Fatal COVID-19 in an infant prompted an early diagnosis of ZNFX1 deficiency in a sibling
Clinical Immunology
; Conference: 2023 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference. St. Louis United States. 250(Supplement) (no pagination), 2023.
Article
Dans Anglais
| EMBASE | ID: covidwho-20232246
ABSTRACT
Background:
NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. ZNFX1 deficiency in humans is very rare;to date, only fifteen cases have been reported by Vavassori S et al. (10.1016/j.jaci.2021.03.045). The disease presented in all cases as severe viral infections complicated by multisystem inflammation evolved to multiorgan failure with a high mortality rate. Pediatric Allergy and Immunology Section at Queen Rania Children's Hospital in Jordan had confirmed the diagnosis of ZNFX1 deficiency in an infant at his first presentation with severe viral illness based on the positive family history of one sibling death caused by complicated COVID-19 infection. Case presentation A 12-month-old boy was born to consanguineous parents, full-term, with no NICU admission. He was doing well till the age of four months when he was admitted to the hospital with fever, hypoactivity, and maculopapular skin rash. On admission, he was ill, hypoactive, and febrile, and a physical exam showed hepatosplenomegaly and maculopapular skin rash. His lab showed thrombocytopenia, elevated transaminases, hyperferritinemia, and high CRP;he was treated with broad-spectrum antibiotics, but he continued to deteriorate, and his infectious workup was unrevealing, including COVID-19 PCR. His older sibling died at eight months in 2020 when she got a COVID-19 infection, deceased after rapid deterioration evolved to multiorgan failure. Unfortunately, she had no stored DNA, as she was treated at a peripheral hospital. Based on this presentation and the fatal COVID-19 infection, pediatric immunology service got consulted;we did an immunological workup, which showed normal lymphocyte subsets, Immunoglobulins, and bacterial antibodies. Whole exome sequencing showed a homozygous frameshift mutation in the ZNFX1 gene, protein change defect had detected;p.Tyr555MetfsTer6, and nucleotide change variant c.1663_1665delTACinsAT. Family screening showed heterozygous for the same variant in both parents and a healthy sibling. The patient was diagnosed with the hemophagocytic lymphohistiocytosis-like disease and treated with steroids, intravenous immunoglobulin, and antimicrobials, he showed complete recovery, and we are going to do bone marrow transplantation as his brother is 8/8 HLA matched.Copyright © 2023 Elsevier Inc.
Fatal COVID-19; hlh; znfx1; bone marrow transplantation; brother; case report; child; clinical article; complication; conference abstract; coronavirus disease 2019; deterioration; diagnosis; drug therapy; early diagnosis; family history; female; fever; frameshift mutation; gene mutation; genetic association; hemophagocytic syndrome; hepatosplenomegaly; heterozygosity; homozygosity; human; human cell; hyperferritinemia; hypertransaminasemia; hypoactivity; immunology; infant; inflammation; Jordan; lymphocyte subpopulation; male; mortality rate; multiple organ failure; physical examination; rash; surgery; thrombocytopenia; whole exome sequencing; antibiotic agent; bacterium antibody; endogenous compound; human immunoglobulin; immunoglobulin; nucleotide; steroid
Texte intégral:
Disponible
Collection:
Bases de données des oragnisations internationales
Base de données:
EMBASE
Type d'étude:
Étude diagnostique
/
Étude pronostique
Les sujets:
Variantes
langue:
Anglais
Revue:
Clinical Immunology
Année:
2023
Type de document:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS