral X-ALD followed between 1991-2010 were studied. MR images, Loes scores; neurologic examination, X-ALD neurologic severity scale; Denver II test from 0-6 years, Wechsler Intelligence Scale for Children-Revised (WISC-R) from 6-16 years were evaluated. Results: 28 patients were grouped according to the pattern of cerebral involvement. Groups with parietooccipital (15), frontal (4), diffuse (2), cerebellar (1), corpus callosum (3) and no involvement (3) Objective: To evaluate the tolerability and effectiveness of treatment of pre-symptomatic X-ALD with lovastatin/coenzyme Q10 for the prevention of acute cerebral disease. Methods: Open-label, treatment of pre-symptomatic XL-ALD males <18 yrs old, with lovastatin, 1 mg/kg (max 40 mg) and coenzyme Q10 50-60 mg per day. Results: Seven pre-symptomatic boys currently aged 20.3±4.0 yrs were treated with 10-40 mg lovastatin and 50-60 mg coenzyme Q10 daily from age 8.5±3.5 yrs (3.3-12.6). One developed early MRI evidence of progression at age 5 yrs and underwent hematopoietic stem cell transplantation (HSCT). A second boy developed early signs of adrenomyeloneuropathy (AMN) at age 20 yrs. Of 16 boys who were never treated with lovastatin/coenzyme Q10, 3 are deceased (mean age 9.7±1.4 yrs), 3 are asymptomatic (mean age 12 yrs), 1 has adrenal insufficiency, and 9 have severe neurological impairment (mean age 14±6.3 yrs). No effect was demonstrated on plasma very long-chain fatty acids. Conclusion: Pre-symptomatic treatment of XL-ALD may prevent the development of acute cerebral degeneration; however, it does not appear to prevent the development of AMN. Further clinical trials are indicated. Structural variations of human genome emerge as novel major contributors to genetic diversity and disease susceptibility. Copy number variations, CNVs, are known to be involved in Mendelian disorders. Adrenoleukodystrophy X linked (XALD) is a rare disorder with two main phenotypes, a childhood form with cerebral involvement (CCALD) and a mild, adrenomieloneuropathy (AMN),adult chronic, that affects axonal tracts of the spinal cord. Both forms can be triggered by the same genetic mutation, indicating a participation of a modifier gene and or environmental factors. Therefore, to gain insight into what might be the potential source contributing to the differential phenotypes evolution we studied the CNV of genes involved in fatty acid metabolism, the inflammatory response and cell reparation. By using Illumina SNP data, Sentrix HumanHap 1 M-SNPs, we analyzed 8 XALD patients either with CCALD and AMN pure phenotypes. For gene candidate study (34) we used the semi-quantitative screening multiplex ligament-dependent probe amplification (MLPA) applied to 41 AMN, 46 CCALD and 26 Controls from Spain and Brazil. We found variable levels of AGPTA2, ABCA2, SLC27A2, SLC25A22, PCDH17, PCDH20, PNPLA2 . The data obtained may contribute to elucidation of clinical heterogeneity in XALD patients and to design specific therapeutic approaches. Mutations in PEX19 cause peroxisomal biogenesis disorders. PEX19 encodes a cytosolic protein that interacts with peroxisomal membrane proteins (PMPs) and functions as a cycling PMP-receptor protein. Besides full-length PEX19, the splice variant PEX19DeltaE2 accounts for a significant level of total PEX19 mRNA. Even though production of a protein was suggested by in vitro translation, PEX19DeltaE2 was shown not to complement PEX19 deficient cells. In the present work, we quantified PEX19DeltaE2 by real-time PCR showing significant variations among tissues. Furthermore, we found an increase in PEX19DeltaE2 mRNA upon inhibition of translation suggesting a sensitization to NMD without complete degradation. Using BRET, we showed that PEX19DeltaE2 has the capacity to bind PMPs. Nevertheless, PEX19DeltaE2 shows a distinct interaction pattern to the full-length protein lacking the interaction with PEX14, PEX13, and PEX10. This finding may explain that PEX19DeltaE2 is not able to restore the import of peroxisomal matrix proteins in PEX19 deficient cells.