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

Olivier, François; Więckowska, Anna; Piedboeuf, Bruno; Alvarez, Fernando

doi:10.1542/peds.2015-0834

Cited by 17 publications

(19 citation statements)

References 15 publications

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“…Cholestasis and liver dysfunction progressed rapidly, and all 3 died before 5 months of age from posttransplant complications or while awaiting surgery. 4,5 It was therefore suggested by Raphaël et al 5 that liver failure was directly linked to PKD. Although PK-M2 was not measured, we hypothesize that liver failure is related to individual differences in metabolic and proteolytic activity and a compensatory presence or absence of the PK-M2 isoenzyme.…”

Section: Discussionmentioning

confidence: 99%

Successful Liver Transplants for Liver Failure Associated With Pyruvate Kinase Deficiency

et al. 2018

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Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic chronic hemolytic anemia, and patients normally present with mild to severe anemia, unconjugated hyperbilirubinemia, and splenomegaly. Only a few reports of PKD have documented its association with severe, progressive liver failure. In all those cases, the patients died before liver transplant (LT) or immediately after transplant. We report 2 case patients with liver failure associated with PKD who successfully underwent LT and splenectomy: an infant who presented with neonatal cholestasis and a young adult with a severe form of PKD and having been transfusion dependent during childhood. After transplant, both patients have normal liver function test results and have considerably decreased their need for blood transfusion despite ongoing, mild hemolysis. We suggest that PKD can lead to severe liver dysfunction and that LT and splenectomy can be life-saving procedures in such cases.

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Section: Discussionmentioning

confidence: 99%

Successful Liver Transplants for Liver Failure Associated With Pyruvate Kinase Deficiency

et al. 2018

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“…Phototherapy is effective in preventing exchange transfusions in many infants. Rarely, newborns can present with evolving hepatic disease and evidence of a direct hyperbilirubinaemia (Raphael et al , ; Olivier et al , ; Chartier et al , ). One hypothesis of the pathophysiology for this uncommon complication is that certain patients are susceptible to PK‐liver (PK‐L) enzyme deficiency due to both severe deficiencies in PK‐L and the PK‐M2 isoenzyme.…”

Section: Supportive Treatmentsmentioning

confidence: 99%

How we manage patients with pyruvate kinase deficiency

2019

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Summary Novel therapies in development have brought a new focus on pyruvate kinase deficiency (PKD), the most common congenital haemolytic anaemia due to a glycolytic enzyme deficiency. With an improved recognition of its clinical presentation and understanding of the diagnostic pathway, more patients are likely to be identified with this anaemia. Complications, including gallstones and non‐transfusion‐related iron overload, require monitoring for early diagnosis and management. Current management remains supportive with red cell transfusions, chelation and splenectomy. Decisions to transfuse and/or splenectomise must be individualised. Haematopoietic stem cell transplant has been pursued in a small number of patients with mixed outcomes. Novel treatment approaches, which range from a small molecule pyruvate kinase activator to gene therapy, may transform the way in which PKD is managed in the future. In this review, we discuss the pathophysiology of PKD and present our approaches to diagnosis, monitoring and management of patients with this anaemia.

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“…There have been four reported cases of newborns with PK deficiency that developed conjugated hyperbilirubinemia and subsequent liver failure. The specific cause of liver failure remains unclear, with several hypotheses, including the absence of compensatory PK‐M2 isoenzyme activity, intrahepatic bile duct obstruction due to hemolysis, or damage to intrahepatic canaliculi due to extramedullary hepatic hematopoiesis 27–29 . Despite these various potential complications, some newborns with PK deficiency have only mild anemia and an absence of jaundice 27 .…”

Section: Diagnosis and Manifestations Of Pk Deficiencymentioning

confidence: 99%

Diagnosis, monitoring, and management of pyruvate kinase deficiency in children

Johnson

Grace

Despotovic

2022

Pediatric Blood & Cancer

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Pyruvate kinase (PK) deficiency is a rare, congenital red blood cell disorder caused by a single gene defect. The spectrum of genotypes, variants, and phenotypes are broad, commonly requiring a multimodal approach including enzyme and genetic testing for accurate and reliable diagnosis. Similarly, management of primary and secondary sequelae of PK deficiency varies, mainly including supportive care with transfusions and surgical interventions to improve symptoms and quality of life. Given the risk of acute and long-term complications of PK deficiency and its treatment, regular monitoring and management of iron burden and organ dysfunction is critical. Therefore, all children and adolescents with PK deficiency should receive regular hematology care with visits at least every 6 months regardless of transfusion status. We continue to learn more about the spectrum of symptoms and complications of PK deficiency and best practice for monitoring and management through registry efforts (NCT03481738).The treatment of PK deficiency has made strides over the last few years with newer disease-modifying therapies being developed and studied, with the potential to change the course of disease in childhood and beyond.

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

Cited by 17 publications

References 15 publications

Successful Liver Transplants for Liver Failure Associated With Pyruvate Kinase Deficiency

Successful Liver Transplants for Liver Failure Associated With Pyruvate Kinase Deficiency

How we manage patients with pyruvate kinase deficiency

Diagnosis, monitoring, and management of pyruvate kinase deficiency in children

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