Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias: Experience of the Spanish Network on Bone Marrow Failure Syndromes.

Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders.

Identificación de infradiagnóstico de enfermedad renal crónica en Atención Primaria / Underdiagnosis identification of chronic kidney disease in primary care

Introducción: La enfermedad renal crónica afecta a un 9,16% de la población española. Su elevada prevalencia e infradiagnóstico requieren de coordinación interdisciplinar para mejorar la prevención, diagnóstico y tratamiento de esta patología. Así, nos planteamos identificar la prevalencia real de enfermedad renal crónica en nuestra Área Básica de Salud, detectando errores de codificación y diagnóstico. Material y Método: Estudio observacional transversal en pacientes mayores de 14 años pertenecientes al Área Básica de Salud de Balaguer. Los criterios de clasificación diagnóstica fueron: pacientes diagnosticados de enfermedad renal crónica o no codificados con alteración renal medida por filtrado glomerular, cociente albúmina/creatinina o albuminuria leve. Se consideraron como pérdidas los exitus y los pacientes con cambio de área básica de salud. Las variables estudiadas fueron: diagnóstico y estadio de enfermedad renal crónica, albuminuria leve, cociente albúmina/creatinina, filtrado glomerular y determinaciones analíticas. Se realizó una codificación a través de la revisión de la historia clínica. El análisis se basó en prevalencias. Resultados: La prevalencia aumentó del 3,98% inicial al 6,00% tras la revisión. Manteniéndose aún cifras de infradiagnóstico, con una detección de dos terceras partes de lo esperado. Añadiendo los pacientes pendientes de una segunda determinación analítica y los que padecen albuminuria leve, la prevalencia representaba el 80% de lo esperado (7,40%). Conclusiones: Se observa la existencia de infradiagnóstico en la detección precoz de ERC. Una revisión de los criterios de clasificación ayudan a mejorar las cifras de este infradiagnóstico

Introduction: Chronic kidney disease affects 9.16% of the Spanish population. The high prevalence and underdiagnosis require interdisciplinary coordination to improve the prevention, diagnosis and treatment of this pathology. Thus, we propose to identify the real prevalence of chronic kidney disease in our Basic Health Area, to detect coding and diagnostic errors, and to increase detection. Material and Method: Cross-sectional observational study in patients older than 14 years residing in the Basic Health Area of Balaguer. The diagnostic classification criteria were patients diagnosed with chronic kidney disease or not coded with renal impairment, measured by glomerular filtration rate, albumin/creatinine ratio or mild albuminuria. Loss of follow-up were considered deaths and patients with change in Basic Health Area. The variables studied were: diagnosis and stage of chronic kidney disease, mild albuminuria, albumin/creatinine ratio, glomerular filtration and analytical determinations. A coding was performed through the review of the medical history. The analysis was based on prevalence. Results: The prevalence increased from an initial 3.98% to 6.00% after the review. Underdiagnosis figures were maintained, with a detection of two thirds of the expected. Adding the patients pending a second analytical determination and those suffering from mild albuminuria, the prevalence represented 80% of the expected (7.40%). Conclusion: The existence of underdiagnosis is observed in the early detection of CKD. A review of the classification criteria helps to improve underdiagnosis data