Errores innatos del metabolismo. avances en el diagnostico y terapeutica / Inborn errors of metabolism. Advances in diagnosis and therapeutic

Resumen Las novedades en el campo de los errores innatos del metabolismo (EIM) son espectaculares. Se han descrito nuevos EIM, se conoce mejor sus bases fisiopatológicas y las implicaciones para el organismo. Con la llegada de las nuevas técnicas de metabolómica, lípidomica y genómica se han multiplicado los avances en el diag nóstico y permiten explorar nuevas opciones terapéu ticas. Se ha establecido una nueva clasificación de los EIM en base a los más de 1.450 EIM identificados. Está irrumpiendo una nueva especialidad, que es la medici na metabólica. El cribado neonatal se estáempezando a universalizar y nos permite hoy en día, con tándem masas, el diagnóstico de más de 20 enfermedades me tabólicas del período neonatal que tienen opciones de tratamiento. Se están creando unidades de EIM para adultos para seguir niños con EIM que sobreviven a la enfermedad y con cada vez mejor calidad de vida y se diagnostican EIM que debutan en la adolescencia o laedad adulta. Aparecen las terapias personalizadas y las guías de práctica clínica para muchos EIM. Finalmente están emergiendo cada vez nuevas opciones terapéuticas que permiten una mayor supervivencia y mejor calidad de vida. La terapia génica convencional ya se está aplicando en algunos EIM.Sin embargo, las estrategias de edición de genes con terapias de ARN pueden permitir corregir la mutación genética mini mizando los problemas asociados con la terapia génica de compensación convencional.

Abstract The advances in the field of inborn errors of metabo lism (IEM) are spectacular. New IEM have been described, their pathophysiological bases and implications for the organism are better known. With the advent of new metabolomics, lipidomics and genomics techniques, advances in diagnosis have multiplied and allow new therapeutic options to be explored. A new IEM classi fication has been established based on the more than 1.450 IEM identified. A new specialty is emerging, which is metabolic medicine. Neonatal screening is becom ing universal and allows us today, with tandem mass, to diagnose more than 20 metabolic diseases of the neonatal period, with treatment options. IEM units for adults are being created to follow-up children with IEM who survive the disease and with an increasingly better quality of life, and some IEM that start in adolescence or adulthood are diagnosed. Personalized therapies and clinical practice guidelines appear for any IEM. Finally, new therapeutic options are emerging day to day that allow a longer survival and better quality of life. Con ventional gene therapy is already being applied in some IEM. However, gene editing strategies with RNA thera pies may allow the correction of the genetic mutation, minimizing the problems associated with conventional compensation gene therapy.

Biochemical and molecular characteristics of Malaysian patients with lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is an inborn error of dibasic amino acid transport due to a defect in the dibasic amino acid transporter in the renal and intestine and has a heterogenous presentation. Three Malaysian patients with LPI were studied and their biochemical and molecular findings compared. There were differences and similarities in the biochemical and molecular findings. Molecular analysis of SLC7A7 gene revealed a novel mutation c.235G>A; p.(Gly79Arg) in exon three in Patient 1 and a mutation c.1417C>T; p.(Arg473*) in exon 10 in patient 2 and 3. The degree of concentration of dibasic amino acids may determine the type of disease of the cell membrane transport, however, a positive molecular confirmation will secure the diagnosis.

The relationship between gastroesophageal reflux disease and idiopathic pulmonary interstitial fibrosis / 中华内科杂志

Objective To determine the prevalence of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary interstitial fibrosis (IPIF). Methods From December 2006 to January 2008, 24 consecutive patients with IPIF admitted to Beijing Chaoyang Hospital underwent 24-hour esophageal pH monitoring and esophageal manometry. Meanwhile, 23 patients with diffuse parenchymal lung disease (DPLD) (excluding IPIF) admired to the hospital in the same period served as a control group. Comparison of the prevalence of pathologic esophageal acid exposure GERD symptoms, and ineffective esophageal motility (IEM) between the two groups was made. In this study, nocturnal acid exposure is defined as acid reflux episodes occurring from 10pro to 6am. Results (1) 16 out of the 24 (66. 7%) patients with IPIF were demonstrated to have pathologic esophageal acid exposure; the prevalence of GERD in IPIF patients was significantly higher than that in other DPLD patients, whose prevalence was 26. 1% (P<0.05); (2) 87.5% patients with IPIF and GERD (GERD-IPIF) had nocturnal acid exposure episodes; (3) only 37.5% of the GERD-IPIF patients was found to have typical GERD symptoms such as heartburn and regurgitation; (4) The prevalence of IEM was similar in IPIF and other DPLD patients, being 42.9% and 39. 1% respectively (P >0. 05). Conclusions IPIF patients have higher prevalence of GERD and most of them usually do not show typical reflux symptoms. It is hereby suggested that IPIF patients should be screened with pH monitoring for GERD.

A Pre-embedding Technique of Nanogold-Silver Staining for Immunocytochemical Localization of Gp100 in Cultured Melanocytes / 대한해부학회지

Nanogold-silver staining is a pre-embedding immunocytochemical technique, making it possible to label antigens with particulate markers at the electron microscopic level. This technique is based on the advancement of gold technology and on the development of silver staining or enhancement. In the present study, the method of Nanogoldsilver staining that includes the use of high concentration of glutaraldehyde and gold toning as well, was used to localize gp100 or a membrane bound antigen in melanosome of the cultured melanocytes. With the HMB45 antibody against gp100, biotinylated secondary antibody and streptavidin-nanogold followed by silver enhancement and gold toning led to highly specific labeling of gold particle over the melanosome compartments. The specificity of labelings obtained with this protocol was confirmed by the control experiment. Omission of the primary antibody led to very low background of labeling. The specific signal that appeared as a collection of gold particles was localized mainly to the peripheral part of melanosome. This finding provides the more detailed nature of gp100 localization in melanosome, which has not yet been shown by the previous immunocytochemical study such as the post-embedding immunoelectron microscopy.