Publication: Modelling and gene therapy for pyruvate kinase deficiency
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2019-05-23
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Universidad Complutense de Madrid
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Abstract
La deficiencia en piruvato quinasa (PKD, por sus siglas en inglés) es la principal causa de anemia hemolítica no esferocítica. Es una enfermedad monogénica-recesiva que se origina por mutaciones en el gen PKLR. Aunque este gen codifica la información para la producción de dos isoformas de piruvato quinasa, expresadas en hígado y en eritrocitos, solo el linaje eritroide se ve afectado. La piruvato quinasa es la enzima que cataliza la última reacción de la glicólisis, un proceso exergónico crucial para la supervivencia energética de los eritrocitos.Dada su baja prevalencia (alrededor de 5 de cada 20.000 habitantes), PKD es considerada una enfermedad rara. La severidad de la enfermedad es variable, desde casos leves con niveles de hemoglobina de 11 g/dL que solo necesitan transfusiones de eritrocitos puntuales durante exacerbaciones de la enfermedad, hasta casos graves con niveles de hemoglobina inferiores a 8.5 g/dL, dependientes de transfusiones periódicas que incluso pueden causar la muerte. Los casos más severos son dependientes de transfusiones periódicas incluso después de ser esplenectomizados, el tratamiento paliativo utilizado más agresivo...
Pyruvate kinase deficiency (PKD) is the main cause of chronic non-spherocytichemolytic anemia. This disease is a monogenic recessive disorder that occurs due to mutations in PKLR gene. Although this gene codifies the expression of two isoforms of pyruvate kinase, expressed in liver and in red blood cell s, only the erythroid lineage is affected. Pyruvate kinase is the enzyme that catalyzes the last step of the glycolysis, a critical exergonic reaction for the energetic survival of erythrocytes. Due to its low prevalence (about 5:20,000), PKD is considered a rare disease. Severity of the disease is variable, ranging from mild cases, having hemoglobin levels around11 g/dL and requiring blood transfusions just during exacerbations, to values below 8.5 g/dLin the most severe cases, being transfusion-dependent and fatal in the worst cases. Most severe cases are transfusion-dependent even after splenectomy, the most agresive palliative treatment...
Pyruvate kinase deficiency (PKD) is the main cause of chronic non-spherocytichemolytic anemia. This disease is a monogenic recessive disorder that occurs due to mutations in PKLR gene. Although this gene codifies the expression of two isoforms of pyruvate kinase, expressed in liver and in red blood cell s, only the erythroid lineage is affected. Pyruvate kinase is the enzyme that catalyzes the last step of the glycolysis, a critical exergonic reaction for the energetic survival of erythrocytes. Due to its low prevalence (about 5:20,000), PKD is considered a rare disease. Severity of the disease is variable, ranging from mild cases, having hemoglobin levels around11 g/dL and requiring blood transfusions just during exacerbations, to values below 8.5 g/dLin the most severe cases, being transfusion-dependent and fatal in the worst cases. Most severe cases are transfusion-dependent even after splenectomy, the most agresive palliative treatment...
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Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular, leída el 31-11-2018