Deoxyguanosine kinase deficiency presenting as neonatal hemochromatosis
ABSTRACT Mutations in DGUOK result in mitochondrial DNA (mtDNA) depletion and may present as neonatal liver failure. Neonatal hemochromatosis (NH(1)) is a liver disorder of uncertain and varied etiology characterized by hepatic and non-reticuloendothelial siderosis. To date, deoxyguanosine kinase (dGK(2)) deficiency has not been formally recognized in cases of NH. We report an African American female neonate with clinical and autopsy findings consistent with NH, and mtDNA depletion due to a homozygous mutation in DGUOK. This report highlights hepatocerebral mtDNA depletion in the differential of neonatal tyrosinemia, advocates considering dGK deficiency in cases of NH, and posits mitochondrial oxidative processes in the pathogenesis of NH.
Article: Iron Metabolism in Transplantation[Show abstract] [Hide abstract]
ABSTRACT: Recipient's iron status is an important determinant of clinical outcome in transplantation medicine. This review addresses iron metabolism in solid organ transplantation, where the role of iron as a mediator of ischemia-reperfusion injury, as an immune-modulatory element and as a determinant of organ and graft function is discussed.Although iron chelators reduce ischemia reperfusion injury in cell and animal models, these benefits have not yet been implemented into clinical practice. Iron deficiency and iron overload are associated with reduced immune activation, whose molecular mechanisms are reviewed in detail. Furthermore, iron overload and hyperferritinemia are associated with poor prognosis in end stage organ failure in patients awaiting kidney-, or liver transplantation. This negative prognostic impact of iron overload appears to persist after transplantation, which highlights the need for optimizing iron management before and after solid organ transplantation. In contrast, iron deficiency and anemia are also associated with poor prognosis in patients with end stage heart failure. Intravenous iron supplementation should be managed carefully because parenterally induced iron overload could persist after successful transplantation.In conclusion, current evidence shows that iron overload and iron deficiency are important risk factors before and after solid organ transplantation. Iron status should therefore be actively managed in patients on the waiting list and after transplantation.This article is protected by copyright. All rights reserved.Transplant International 06/2014; 27(11). DOI:10.1111/tri.12374 · 3.16 Impact Factor
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ABSTRACT: Neonatal hemochromatosis is a rare gestational disease resulting in severe fetal liver disease with extrahepatic iron overload sparing the reticuloendothelial system. Recurrrence can be prevented with intravenous immunoglobulin (IVIG) infusions during pregnancy supporting an alloimmune etiology. Our study aimed to assess the effect of antenatal treatment with IVIG on the outcome of pregnancies in women with a past history of documented neonatal hemochromatosis likely due to gestational alloimmune disease (GALD), and to analyse IVIG tolerance.Journal of Pediatric Gastroenterology and Nutrition 07/2014; 59(5). DOI:10.1097/MPG.0000000000000514 · 2.87 Impact Factor
- Hepatology 04/2014; 60(1). DOI:10.1002/hep.27191 · 11.19 Impact Factor