Arteria subclavia derecha aberrante aislada. Reporte de un caso / Isolated aberrant right subclavian artery. A case report

Resumen La arteria subclavia derecha aberrante (ARSA) es la anomalía del arco aórtico más común. La probabilidad de hallar un ARSA durante un estudio ecográfico es de alrededor de 1%. En aquellos fetos con ARSA, la probabilidad de tener otros hallazgos cardiacos y/o extracardiacos o una anomalía cromosómica es elevada. La prevalencia de la relación del ARSA con el síndrome de Down es de aproximadamente 20%, por lo que este marcador puede contribuir al asesoramiento del síndrome de Down en el segundo trimestre y probablemente en el primer trimestre. La recomendación ante el hallazgo de ARSA es realizar un estudio detallado de la anatomía fetal en busca de otros marcadores de aneuploidías y realizar ecocardiografía fetal. La realización de estudios invasivos quedará limitado a aquellas situaciones en donde además del ARSA se encuentren otros marcadores u otras condiciones que aumenten el riesgo de síndrome de Down. Sin embargo, ante el hallazgo de ARSA aislado, el incremento en el riesgo es igual a cero, pudiendo considerarse una variante de la normalidad.

Abstract An aberrant right subclavian artery (ARSA) is the most common branch abnormality of the aortic arch. It can be identified by ultrasound scan in 1% of cases. The probability of association with cardiac and/or extracardiac anomalies, as well as chromosomal abnormality, is high. Prevalence of ARSA with Down syndrome is approximately 20%, and this marker may contribute to counseling on Down syndrome during the second trimester and maybe in the first trimester. When ARSA is found, recommendations include a detailed study of the fetal anatomy for other markers of aneuploidy and to obtain a fetal echocardiogram. Invasive studies will be limited to those situations where, in addition to ARSA, other markers or other conditions that increase the risk of Down syndrome are found. However, the finding of an isolated ARSA increases the risk to zero and is considered a normal variant.

Gene therapy for neurodegenerative disorders: advances, insights and prospects

Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders, highlighting promising technologies, targets, and future prospects.

Analysis of ARSA gene variant in an infant with late infantile metachromatic leukodystrophy / 中华医学遗传学杂志

Objective@#To detect pathogenic variant of ARSA gene in an infant with late infantile metachromatic leukodystrophy (MLD).@*Methods@#The male proband had an onset of walking dysfunction and seizure at 28 months. Arylsulfatase A activity of his peripheral blood leucocytes was 26.9 nmol/mg.17h, and cranial MRI showed wild symmetrical demyelination. With genomic DNA extracted from his peripheral blood sample, all coding exons and splicing sites of the ARSA gene were subjected to Sanger sequencing. PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. Ucsf chimera software was used to analyze the impact of candidate variants on the secondary structure of the protein product. Impact of potential variants was also analyzed with software including PolyPhen-2, Mutation Taster, SIFT and PROVEAN. Whole-exome sequencing was carried out to identify additional variants which may explain the patient’s condition.@*Results@#The proband was found to harbor compound heterozygous variants of the ARSA gene [c.467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*)], neither of which was reported previously. As predicted by Ucsf chimera software, the c. 960G>A (p.Trp320*) variant may demolish important secondary structures including α-helix, β-strand and coil of the ARSA protein, causing serious damage to its structure and loss of function. The c. 467G>A (p.Gly156Asp) variant was predicted to be "probably damaging" by PolyPhen-2, Mutation Taster and SIFT software.@*Conclusion@#The patient’s condition may be attributed to the compound heterozygous c. 467G>A (p.Gly156Asp) and c. 960G>A (p.Trp320*) variants of the ARSA gene. Above results have facilitated genetic counseling and prenatal diagnosis for this family.

Management Of Genital Warts Through Ayurveda-a Case Report

External genital warts or Condyloma Acuminata is caused by the Human Papilloma Virus subtypes 6 and 11. According to Ayurveda it can be diagnosed as Yoni Arsa. This case report presents a 51 yr old female with the complaints of per vaginal discharge, itching and appearance of progressively increasing number of lesions in the vulva for 6 months. The pathological diagnosis of the vulvar lesion specimen was Condyloma Acuminata. Patient was treated with internal administration and external application of Ayurvedic medicines. Considerable relief for the condition was noted and the follow up visits confirmed the non recurrence of the disease. Ayurvedic interventions can be considered as minimal invasive and cost effective in the management of genital warts.

Metachromatic leukodystrophy / 国际儿科学杂志

Metachromatic leukodystrophy is an inherited lysosomal disorder caused by autosomal reces-sive mutations of ARSA gene or PASP gene,which result in the accumulation of sulfatides in the central and pe-ripheral nervous system leading to demyelination. The disease is classified into a late-infantile,juvenile and adult onset type based on the age of onset,all characterized by a variety of neurological symptoms,which eventually lead to death if untreated. There is no curative treatment for all types and stages. This review discusses pathogen-esis,clinical manifestations,diagnostic process and efficacy of current and possible future therapies such as en-zyme replacement therapy,hematopoietic stem cell transplantation and gene therapy. A longer follow up period for the above therapies are needed to come to a general conclusion and improve treatment options for metachro-matic leukodystrophy.

Identification of a novel mutation in ARSA gene in three patients of an Iranian family with metachromatic leukodystrophy disorder

Abstract Metachromatic leukodystrophy disorder (MLD) is an autosomal recessive and lysosomal storage disease. The disease is caused by the deficiency of the enzyme arylsulfatase A (ARSA) which is encoded by the ARSA gene. Different mutations have been reported in different populations. The present study was aimed to detect the mutation type of the ARSA gene in three relative Iranian patients. We found a novel homozygous missense mutation c.1070 G > T (p.Gly357Val) in exon 6 of these patients. The mutation was found to be reported for the first time in MLD patients. The data can update the mutation profile and contribute toward improved clinical management and counseling of MLD patients.

A Korean Patient with Early Juvenile Form of Metachromatic Leukodystrophy: Biochemical and Molecular Genetic Investigation

Metachromatic leukodystrophy is an inherited lysosomal storage disorder caused by the deficiency of arylsulfatase A activity. The patient in this study, a 5-yr-old girl, presented with progressive psychomotor regression. An MRI image of her brain showed bilateral symmetrical demyelination. The arylsulfatase A activity in her leukocytes was decreased to 8.0 nmol/hr/mg protein (reference range, 25-80 nmol/hr/mg protein). Mutation analysis of ARSA, using PCR and direct sequencing, showed two heterozygote pathogenic variations of c.449C>T (p.Pro150Leu) and c.640G>A (p.Ala214Thr). In summary, we report a Korean patient with an early juvenile form of metachromatic leukodystrophy, who was diagnosed based on her clinical symptoms as well as by using biochemical, radiological, and molecular genetic investigations.

A Case of Metachromatic Leukodystrophy Confirmed by Molecular Genetic Analysis / 대한소아신경학회지

Metachromatic leukodystrophy (MLD) is the rare neurometabolic disease caused by the deficiency of the enzyme arylsulfatase A resulting in a deficiency of sulfatide degradation and the target gene is ARSA gene. We report a case of the late infantile form of MLD that was confirmed by means of enzyme assay and gene analysis with typical brain MRI and MR spectroscopy finding.

Identification of a Novel Splicing Mutation in the ARSA Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy / 대한진단검사의학회지

Metachromatic leukodystrophy (MLD; MIM 250100), a severe neurodegenerative disorder inherited as an autosomal recessive trait, is caused by mutations in the arylsulfatase A (ARSA) gene. Although several germ line ARSA mutations have been identified in patients with MLD of various ethnic backgrounds elsewhere in the world, no genetically confirmed cases of MLD have been reported in Korea. Recently, we identified a mutation in the ARSA gene of a Korean male with MLD. A male infant with late-infantile form of MLD had been admitted to our hospital for further examination. His neuromuscular symptoms, which included inability to walk at the age of 12 months, gradually worsened, even after allograft bone marrow transplantation; he died at the age of 9 yr. His elder brother had also been diagnosed with MLD. To confirm the presence of a genetic abnormality, all the coding exons of the ARSA gene and the flanking introns were amplified by PCR. A molecular analysis of the ARSA gene revealed both a novel heterozygous splicing mutation (c.1101+1G>T) in intron 6 and a heterozygous missense mutation in exon 2 (c.296G>A; Gly99Asp). The patient's elder brother who had MLD is believed to have had the same mutation, which may be correlated with a rapidly deteriorating clinical course. This study identified a novel mutation in the ARSA gene, related to a late-infantile form of MLD with a lethal clinical course and suggested that molecular diagnosis of patients may be useful in early diagnosis and for deciding intervention measures for their family members.