Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America.

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotypephenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:16561664, 2012. (c) 2012 Wiley Periodicals, Inc.

Liver transplantation and expanded Milan criteria: does it really work?

CONTEXT: Orthotopic liver transplantation is an excellent treatment approach for hepatocellular carcinoma in well-selected candidates. Nowadays some institutions tend to Expand the Milan Criteria including tumor with more than 5 cm and also associate with multiple tumors none larger than 3 cm in order to benefit more patients with the orthotopic liver transplantation. METHODS: The data collected were based on the online database PubMED. The key words applied on the search were "expanded Milan criteria" limited to the period from 2000 to 2009. We excluded 19 papers due to: irrelevance of the subject, lack of information and incompatibility of the language (English only). We compiled patient survival and tumor recurrence free rate from 1 to 5-years in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation according to expanded the Milan criteria from different centers. RESULTS: Review compiled data from 23 articles. Fourteen different criteria were found and they are also described in detail, however the University of California - San Francisco was the most studied one among them. CONCLUSION: Expanded the Milan criteria is a useful attempt for widening the preexistent protocol for patients with hepatocellular carcinoma in waiting-list for orthotopic liver transplantation. However there is no significant difference in patient survival rate and tumor recurrence free rate from those patients that followed the Milan criteria.