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Niemann-Pick disease type B (NPDB) is a rare, inherited lysosomal storage disorder that occurs due to variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene and the resultant deficiency of acid sphingomyelinase (ASM) activity. While numerous variants causing NPDB have been described, only a small number have been studied in any detail. Herein, we describe the frequency of the p.(Ala359Asp) variant in the healthy Chilean population, and determine the haplotype background of homozygous patients to establish if this variant originated from a common founder. Genomic DNA samples from 1691 healthy individuals were analyzed for the p.(Ala359Asp) variant. The frequency of p.(Ala359Asp) was found to be 1/105.7, predicting a disease incidence of 1/44 960 in Chile, higher than the incidence estimated by the number of confirmed NPDB cases. We also describe the clinical characteristics of 13 patients homozygous for p.(Ala359Asp) and all of them had moderate to severe NPDB disease. In addition, a conserved haplotype and shared 280 Kb region around the SMPD1 gene was observed in the patients analyzed, indicating that the variant originated from a common ancestor. The haplotype frequency and mitochondrial DNA analysis suggest an Amerindian origin for the variant. To assess the effect of the p.(Ala359Asp) variant, we transfected cells with the ASM-p.(Ala359Asp) cDNA and the activity was only 4.2% compared with the wild-type cDNA, definitively demonstrating the causative effect of the variant on ASM function. Information on common variants such as p. (Ala359Asp) is essential to guide the successful implementation for future therapies and benefit to patients.

General considerations, indications and contraindications for liver transplantation in Chile. A multicenter consensus development documentLiver transplantation is an excellent therapeutic option for terminal liver disease. During the last decades the results of liver transplantation have improved significantly with a patient survival rate of nearly 90% at one year and 80% at 5 years of follow-up. The main indications for liver transplantation include: end-stage liver disease associated to cirrhosis, acute liver failure, and hepatic tumors (mainly hepatocarcinoma). The absolute contraindications for a transplant are less frequent than in the past, and include: severe co-morbidity (cardiac or pulmonary), sepsis, advanced HIV disease and extra-hepatic malignancy. This document presents a Consensus of the main groups performing liver transplantation in Chile, about its indications and contraindications. It also reviews general aspects of liver transplantation, including the selection and referral of liver transplant candidates, allocation of organs and the evaluation of severity of liver disease (Rev Méd Chile 2008; 136: 793-804). (

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