Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry

\ua9 2023Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient\u27s journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country

Mutation spectrum in the large GTPase dynamin 2, and genotype–phenotype correlation in autosomal dominant centronuclear myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 ( DNM2 ), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM‐related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice‐site mutation. Genotype–phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot–Marie–Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue‐specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT. Hum Mutat 33:949–959, 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92087/1/22067_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92087/2/humu_22067_sm_SuppInfo.pd