Infantile-onset Pompe disease in seven Mexican children.

INTRODUCTION: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. OBJECTIVE: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. METHODS: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. RESULTS: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. CONCLUSION: There was a good correlation between genotype and phenotype in children with Pompe disease.

INTRODUCCIÓN: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. OBJETIVO: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. MÉTODOS: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. RESULTADOS: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. CONCLUSIÓN: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

BACKGROUND: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients. METHODS: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency. RESULTS: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG). CONCLUSION: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.

Agreement of Mexican FRAX with and without the value of bone mineral density in assessing the risk of fracture in daily clinical practice. / Concordancia del FRAX México con y sin el valor de la densidad mineral ósea en la evaluación del riesgo de fractura en la práctica clínica diaria.

INTRODUCTION: The use of FRAX without the inclusion of bone mineral density (FRAX-BMI) may be useful in clinical practice to identify patients at high risk of fracture and inform treatment decisions, but its usefulness is debated. The aim of the study is to evaluate the agreement between the risk of fracture calculated by FRAX with or without bone mineral density (BMD). PATIENTS AND METHODS: A cross-sectional study was conducted with 431 women (40-90 years) without treatment. The concordance of the probability of fracture was assessed by the concordance correlation coefficient (CCC), and by Bland-Altman method. The kappa index was used to evaluate the agreement between treatment indications. RESULTS: The difference between the risks of a major osteoporosis fracture (MOFR) was 1.02±1.40% (95% CI -2 to 1.90) and -0.03±0.51% (95% CI -1.18 to 1.32) for the hip fracture risk (HFR). Agreement between MOFR and HFR FRAX scores was good (CCC 0.879, 95% CI 0.85-0.90 and CCC 0.821, 95% CI 0.79-0.85, respectively). The correlation between BMD of the femoral neck and fracture risk calculated by FRAX-BMI was a moderate, MOFR (r=-0.55, P<.001) and HFR (r=-0.54, P<.001). The agreement between the recommendations of treatment was 87% (kappa 0.61). CONCLUSIONS: The good agreement between the risk of fracture obtained suggests that FRAX-BMI allows us to provide an estimate of risk in most cases.

Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between self-rated clinimetric evaluation and clinical evaluation with activity indexes: DAS28, CDAI and SDAI. / Evaluación de la actividad de la artritis reumatoide en la atención clínica habitual. Concordancia entre la autoclinimetría y la evaluación clínica con los índices de actividad: DAS28, CDAI y SDAI.

INTRODUCTION AND OBJECTIVE: To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. PATIENTS AND METHOD: Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. RESULTS: The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). CONCLUSION: The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness.

Enfermedad de Pompe de inicio infantil en siete niños mexicanos / Infantile-onset Pompe disease in seven Mexican children

Resumen Introducción: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. Objetivo: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. Métodos: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. Resultados: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. Conclusión: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

Abstract Introduction: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. Objective: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. Methods: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. Results: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. Conclusion: There was a good correlation between genotype and phenotype in children with Pompe disease.

Gout and pregnancy: A report of a new case and systematic review / Gota y embarazo: revisión sistemática, incluyendo el reporte de un nuevo caso

Abstract Article history: Received 4 January 2017 Accepted 17 October 2017 Available online 24 May 2018 Introduction: Unlike other rheumatic diseases, gout is rare in women of childbearing age. Due to the low number of cases available for the study, current information is based mainly on case reports. Objective: To describe the characteristics and the outcome of the pregnancy of women with gout. Methods: A systematic literature search was undertaken by the investigators in the PubMed and Embase databases, from the inclusion date to August 2016. Patients were included if they met the definition of gout according to the American Rheumatism Association criteria, and that they had the description of its follow-up during the pregnancy. Data collection and analysis: each pregnancy was treated as a separate observation for analysis. The maternal and fetal-neonatal outcomes data were extracted from the articles finally selected. Results: The search identified 125 potentially relevant articles, but after a full-text review only 12 articles met the inclusion criteria. Of the 23 pregnancies described, there were 16 (69.5%) live births, 5 (21.7%) were aborted, in one (4.3%), the pregnancy was terminated, and in one case report (4.3%) there was no description on the term of pregnancy. No maternal deaths were reported. Two babies died a few hours after birth. Congenital malformations were not described in any case report. The most frequent maternal complications were renal damage, anemia, preeclampsia, and postpartum uremia. Conclusions: Gout during pregnancy is not common, but it is known to occur. While the majority of women with gout delivered healthy infants, they were at increased risk of having maternal complications.

Resumen Introducción: A diferencia de otras enfermedades reumáticas, la gota es una enfermedad rara en mujeres en edad fértil. Debido al escaso número de casos disponibles para el estudio, la información actual se basa, principalmente, en reportes de casos. Objetivo: Describir las características y el desarrollo del embarazo en mujeres con gota. Métodos: Una búsqueda sistemática de literatura fue realizada en las bases de datos PubMed, Lilacs, Ebsco y Embase, desde la fecha de inclusión hasta agosto del 2016. Se incluyó a pacientes que cumplieron con la definición de gota según los criterios de la American Rheumatism Association y que tenían la descripción de su seguimiento durante el embarazo. Cada embarazo se trató como una observación independiente para el análisis. A partir de los artículos finalmente seleccionados, se extrajeron los desenlaces materno-fetales. Resultados: La búsqueda identificó 125 artículos potencialmente relevantes, después de la revisión de texto completo, 12 artículos cumplieron los criterios de inclusión. Se describen 23 embarazos que resultaron en 16 (69,5%) nacimientos vivos, 5 (21,7%) abortos, una (4,3%) interrupción del embarazo y en un caso (4,3%) no se describió el desenlace. No se reportaron muertes maternas. Dos recién nacidos fallecieron después del parto. No se documentaron malformaciones congénitas. Las complicaciones maternas más frecuentes fueron la insuficiencia renal, la anemia, la preeclampsia y la uremia posparto. Conclusiones: La gota durante el embarazo no es común, pero se sabe que ocurre. Mientras que la mayoría de las mujeres con gota tuvieron bebés sanos, presentaban un mayor riesgo de tener complicaciones maternas.