Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares
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CASE REPORT
Open Access
Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares Alice S. Chau1,2, Bonnie L. Cole3,4, Jason S. Debley2,5, Kabita Nanda5, Aaron B. I. Rosen2, Michael J. Bamshad4,5,6, Deborah A. Nickerson4,6, Troy R. Torgerson7 and Eric J. Allenspach2,4,5*
Abstract Background: Heme oxygenase-1 (HMOX1) catalyzes the metabolism of heme into carbon monoxide, ferrous iron, and biliverdin. Through biliverdin reductase, biliverdin becomes bilirubin. HMOX1-deficiency is a rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features similar to macrophage activation syndrome. Clinical findings have included asplenia, nephritis, hepatitis, and vasculitis. Pulmonary features and evaluation of the immune response have been limited. Case presentation: We present a young boy who presented with chronic respiratory failure due to nonspecific interstitial pneumonia following a chronic history of infection-triggered recurrent hyperinflammatory flares. Episodes included hemolysis without hyperbilirubinemia, immunodeficiency, hepatomegaly with mild transaminitis, asplenia, leukocytosis, thrombocytosis, joint pain and features of macrophage activation with negative autoimmune serologies. Lung biopsy revealed cholesterol granulomas. He was found post-mortem by whole exome sequencing to have a compound heterozygous paternal frame shift a paternal frame shift HMOX1 c.264_269delCTGG (p.L89Sfs*24) and maternal splice donor HMOX1 (c.636 + 2 T > A) consistent with HMOX1 deficiency. Western blot analysis confirmed lack of HMOX1 protein upon oxidant stimulation of the patient cells. Conclusions: Here, we describe a phenotype expansion for HMOX1-deficiency to include not only asplenia and hepatomegaly, but also interstitial lung disease with cholesterol granulomas and inflammatory flares with hemophagocytosis present in the bone marrow. Keywords: HMOX1, Heme oxygenase-1, HO-1, NSIP, Systemic juvenile idiopathic arthritis, Macrophage activation syndrome, Asplenia, Hemophagocytosis lymphohistiocytosis, Vasculitis
* Correspondence: [email protected] 2 Center for Immunity and Immunotherapies, Seattle Children’s Research Institute, Jack MacDonald Building – 6th floor, 1900 9th Avenue, Seattle, Washington 98101, USA 4 Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If
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