RESUMEN
BACKGROUND: Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. METHODS: We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. RESULTS: The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. CONCLUSIONS: Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.
Asunto(s)
Hemoglobinopatías/genética , Hemoglobinas/análisis , Hemoglobinas/genética , Adulto , Anciano de 80 o más Años , Preescolar , Cromatografía Líquida de Alta Presión , Pruebas Hematológicas , Hemoglobinopatías/sangre , Hemoglobinas/química , Humanos , Lactante , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: Hereditary anemia (HA) encloses a wide group of rare inherited disorders with clinical and hematologic overlaps that complicate diagnosis. MATERIALS AND METHODS: A 48-gene panel was developed to diagnose HA by Next Generation Sequencing (NGS) in a large cohort of 165 patients from 160 unrelated families. RESULTS: Patients were divided in: A) patients who had a suspicion of a specific type of HA (n = 109), and B) patients who had a suspicion of HA but with no clear type (n = 56). Diagnostic performance was 83.5% in group A and a change of the initial diagnosis occurred in 11% of these patients. In group B, 35.7% of patients achieved a genetic diagnosis. NGS identified 6 cases of xerocytosis, 6 of pyruvate kinase (PK) deficiency, 4 of G6PD, and 1 case of phytosterolemia with no initial suspicion of these pathologies, which is clinically relevant since they have specific treatment. Five patients were found to carry variants associated to two different pathologies (4 of them combining a metabolic deficiency and a membrane defect), and 44 new variants were identified in 41 patients. CONCLUSION: The use of NGS is a sensitive technique to diagnose HA and it shows better performance when patients are better characterized.
Asunto(s)
Anemia Hemolítica Congénita no Esferocítica , Anemia Hemolítica Congénita , Errores Innatos del Metabolismo del Piruvato , Anemia Hemolítica Congénita/diagnóstico , Anemia Hemolítica Congénita/genética , Anemia Hemolítica Congénita no Esferocítica/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato/diagnóstico , Errores Innatos del Metabolismo del Piruvato/genéticaRESUMEN
OBJECTIVES: The aim of the study was to investigate hemoglobin (Hb) species in a 61 year-old male with diabetes mellitus type II and a low value of Hb A(1c). DESIGN AND METHODS: Hb species were analyzed by electrophoresis and chromatography methods. Functional properties were determined by oxygen equilibrium studies. ß-globin gene was amplified by PCR and sequenced. RESULTS AND CONCLUSIONS: A novel clinically silent Hb (Hb Seville), that results in falsely low Hb A(1c) measurement, was detected. This Hb variant presented a single base mutation at codon 81 (CâT) of the ß-globin gene. This case points out the necessity of careful inspection of the chromatograms and the use of additional methods to Hb A(1c) measurement when the presence of aberrant peaks is detected.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía por Intercambio Iónico/métodos , Hemoglobina Glucada/análisis , Hemoglobinas Anormales/genética , Mutación/genética , Cromatografía de Fase Inversa , Hemoglobina Glucada/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , FenotipoAsunto(s)
Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/análisis , Hemoglobinas Anormales/análisis , Adulto , Anciano , Sustitución de Aminoácidos , Cromatografía/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Electroforesis Capilar , Reacciones Falso Negativas , Reacciones Falso Positivas , Glutamina/genética , Hemoglobinas Anormales/genética , Humanos , Lisina/genética , MasculinoRESUMEN
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