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Introduction and Objectives: Pompe disease is a rare autosomal recessive disorder produced by a deficiency of acid maltase. This deficit produces an accumulation of glycogen in tissues. Clinically it is mainly characterized by limb girdle and respiratory muscle weakness. In 2013, we developed the Spanish Pompe Registry. The objective of this article was to analyse the characteristics of the first 49 patients and disclose the existence of this registry within the medical community., Material and Methods: An observational retrospective study was undertaken. We analysed the 49 patients included in the Spanish Registry of Pompe Disease from May 2013 to October 2018., Results: Patients were visited at 7 different Spanish hospitals. Twenty-six patients were women and 23 were men. The average age at the time of the analysis was 47.2 years. Ten patients were asymptomatic. The mean age of onset of symptoms was 29, and low limb girdle weakness was the most frequent initial symptom. Of the patients, 49% had respiratory involvement, and 70.8% of them required non-invasive mechanical ventilation. The most common mutation found was IVS1-13T>G in 85.3% of the patients. All symptomatic patients received treatment with ERT., Conclusions: This registry allows us to know the clinical and genetic characteristics of adult patients with Pompe disease in Spain. Moreover, it can be the basis for future studies of natural history to understand the impact of ERT in the course of the disease., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT.

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 × 10(-5)), and more family history of ALS (P = 1.4 × 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes., (© 2012 Wiley Periodicals, Inc.)