Early stroke as a primary manifestation of inborn error of immunity

Le résumé fourni par la source

Case presentation: A 6-year-old female patient presented with a history of multiple ischemic and hemorrhagic strokes with one year old, resulting in cerebellar ataxia, nystagmus, and right hemiparesis, associated with recurrent fever and livedo racemosa. She has no siblings, and her parents are not consanguineous. Magnetic Resonance Imaging showed an intraparenchymal hematoma in the left temporal lobe in the acute stage, signs of perilesional ischemia, and hemoventricle signs. Laboratory evaluation shows red blood cells=4.91 x 106/mL, hemoglobin=12.4g/dL, white blood cells=6.1 x 103/mL, neutrophils=4.3 x 103/mL, lymphocytes=1.2 x 103/mL, and platelets=217 x 103/mL. IgE<25IU/mL, IgG=467mg/dL, IgM=13.8mg/dL, and IgA=21.3mg/dL. Lymphocyte subtypes show CD3+=853 cells/microliter (81.2%), CD4/CD8=1.41, CD19+=113 cells/microliter (10%), and CD16/56=81 cells/microliter (8.8%). Due to the clinical history, genetic sequencing of the CECR1 gene was performed, showing a homozygous substitution at position -2 of the splice acceptor site in intron 6, c.847-2G>A. This is a highly conserved region with no alteration in phylogenetic studies and is predicted to be pathogenic. To confirm the functional alteration, the activity of Adenosine Deaminase-2 (ADA-2) was tested in dried blood spot, showing 0.0 mU/g of protein, confirming the loss of gene function and the pathogenicity of the mutation. Discussion: ADA-2 has partial structural homology with ADA-1. Both proteins convert adenosine to inosine and 2‘-deoxyadenosine to 2‘-deoxyinosine. ADA-2 deficiency is an immune dysregulation disease caused by an autosomal recessive mutation in the CECR1 gene, leading to mild immunodeficiency, more evident in B cells, accompanied by recurrent fevers and a spectrum of pathological vascular characteristics. Final comments: The authors presented a child with an inborn error of immunity with the primary manifestation of cerebrovascular disease due to a mutation in the CECR1 gene, causing loss of gene function and confirmed by the extremely reduced activity of ADA-2.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.