Pyruvate kinase deficiency

Zanella, Alberto; Bianchi, Paola; Fermo, Elisa

doi:10.3324/haematol.11469

Cited by 55 publications

(54 citation statements)

References 28 publications

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“…5 Hydrops fetalis and death in the neonatal period have been reported in rare cases of PKD. 5 PK is an essential enzyme for the erythrocyte energetic metabolism, because maturation of the RBC is totally dependent on the adenosine triphosphate (ATP) generated by glycolysis, which maintains its integrity and function. [3][4][5][6] ATP deficiency induces irreversible membrane injury, leading to premature erythrocyte destruction in the spleen and liver.…”

Section: Discussionmentioning

confidence: 99%

“…5 PK is an essential enzyme for the erythrocyte energetic metabolism, because maturation of the RBC is totally dependent on the adenosine triphosphate (ATP) generated by glycolysis, which maintains its integrity and function. [3][4][5][6] ATP deficiency induces irreversible membrane injury, leading to premature erythrocyte destruction in the spleen and liver. 7 It also reduces the erythrocyte capacity to protect itself against destruction from free radicals and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

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Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency

Olivier¹,

Więckowska

Piedboeuf³

et al. 2015

Pediatrics

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Unexpected severe cholestasis is part of the presentation in some neonates with hemolytic anemia but is usually self-resolving. Here we report the case of a neonate with pyruvate kinase deficiency (PKD) who presented severe hemolytic anemia at birth, characterized by a rapidly progressive and severe cholestasis with normal γ-glutamyl transpeptidase level associated with hepatic failure. After an extensive investigation to rule out contributing conditions explaining the severity of this patient’s clinical presentation, PKD has remained the sole identified etiology. The patient abruptly died of sepsis at 3 months of age before a planned splenectomy and ongoing evaluation for liver transplantation. To the best of our knowledge, only a few similar cases of severe neonatal presentation of PKD complicated with severe hepatic failure and cholestasis have been reported.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency

Olivier¹,

Więckowska

Piedboeuf³

et al. 2015

Pediatrics

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“…This is the case for the PK-M form of pyruvate kinase. This enzyme catalyzes the second crucial ATP-generative step in glycolysis and exists as four isoenzymes (M1, M2, L, and R) encoded by two separate genes (PK-M and PK-LR), which are expressed in a tissue-specific manner (31,32). The PK-LR gene codes for both PK-L (dominant form in liver) and PK-R (restricted to RBCs) through the use of alternate promoters.…”

Section: Discussionmentioning

confidence: 99%

Extensive Analysis of the Cytoplasmic Proteome of Human Erythrocytes Using the Peptide Ligand Library Technology and Advanced Mass Spectrometry

Roux‐Dalvai

Peredo²,

Simó³

et al. 2008

Molecular & Cellular Proteomics

216

214

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The erythrocyte cytoplasmic proteome is composed of 98% hemoglobin; the remaining 2% is largely unexplored. Here we used a combinatorial library of hexameric peptides as a capturing agent to lower the signal of hemoglobin and amplify the signal of low to very low abundance proteins in the cytoplasm of human red blood cells (RBCs). Two types of hexapeptide library beads have been adopted: amino-terminal hexapeptide beads and beads in which the peptides have been further derivatized by carboxylation. The amplification of the signal of low abundance and suppression of the signal of high abundance species were fully demonstrated by two-dimensional gel maps and nano-LC-MSMS analysis. The effect of this new methodology on quantitative information also was explored. Moreover using this approach on an LTQ-Orbitrap mass spectrometer, we could identify with high confidence as many as 1578 proteins in the cytoplasmic fraction of a highly purified preparation of RBCs, allowing a deep exploration of the classical RBC pathways as well as the identification of unexpected minor proteins. In addition, we were able to detect the presence of eight different hemoglobin chains including embryonic and newly discovered globin chains. Thus, this extensive study provides a huge data set of proteins that are present in the RBC cytoplasm that may help to better understand the biology of this simplified cell and may open the way to further studies on blood pathologies using targeted approaches. Molecular & Cellular Proteomics 7: 2254 -2269, 2008.Mature red blood cells (RBCs) 1 have a life span of approximately 120 days and are optimally adapted for oxygen and carbon dioxide as well as for proton transport. They consist of a plasma membrane that envelopes a viscous concentrated (33%) solution of proteins of which hemoglobin (Hb) constitutes approximately 98% of the global proteome. The absence of nucleus and the loss of cytoplasmic organelles allow the RBC passing through narrow capillaries, with a concomitant drastic shape change, to properly accomplish its most important biological tasks. A number of other vital functions present in RBCs are related to appropriate generation and expenditure of energy. These include the following: (a) initiation and maintenance of glycolysis, (b) cation pumping against electrochemical gradients, (c) synthesis of glutathione and other metabolites, (d) nucleotide catabolism reactions, (e) maintenance of Hb iron in its functional, reduced, ferrous state, (f) protection of enzymatic and structural proteins from oxidative denaturation, and (g) preservation of membrane phospholipid asymmetry.The structure of the RBC membrane (a thin layer that constitutes less than 0.1% of the cell thickness and only 1% of its weight) has been well elucidated in the past 35 years both from the normal and pathological metabolic points of view (1, 2) and, more recently, from a structural point of view via extensive proteomics mapping (3). Regarding the cytoplasmic content of the RBC, most studies have focused on a variety of rare ...

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“…In most cases, the diagnosis is fortuitous, and rarely, the lesions are symptomatic, displaying neurological signs, pleural effusion, cardiac tamponade, and dyspnea [2]. Pyruvate kinase (PK) deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia, transmitted as an autosomal recessive condition, with classical features ranging from mild anemia to a transfusion-dependant disease [3]. We report in this paper a case of dyspnea indicating idiopathic PAH associated with paravertebral hematopoiesis in a patient with PK deficiency.…”

Section: Idiopathic Pulmonary Arterial Hypertension In a Patientmentioning

confidence: 99%

“…Rarely, spinal cord compression, symptomatic pleural effusion, hemothorax, and pulmonary hematopoiesis have been described [2][3][4]. Diagnosis of extramedullary hematopoiesis may be suspected on clinical findings.…”

Section: Idiopathic Pulmonary Arterial Hypertension In a Patientmentioning

confidence: 99%

Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis

et al. 2008

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Pyruvate kinase deficiency

Cited by 55 publications

References 28 publications

Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency

Cholestasis and Hepatic Failure in a Neonate: A Case Report of Severe Pyruvate Kinase Deficiency

Extensive Analysis of the Cytoplasmic Proteome of Human Erythrocytes Using the Peptide Ligand Library Technology and Advanced Mass Spectrometry

Idiopathic pulmonary arterial hypertension in a patient with pyruvate kinase deficiency and paravertebral extramedullary hematopoiesis

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