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Summary: Morphoea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis and/or subcutaneous tissues. Intravenous IgG therapy has induced improvement in some fibrotic conditions. The primary indication for subcutaneous IgG (SCIG) is in primary immunodeficiency disorders as replacement therapy; however, recently there has been considerable interest in SCIG as an immunomodulatory agent. We report an 11‐year‐old girl with deep morphoea who was successfully treated with SCIG. [ABSTRACT FROM AUTHOR]

From July to December 2001 data were obtained from egg collections and releasing of hatched turtles at 21 conservation centers of Michoac´n State, México. The objective was to determine the hatching efficiency of collected eggs and the release of small turtles. The extracted eggs from their original nests were transported to protection centers and the recently hatched but dynamic turtles were liberated. Results show 700 thousand released turtles that comprised 78% of survival rate from the total eggs collected. The care of complete nests guarantees a higher clutching and survival rate of the young turtles. [ABSTRACT FROM AUTHOR]

After the approval of gene therapy treatment for spinal muscular atrophy (SMA) in 2021, more and more patients have benefited from this treatment so it is important to know the nationally treatment experience and evolution of these patients in real life outside clinical trials. know the current situation of SMA patients treated with gene therapy at national level through the CuidAME registry. Retrospective observational and multicenter study. We collected data on the treatment, safety and evolution of patients treated with gene therapy collected in the CuidAME registry from its approval to the present. Patients currently participating in clinical trials were excluded. There are currently registered a total of 33 patients treated with gene therapy in CuidAME, of which we were able to collect information from 25 who were included in this study. 84% were type 1 and 16% presymptomatic. 88% had 2 copies of SNM2 and 12% had 3 copies. The mean age at symptom onset was 1.9 months. At the present time 70% have reached sitting and 20% have reached standing. Gene therapy has changed the natural history of SMA 1 patients. Long-term follow-up is needed to better understand efficacy and safety in the real world, as well as characterization of new phenotypes in patients treated at early ages. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a genetic, neurodegenerative disease characterized by progressive muscle weakness and atrophy leading to disability and paralysis. Nusinersen is an SMN2 -directed antisense oligonucleotides (ASO) working by blocking splicing once they are bound to pre-mRNA, which allows exon 7 to be preferentially included and therefore produce more full-length SMN protein. Nusinersen is available since 2016 in USA and 2018 in Spain. The CUIDAME project is an observational Spanish SMA population database where clinical data are collected through a digital platform. Here we present a descriptive analysis of the cohort treated with Nusinersen included in the platform until April 2024. 146 and 106 pediatric and adult patients respectively had been treated with Nusinersen at the time of recruitment, representing the 66.6% and 43.3% of the pediatric and adult population. Regarding SMA type and treatment outcomes: 60 SMA1 pediatric patients had been treated with CHOP-ATEND score change from 19.3 at the beginning of the treatment to 47.9 in last measure; 58 SMA2 pediatric patients had been treated with CHOP-ATEND score change from 44.1 to 51.2 and HFMSE score change from 20 to 26.9; 26 SMA3 pediatric patients had been treated with CHOP-ATEND score change from 61 to 61.8 and HFMSE score change from 45.1 to 51.7. 29 SMA2 adult patients had been treated with HFMSE score change from 5 to 4.6 and EK2 score change from 20.3 to 18.8; 75 SMA3 adult patients had been treated with HFMSE score change from 36.4 to 34.9, EK2 score change from 10 to 6.3 and 6MWT score change from 282.5 to 388.2 meters. Just two pre-symptomatic patients had been treated with Nusinersen. Considering nutritional status, 54% of treated pediatric SMA1 require nutritional support, 18% of treated pediatric SMA2 and no pediatric SMA3. No adult SMA patient treated with Nusinersen requires nutritional support. Focusing on respiratory situation, 83.9% of treated pediatric SMA1 require any type of ventilation being just 11.1% invasive, 34.5% of treated pediatric SMA2 require ventilation being just 7% invasive and no treated pediatric SMA3 requires ventilation. 56% of treated adult SMA2 and 6% of treated adult SMA3 require ventilation, all of them non-invasive. In conclusion, both the pediatric and adult population included in the CUIDAME registry treated with Nusinersen show an improvement either in motor or functional scales. Regarding nutritional or respiratory implications, a high percentage of SMA2 require support of some kind, being lower in SMA3 and in the adult population. [ABSTRACT FROM AUTHOR]

Pompe 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's 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Purpose: MORC2 mutations have been described as a rare cause of axonal Charcot-Marie-Tooth disease (CMT2Z). The aim of this work was to determine the frequency and distribution of these mutations throughout Spain, to provide a comprehensive phenotypical description and, if possible, to establish a genotype-phenotype correlation., Methods: Retrospectively, data on patients diagnosed with CMT2Z in Spain were collected and clinical, electrophysiological and muscle imaging information were analysed., Results: Fifteen patients with CMT2Z were identified throughout Spain, seven of them belonging to a single kindred, whilst the rest were sporadic. The most common mutation was p.R252W, and four new mutations were identified. Eleven patients were categorized as having a scapuloperoneal phenotype, with asymmetric muscle weakness, early proximal upper limb involvement and frequent spontaneous muscular activity with distal sensory impairment and pes cavus, whilst two presented with a more classic length dependent sensory motor phenotype. This distinction was corroborated by the distribution of muscle fatty infiltration in muscle imaging. Two other patients were classified as having a neurodevelopmental phenotype consisting in congenital or early onset, delay in motor milestones, and global developmental delay in one of them. Nerve conduction studies revealed an unequivocally axonal neuropathy with frequent spontaneous activity, and serum creatine kinase levels were increased in 50% of the patients., Conclusions: MORC2 mutations are a rare cause of CMT in Spain, but in-depth phenotyping reveals a recognizable phenotypic spectrum that will be clinically relevant for future identification of this disease., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied., Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses' polymerase chain reaction were collected monthly, and between visits in case of symptoms., Results: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls ( p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls ( p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points ( p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts ( p < 0.05), particularly when these episodes were moderate/severe., Conclusions: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

Background: Autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only five cases have been reported with four distinct pathogenic mutations., Objectives: We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease's phenotype., Methods: This is a case report presentation of a 3-year-old boy, seen at a reference paediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs., Results: A 3-day-old boy presented to the emergency department with a vesiculo-pustular rash that resolved within 1 week. Two months later, he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhoea and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work-up showed mild neutropenia, decreased serum levels of immunoglobulins and B-cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leucocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG&#95;376t1:c.2543T>C or p.(Leu848Pro)]., Conclusions: Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient, suggesting that it could be a PLCG2 gene 'hot-spot'., (© 2019 European Academy of Dermatology and Venereology.)

Objective: Cost-minimization analysis of onabotulinumtoxinA and abobotulinumtoxinA, taking into account the real dose administered to children with spasticity associated with dynamic equinus foot deformity due to cerebral palsy., Method: A single centre, observational, longitudinal, and retrospective study which included spastic paediatric patients aged 2-to-18-years and treated with onabotulinumtoxinA or abobotulinumtoxinA from December 1995 to October 2012, in the Paediatric Neurology Unit of a first-level Spanish hospital. A longitudinal analysis of spasticity severity was made to confirm the similar efficacy of both treatments. Cost minimization was analyzed using the dose administered and the direct costs (pharmacological and medical visits costs) from the perspective of the National Health System (in euros from 2016)., Results: We analyzed 895 patients with paediatric spasticity: 543 were treated only with onabotulinumtoxinA, 292 only with abobotulinumtoxinA, and 60 with both treatments. The mean doses administered were 5.44 U/kg (SD = 2.17) for onabotulinumtoxinA, and 14.73 U/kg (5.26) for abobotulinumto xinA. The total annual direct cost (pharmacological and medical visits) was € 839.56 for onabotulinumtoxinA and € 631.23 for abobotulinumtoxinA, which represents a difference of € 208.34 per year in favour of treatment with abobotulinumtoxinA., Conclusions: It has been demonstrated that in real clinical practice, the cost per patient and year for treatment of paediatric spasticity was lower when abobotulinumtoxinA was used., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Onychomycosis is known to have predisposing factors and a high prevalence within families that cannot be explained by within-family transmission. We determined the frequency of HLA-B and HLA-DR haplotypes in 25 families of Mexican patients with onychomycosis in order to define the role of the class II major histocompatibility complex (MHC) in genetic susceptibility to this infection. Seventy-eight subjects participated in the study, 47 with onychomycosis and 31 healthy individuals. The frequencies of the HLA-B and HLA-DR haplotypes were compared with those found in first-degree relatives without onychomycosis and in a historic control group of healthy individuals. The frequencies in the controls were similar to those of the healthy relatives of the patients. However, on comparison of the patients with historic controls, we detected a higher frequency of the HLA-DR8 haplotype (P=.03; odds ratio, 1.89; 95% confidence interval, 0.98-36). These findings suggest that there are polymorphisms in genes of the MHC that increase susceptibility to onychomycosis, particularly haplotype HLA-DR8., (Copyright © 2010 Elsevier España, S.L. and AEDV. All rights reserved.)