Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares

Pediatric Rheumatology Online Journal

Deborah A. Nickerson¹  Michael J. Bamshad¹  Eric J. Allenspach²  Aaron B. I. Rosen²  Jason S. Debley²  Bonnie L. Cole³  Kabita Nanda⁴  Alice S. Chau⁵  Troy R. Torgerson⁶ 

[1] Brotman Baty Institute for Precision Medicine;Center for Immunity and Immunotherapies, Seattle Children’s Research Institute;Department of Pathology and Laboratory Medicine, University of Washington;Department of Pediatrics, University of Washington;Division of Allergy & Infectious Disease, Department of Medicine, University of Washington;Experimental Immunology, Allen Institute;

关键词: HMOX1;    Heme oxygenase-1;    HO-1;    NSIP;    Systemic juvenile idiopathic arthritis;    Macrophage activation syndrome;   

DOI  :  10.1186/s12969-020-00474-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown