RESUMEN
Background: The 1-min sit-to-stand test (1STST) is a practical tool to evaluate physical capacity. The aim of this study was to assess the impact of tezacaftor and ivacaftor on functional exercise capacity, muscle strength and symptoms in people with cystic fibrosis (PwCF). Methods: The assessments were performed during the first year of tezacaftor and ivacaftor using the 1STST, 6-min walk test (6MWT), MicroFET2 dynamometer®, CF Questionnaire-Revised (CFQ-R), Leicester Cough Questionnaire (LCQ). Forced expiratory volume in 1 s (FEV1), body mass index (BMI), pancreatic sufficiency status, genotype and microbiologic data were also collected. Results: Fifty-four PwCF participated to the study and took at least one dose of tezacaftor-ivacaftor. Mean age was 26y±10 (±SD), median BMI 20.9 kg/m2 (interquartile range) (19.4; 23.5) and mean FEV1 82 percent of predicted values (%PV) ± 21. Significant correlations were found at baseline between the 1STST and the 6MWT (r = 0.617, p < 0.0001), the quadriceps strength (r = 0.6556, p < 0.0001) and the FEV1 (r = 0.29, p = 0.03). After one year of treatment, the 1STST increased significantly in terms of number of repetitions (n) (median 50 versus 58.5, p < 0.0001), %PV (101.1 versus 115.2%PV, p = 0.0003) and n times weight in kg (2885 versus 3389nxkg, p < 0.0001). The 6MWT distance and quadriceps strength were not modified after treatment but during the 6MWT, oxygen desaturation decreased significantly. FEV1, BMI, CFQ-R, LCQ improved as previously demonstrated. Conclusion: After one year of tezacaftor and ivacaftor, the 1STST improves, suggesting that the 1STST seems more responsive than the 6MWT and the MicroFET2 dynamometer® to assess the effects of CFTR modulators.
RESUMEN
Epstein-Barr virus-associated smooth pulmonary tumor is a rare condition that mostly affects immunosuppressed patients. This case describes a young boy with a history of kidney transplantation who presented recurrent pneumonia. Multiple endobronchial soft tissue tumors affecting both right and left bronchial tree were found and partially removed by bronchoscopy. Immunohistologic analysis demonstrated Epstein-Barr virus-associated smooth pulmonary tumor. Immunosuppressive therapy was changed from tacrolimus to sirolimus. A few months later, new right upper lobe and inferior left lobe tumors were found. Recurrent left lower lobe pneumonia prompted lobectomy. In the present case, complete resection and change of immunosuppressive treatment were effective.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Pulmonares/patología , Preescolar , Infecciones por Virus de Epstein-Barr/microbiología , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/microbiología , Masculino , PronósticoRESUMEN
INTRODUCTION/AIMS: Oropharyngeal dysphagia is common in patients with neuromuscular diseases (NMDs). Its early recognition is vital for proper management. We tested a large cohort of adult NMD patients for oropharyngeal dysphagia using the Sydney Swallow Questionnaire (SSQ). We also looked for possible differences in characteristics of oropharyngeal dysphagia in various NMD groups and diseases. Finally, we compared results of this screening with those from their corresponding medical records for eventual "clinical history" of dysphagia. METHODS: We asked patients to fill in the SSQ during follow-up outpatient visits at our neuromuscular reference center. A total score above the cutoff score of 118.5 out of 1700 was indicative of oropharyngeal dysphagia. RESULTS: Of the 304 adult patients assessed for eligibility, 201 NMD patients (96 women and 105 men, aged 49.0 ± 16.2 years) were included and tested in this study. Oropharyngeal dysphagia was detected in 45% of all the NMD patients when using the SSQ, whereas only 12% had a positive medical record for dysphagia. The median SSQ scores for patients with myotonic syndromes (including myotonic dystrophy type 1), with amyotrophic lateral sclerosis, and with facioscapulohumeral dystrophy were above the cutoff score. The SSQ scores obtained revealed distinct oropharyngeal dysphagia characteristics in the different NMD groups and diseases. DISCUSSION: The SSQ tests positively for oropharyngeal dysphagia in a higher proportion of NMD patients compared with their medical records. The distinct oropharyngeal dysphagia characteristics we revealed in different NMD groups and diseases may help to elaborate adapted clinical approaches in the management of oropharyngeal dysphagia.
Asunto(s)
Trastornos de Deglución/diagnóstico , Deglución/fisiología , Enfermedades Neuromusculares/complicaciones , Adulto , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Enfermedades Neuromusculares/fisiopatología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
Abnormal connections between the esophagus and low respiratory tract can result from embryological defects in foregut development. Beyond well-known malformations, including tracheo-esophageal fistula and laryngo-tracheo-esophageal cleft, rarer anomalies have also been reported, including communicating bronchopulmonary foregut malformations and tracheal atresia. Herein, we describe a case of what we have called "esophageal trachea," which, to our knowledge, has yet to be reported. A full-term neonate was born in our institution presenting with a foregut malformation involving both the middle esophagus and the distal trachea, which were found to be longitudinally merged into a common segment, 3 cm in length, located just above the carina and consisted of esophageal tissue without cartilaginous rings. At birth, the esophagus and trachea were surgically separated via right thoracotomy, the common segment kept on the tracheal side only, creating a residual long-gap esophageal atresia. The resulting severe tracheomalacia was treated via simultaneous posterior splinting of such diseased segment using an autologous pericardium patch, as well as by anterior aortopexy. Terminal esophagostomy and gastrostomy were created at that stage due to the long distance between esophageal segments. Between ages 18 and 24 months, the patient underwent native esophageal reconstruction using a multistage traction-and-growth surgical strategy that combined Kimura extra-thoracic esophageal elongations at the upper esophagus and Foker external traction at the distal esophagus. Ten months after esophageal reconstruction, prolonged, refractory, and severe tracheomalacia was further treated via anterior external stenting using a semitubular ringed Gore-Tex® prosthesis, through simultaneous median sternotomy and tracheoscopy. Currently, 2 years after the last surgery, respiratory stabilization, and full oral feeding were stably achieved. Multidisciplinary management was crucial for assuring lifesaving procedures, correctly assessing anatomy, and planning for multiple sequential surgical approaches that aimed to restore long-term respiratory and digestive functions.
Asunto(s)
Fibrosis Quística , Niño , Humanos , Pulmón/diagnóstico por imagen , Pruebas de Función RespiratoriaRESUMEN
The Pediatric Sleep Questionnaire described by Chervin et al. (Sleep Medicine, 2000, 1, 21-32) was originally validated for children with obstructive sleep apnoea syndrome but without other disorders. The aim of our study was to check the applicability of this questionnaire in children with underlying chronic medical conditions. Children aged 2-18â years who underwent a diagnostic sleep study at Great Ormond Street Hospital were recruited over a 10-month period. The Pediatric Sleep Questionnaire completed by their parents and cardiorespiratory polygraphy were scored. Sensitivities and specificities of the Pediatric Sleep Questionnaire were calculated using a Pediatric Sleep Questionnaire score of 0.33 as being indicative of sleep-disordered breathing. A total of 561 patients were reviewed. Neuromuscular disorders (nâ =â 108), craniofacial anomalies (nâ =â 58) and the obstructive sleep apnea syndrome control group (nâ =â 155) were best represented. The sensitivity for patients with isolated obstructive sleep apnoea syndrome was 76.5% when using an apnoea-hypopnoea index ≥â 5, but this was much lower when looking at specific sub-groups such as neuromuscular patients (25%) or patients with Trisomy 21 (36.7%). Sensitivities remained unchanged for patients with obstructive sleep apnoea syndrome (77.3%) when an apnoea-hypopnoea index of ≥â 1 was used, but improved for neuromuscular disorders sub-groups (36.7%) and Trisomy 21 (84%). In conclusion, the Pediatric Sleep Questionnaire is not a good screening tool for obstructive sleep apnoea syndrome in children with complex underlying disorders when a cut-off apnoea-hypopnoea index of ≥â 5 is used, and it cannot replace cardiorespiratory polygraphy recording.
Asunto(s)
Polisomnografía/métodos , Síndromes de la Apnea del Sueño/fisiopatología , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Tamizaje Masivo , Encuestas y CuestionariosRESUMEN
Congenital heart disease (CHD) is a common chronic disease. This study aimed to verify the relationship between spirometry and exercise capacity in children, considering the CHD severity. All cardiopulmonary exercise testing (CPET) and Spirometry from CHD children (5-18 years) were retrospectively reviewed during three years. CPET and Spirometry were analyzed and correlated based on the CHD severity[modified Ross classification (mR)]. Patients (n = 321) were analyzed and subdivided for CHD severity (n = 49, n = 149, n = 80, n = 43, from mR1 to mR4, respectively). The maximal workload (Wmax) in mR1 and mR2 was higher than in patients from mR3 and mR4. Peak oxygen uptake (peak VO2) was reduced in mR3 and mR4 compared to mR1 and mR2. Carbon dioxide output was only significantly lower in mR4. Although spirometric parameters were globally in the normal range, forced expiratory volume and forced vital capacity were different between subgroups (p < 0.001 and p = 0.002, respectively). Wmax and peakVO2 were weakly or moderately but significantly correlated with spirometry. Respiratory exchange ratio and final blood oxygen saturation were only significantly and weakly correlated to obstruction in small airways. The most severe CHD patients had lower exercise capacity and lung function parameters. A weak to moderate correlation between CPET and spirometry was found. However, the lung function reported in our study was normal, but with a negative correlation with the age. It reinforces the benefits of precocious and regularly spirometry and CPET assessment in CHD children.
Asunto(s)
Prueba de Esfuerzo/métodos , Tolerancia al Ejercicio/fisiología , Cardiopatías Congénitas/fisiopatología , Espirometría/métodos , Adolescente , Niño , Preescolar , Ejercicio Físico/fisiología , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this systematic review was to summarize the different dysphagia screening and evaluation tools, and to identify their measurement properties in adults with neuromuscular diseases (NMDs). METHODS: A systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was conducted across three databases (PubMed, CINAHL and ScienceDirect). Measurement properties of each tools and the Quality Index, developed by Downs and Black, were considered for the different investigated studies. RESULTS: The search strategy produced 2221 articles. After removal of duplicates and full-text analysis, 19 studies were included. Most of the publications focused on amyotrophic lateral sclerosis (ALS; n = 10) and Duchenne muscular dystrophy (DMD; n = 4). A total of 12 tools, listed as instrumental and noninstrumental examinations, were retrieved. A total of five of them used videofluoroscopic swallow study (VFSS). Measurement properties of the tools are not completely described in detail in many studies. The neuromuscular disease swallowing status scale, a noninstrumental tool, is the only one that assessed all measurement properties in ALS patients. The median score reported for the Quality Index was 16. CONCLUSIONS: This systematic review identified 12 different tools for the screening and evaluation of dysphagia in adults with NMD. Majority of the studies presented VFSS as a valid and reliable examination to assess dysphagia in ALS and DMD. Other tools were mainly evaluated in ALS patients, but further studies are needed to complete their measurement properties. In other NMDs, no firm conclusion can be made because of insufficient data and heterogeneity of NMDs.
RESUMEN
Oropharyngeal dysphagia is frequently under-reported and early detection may lead to adapt strategies of rehabilitation and management decisions. The Sydney Swallow Questionnaire (SSQ), a self-reported questionnaire for the detection and quantification of oropharyngeal dysphagia, was previously adapted and validated in other languages but not in French. The purposes of this study were to develop and validate a French version of SSQ (SSQ-f) and to assess its psychometric properties. This SSQ-f, obtained by back-translation and cross-cultural adaptation, was validated in 27 patients with impaired swallowing and 27 healthy controls. After inclusion, patients filled in the SSQ-f and performed a videofluoroscopic swallow study. The penetration aspiration scale (PAS) and Dysphagia outcome and severity scale (DOSS) were assigned to assess construct validity. Sensitivity and specificity of cut-off scores for the SSQ-f were assessed by the receiver operating characteristic (ROC) curves. Moreover, the SSQ-f was repeated after 2 weeks to evaluate its test-retest reliability. The results supported that SSQ-f was considered understandable. Its total score was strongly correlated to the DOSS (r = - 0.873) and to the PAS (r = 0.738). It demonstrated acceptable internal consistency, with Cronbach's alpha values ranging from 0.744 to 0.956. The test-retest reliability was excellent. According to the ROC curve, cut-off scores of 118.5 or 218.5 were proposed for determining oropharyngeal dysphagia using DOSS as a reference and 755.0, using PAS as reference. No ceiling or floor effects were observed. In conclusion, the SSQ-f is a valid and reliable instrument to measure and detect oropharyngeal dysphagia in French-speaking subjects and can be used in a clinical setting.
Asunto(s)
Trastornos de Deglución/diagnóstico , Cultura , Deglución , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , TraducciónRESUMEN
AIM: Dysphagia is frequent in paediatric patients with neuromuscular diseases (pNMD). Its detection is important for initiating early diagnosis and treatment as well as for minimizing related complications. The aim of this study was to review the literature on dysphagia screening and evaluation tools in pNMD. METHOD: A systematic review was performed on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (PubMed, CINAHL, and ScienceDirect) were searched. Measurement properties of tools and the quality index developed by Downs and Black were considered. RESULTS: Our search yielded four studies and four different tools for paediatric patients with Duchenne muscular dystrophy (DMD). The Sydney Swallow Questionnaire, surface electromyography, Neuromuscular Disease Swallowing Status Scale, and videofluoroscopic swallow study showed interesting properties for DMD. No data were available for other NMD and children under 9 years. The mean total score for the quality index was 17.5. INTERPRETATION: We did not identify any superior validated tools, either for screening or for evaluation of dysphagia, and no widely accepted protocol. Further studies are needed to identify the simplest assessment with the best psychometric properties for pNMD. We recommend establishing a specific tool for pNMD.
Asunto(s)
Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Enfermedades Neuromusculares/complicaciones , Niño , HumanosRESUMEN
BACKGROUND: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. METHODS: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. RESULTS: In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p < 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations. CONCLUSIONS: Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trials.
Asunto(s)
Hemiplejía/genética , Mutación , ATPasa Intercambiadora de Sodio-Potasio/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Encuestas Epidemiológicas , Hemiplejía/diagnóstico , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
Platelets, known for their role in primary haemostasis, prevent excessive bleeding after injury. The study of platelets has, therefore, traditionally focused on bleeding disorders. It has recently become evident, however, that platelet research can contribute to unravelling the disease mechanisms that underlie neuropathological disorders that have a subtle subclinical platelet phenotype. Platelets and neurosecretory cells have common gene expression profiles and share several biological features. This review provides a literature update on the use of platelets as easily accessible cells to study neurological disorders. We provide examples of the use of different platelet-based tests to understand the underlying pathophysiological mechanisms for both complex and monogenetic neuropathological disorders. In addition to the well-studied regulated granule secretion and serotonin metabolism, more recent studies have shown that defects in transcription factors, membrane transporters, G-protein signal transduction, and cytoskeletal proteins can be investigated using platelets to gain information on their role in neuropathology.
Asunto(s)
Plaquetas/fisiología , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/genética , Plaquetas/metabolismo , Humanos , Enfermedades del Sistema Nervioso/patologíaRESUMEN
Alternating hemiplegia of childhood (AHC) is a rare syndrome with repeated hemiplegic episodes, paroxysmal events and global neurological impairment. Recently, heterozygous de novo ATP1A3 missense mutations have been identified in AHC patients, but the underlying pathogenesis mechanism remains unknown. Mutation analysis of ATP1A3 in 9 unrelated AHC cases revealed mostly D801N or E815K variants. As platelets represent a good cellular model to study defects in neuropathologies, morphological and functional experiments were performed in these subjects. Platelets from the AHC patients presented with structural and functional abnormalities of granules positive for the lysosomal marker CD63. Similar structural granule abnormalities were detected in patients' fibroblasts. Proteomic analysis of platelets and fibroblasts showed a total of 93 differentially expressed proteins in AHC mainly involved in metabolism. Interestingly, 7 of these proteins were detected in both cell types, including the lysosomal protein cathepsin. AHC fibroblasts revealed significantly increased levels of activated cathepsin B, which induces a stronger activation of apoptosis. Our study is the first to link ATP1A3 defects in AHC to a platelet and fibroblast lysosomal defect with evidence of increased apoptosis. Further studies are needed to define how this lysosomal defect is related to decreased ATPase activity. Biological Significance Only recently, the genetic cause of AHC was identified as heterozygous ATP1A3 mutations, but the underlying pathophysiological mechanism still remains unknown. By performing functional, morphological and proteomic studies in AHC patients we found a structural and functional granule defect in AHC platelets and fibroblasts that was specifically found in granules positive for the lysosomal marker CD63. In particular, proteomics identified several differentially expressed proteins in fibroblasts and platelets from AHC cases that are predicted to have an important role in cell function and maintenance, a pathway typically attributed to lysosomes. The lysosomal protein cathepsin was found to be differentially expressed in both platelets and fibroblasts of AHC patients, inducing a stronger activation of mainly the intrinsic apoptosis. Despite the precise mechanism for the increased lysosomal cathepsin B-dependent apoptosis detected in AHC in relation to impaired ATP1A3 deserves further studies, we could here show some evidence for a defective regulation of apoptosis in AHC, a disease that still has no biochemical or neuroradiological parameters for diagnosis.
Asunto(s)
Plaquetas/metabolismo , Catepsina B/metabolismo , Hemiplejía/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Apoptosis/genética , Catepsina B/genética , Electroforesis en Gel Bidimensional , Femenino , Fibroblastos/metabolismo , Hemiplejía/metabolismo , Hemiplejía/patología , Humanos , Lactante , Recién Nacido , Lisosomas/enzimología , Masculino , TranscriptomaRESUMEN
The Forkhead box G1 (FOXG1) gene encodes a transcriptional repressor essential for early development of the telencephalon. Intragenic mutations and gene deletions leading to haploinsufficiency cause the congenital variant of Rett syndrome. We here describe Rett syndrome-like patients, three of them carrying a balanced translocation with breakpoint in the chromosome 14q12 region, and one patient having a 14q12 microdeletion excluding the FOXG1 gene. The hypothesis of long-range FOXG1-regulatory elements in this region was supported by our finding of reduced FOXG1 mRNA and protein levels in platelets and skin fibroblasts from these cases. Given that FOXG1 is not only expressed in brain but also in platelets, we have studied platelet morphology in these patients and two additional patients with FOXG1 mutations. Electron microscopy of their platelets showed some enlarged, rounder platelets with often abnormal alpha, and fewer dense granules. Platelet function studies were possible in one 14q12 translocation patient with a prolonged Ivy bleeding time and a patient with a heterozygous FOXG1 c.1248C>G mutation (p.Tyr416X). Both have a prolonged PFA-100 occlusion time with collagen and epinephrine and reduced aggregation responses to low dose of ADP and epinephrine. Dense granule ATP secretion was normal for strong agonists but absent for epinephrine. In conclusion, our study shows that by using platelets functional evidence of cis-regulatory elements in the 14q12 region result in reduced FOXG1 levels in patients' platelets having translocations or deletions in that region. These platelet functional abnormalities deserve further investigation regarding a non-transcriptional regulatory role for FOXG1 in these anucleated cells.
Asunto(s)
Plaquetas/metabolismo , Cromosomas Humanos Par 14/genética , Factores de Transcripción Forkhead/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Síndrome de Rett/genética , Translocación Genética/genética , Adulto , Encéfalo/metabolismo , Niño , Femenino , Fibroblastos/metabolismo , Factores de Transcripción Forkhead/metabolismo , Humanos , Masculino , Proteínas del Tejido Nervioso/metabolismo , Síndrome de Rett/metabolismo , Piel/metabolismoRESUMEN
PURPOSE: Aquaporin 7 (AQP7) belongs to the aquaglyceroporin family, which transports glycerol and water. AQP7-deficient mice develop obesity, insulin resistance, and hyperglyceroluria. However, AQP7's pathophysiologic role in humans is not yet known. METHODS: Three children with psychomotor retardation and hyperglyceroluria were screened for AQP7 mutations. The children were from unrelated families. Urine and plasma glycerol levels were measured using a three-step enzymatic approach. Platelet morphology and function were studied using electron microscopy, aggregations, and adenosine triphosphate (ATP) secretion tests. RESULTS: The index patients were homozygous for AQP7 G264V, which has previously been shown to inhibit transport of glycerol in Xenopus oocytes. We also detected a subclinical platelet secretion defect with reduced ATP secretion, and the absence of a secondary aggregation wave after epinephrine stimulation. Electron microscopy revealed round platelets with centrally located granules. Immunostaining showed AQP7 colocalization, with dense granules that seemed to be released after strong platelet activation. Healthy relatives of these patients, who were homozygous (not heterozygous) for G264V, also had hyperglyceroluria and platelet granule abnormalities. CONCLUSION: The discovery of an association between urine glycerol loss and a platelet secretion defect is a novel one, and our findings imply the involvement of AQPs in platelet secretion. Additional studies are needed to define whether AQP7 G264V is also a risk factor for mental disability.
Asunto(s)
Acuaporinas/genética , Trastornos de las Plaquetas Sanguíneas/genética , Homocigoto , Mutación , Adolescente , Adulto , Sustitución de Aminoácidos , Acuaporina 3/genética , Acuaporinas/metabolismo , Plaquetas/metabolismo , Plaquetas/ultraestructura , Niño , Preescolar , Codón , Femenino , Glicerol/sangre , Glicerol/orina , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , Transporte de Proteínas , Adulto JovenRESUMEN
Platelet function in primary hemostasis involves the secretion of granules upon activation, providing the localized delivery of effector proteins at sites of vascular injury. The sequential process of regulated secretion in platelets, from the biogenesis of the granules, through their transport and up to the exocytotic fusion process at the acceptor membrane, involves a complex molecular machinery conserved between some other specialized cells such as neurons. Mutations in genes encoding proteins involved in this process of granule trafficking have helped towards demystification of the underlying secretory mechanisms. Human diseases of trafficking encompass a broad symptomatology including a platelet-related bleeding diathesis and neuronal problems. In this review, we want to highlight the similarities in granule biology between platelets and neurons and further focus on some granule trafficking disorders that result in bleeding and neuropathology. This review provides evidence that platelet research can be expanded from traditional studies of isolated thrombopathies to the field of neuropathologies that include a platelet secretion defect.