Diagnosis of Pyruvate Kinase Deficiency

Gallagher, Patrick G.; Glader, Bertil

doi:10.1002/pbc.25922

Cited by 13 publications

(15 citation statements)

References 8 publications

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“…Analyzing RBCs of their parents and siblings, as exemplified in this report, is part of a rational diagnostic approach in children with transfusion‐dependent chronic hemolytic anemia …”

Section: Resultsmentioning

confidence: 99%

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Kager

Bruce

Zeitlhofer³

et al. 2016

Pediatric Blood & Cancer

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We describe the second patient with anionic exchanger 1/band 3 null phenotype (band 3 null ), which was caused by a novel nonsense mutation c.1430C>A (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3 null patient, thereby elucidating the physiological implications of total loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and complete distal renal tubular acidosis, dyserythropoiesis was identified in the band 3 null patient, suggesting a role for band 3 in erythropoiesis. Moreover, we also, for the first time, report that long-term survival is possible in band 3 null patients.

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“…Analyzing RBCs of their parents and siblings, as exemplified in this report, is part of a rational diagnostic approach in children with transfusion‐dependent chronic hemolytic anemia …”

Section: Resultsmentioning

confidence: 99%

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Kager

Bruce

Zeitlhofer³

et al. 2016

Pediatric Blood & Cancer

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“…77 They should be con- In line with this, and in contrast to US Centers, all but one EU Center performs such complementary biochemical methods to confirm the pathogenic nature of detected mutations. 77 They should be con- In line with this, and in contrast to US Centers, all but one EU Center performs such complementary biochemical methods to confirm the pathogenic nature of detected mutations.…”

Section: Advantages and Limitations Of Dna Analysismentioning

confidence: 98%

“…In the most severe cases, some erythroblasts may be observed in peripheral blood smear as a consequence of ineffective erythropoiesis. 42 When available, it is very helpful to study parents and other family members to confirm the presumed heterozygous state of the enzyme deficiency, 77 particularly in transfusiondependent cases. [70][71][72] The reticulocyte count in not-splenectomized patients is usually increased.…”

Section: Clinical Aspectsmentioning

confidence: 99%

“…4 Since the hematological features of PK deficiency are not specific, PK deficiency should also be considered in transfusion-dependent patients without obvious etiology, in neonates with unexplained severe hyperbilirubinemia, when reticulocytosis increases after splenectomy of an undiagnosed hemolytic patient or in patients with positive family history of PKD. 42 When available, it is very helpful to study parents and other family members to confirm the presumed heterozygous state of the enzyme deficiency, 77 particularly in transfusiondependent cases. This approach is almost always adopted in EU Reference Centers, but is not always considered elsewhere.…”

Section: Clinical Aspectsmentioning

confidence: 99%

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Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency

et al. 2018

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Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. By the creation of a global PKD International Working Group in 2016, involving 24 experts from 20 Centers of Expertise we studied the current gaps in the diagnosis of PKD in order to establish diagnostic guidelines. By means of a detailed survey and subsequent discussions, multiple aspects of the diagnosis of PKD were evaluated and discussed by members of Expert Centers from Europe, USA, and Asia directly involved in diagnosis. Broad consensus was reached among the Centers on many clinical and technical aspects of the diagnosis of PKD. The results of this study are here presented as recommendations for the diagnosis of PKD and used to prepare a diagnostic algorithm. This information might be helpful for other Centers to deliver timely and appropriate diagnosis and to increase awareness in PKD.

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“…The clinical PKD phenotypes vary from mild anemia and jaundice to severe transfusion‐dependent hemolytic anemia and extreme hyperbilirubinemia in neonates . PKD is usually diagnosed by a positive family history, physical findings, and conventional laboratory evaluation, such as evidence of extravascular hemolysis, examination of a peripheral blood smear, and measurement of the PK levels . However, individuals who are heterozygous carriers of PKD mutations are clinically asymptomatic.…”

Section: Introductionmentioning

confidence: 99%

A novel PKLR gene mutation identified using advanced molecular techniques

Luo

Yonghong

Jia

et al. 2018

Pediatric Transplantation

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This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The proband received cord blood and bone marrow from the second child of the mother for hematopoietic stem cell transplantation and achieved normal hematopoiesis. The genetic characterization analysis and genotype-phenotype correlation study of PKLR gene suggested that NGS was an effective method to confirm the molecular diagnosis of intractable hemolytic anemia. The identification of the mutation aided in prenatal diagnosis in the second pregnancy and the effective clinical management of the affected family.

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Diagnosis of Pyruvate Kinase Deficiency

Cited by 13 publications

References 8 publications

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency

A novel PKLR gene mutation identified using advanced molecular techniques

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Diagnosis of Pyruvate Kinase Deficiency

Cited by 13 publications

References 8 publications

Band 3 nullVIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Band 3 nullVIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency

A novel PKLR gene mutation identified using advanced molecular techniques

Contact Info

Product

Resources

About

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis