scholarly journals Skin fragility, renal malformation and interstitial lung disease due to compound heterozygous ITGA3 mutations

2021 ◽  
Author(s):  
Wiebke Sondermann ◽  
Rainer Büscher ◽  
Henrike Forster ◽  
Florian Stehling ◽  
Judith Fischer ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Compound Heterozygous ◽  
Renal Malformation ◽  
Skin Fragility

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

2020 ◽  
Author(s):  
Alice S Chau ◽  
Bonnie L Cole ◽  
Jason S Debley ◽  
Kabita Nanda ◽  
Aaron BI Rosen ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Heme Oxygenase ◽  
Macrophage Activation ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Heme Oxygenase 1 ◽  
Compound Heterozygous ◽  
Biliverdin Reductase ◽  
Frame Shift

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.264delCTGG (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 that can mimic systemic-onset juvenile arthritis.

scholarly journals Childhood interstitial lung disease due to compound heterozygous mutations of the ABCA3 gene

2020 ◽  
Author(s):  
Kok Joo Chan ◽  
Meow Keong Thong ◽  
Anna Nathan ◽  
Surendran Thavagnanam ◽  
Yusnita Yakob ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations ◽  
Childhood Interstitial Lung Disease

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

2020 ◽  
Author(s):  
Alice S. Chau ◽  
Bonnie L. Cole ◽  
Jason S. Debley ◽  
Kabita Nanda ◽  
Aaron B.I. Rosen ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Heme Oxygenase ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Heme Oxygenase 1 ◽  
Compound Heterozygous ◽  
Biliverdin Reductase ◽  
Frame Shift ◽  
Whole Exome

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 an exceedingly rare autosomal recessive disorder with hallmark features of direct antibody negative hemolytic anemia with normal bilirubin, hyperinflammation and features indicating hemophagocytosis lymphohistiocytosis. Clinical findings have included asplenia, nephritis, hepatitis, and evidence of vasculitis. Pulmonary features and evaluation of the immune response have been limited. Results Here, we present the fifth reported case in literature of a young boy who remarkably also presented with chronic respiratory failure due to nonspecific interstitial pneumonia in addition to infection-triggered recurrent hyperinflammatory flares notable for 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.264delCTGG (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.

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

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alice S. Chau ◽  
Bonnie L. Cole ◽  
Jason S. Debley ◽  
Kabita Nanda ◽  
Aaron B. I. Rosen ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Heme Oxygenase ◽  
Macrophage Activation ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Heme Oxygenase 1 ◽  
Compound Heterozygous ◽  
Biliverdin Reductase ◽  
Frame Shift

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.

Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations

2013 ◽  
Vol 172 (7) ◽  
pp. 953-957 ◽  
Author(s):  
Hiroshi Kitazawa ◽  
Kunihiko Moriya ◽  
Hidetaka Niizuma ◽  
Kengo Kawano ◽  
Yuka Saito-Nanjo ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Compound Heterozygous

Cellular mechanisms of interstitial lung disease in children caused by mutations of the ABCA3-transporter

Pneumologie ◽  
2010 ◽  
Vol 64 (01) ◽  
Author(s):  
N Weichert ◽  
E Kaltenborn ◽  
A Hector ◽  
M Woischnik ◽  
S Moslavac ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cellular Mechanisms
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