Two Brothers with Atypical UNC13D-Related Hemophagocytic Lymphohistiocytosis Characterized by Massive Lung and Brain Involvement

Frontiers in Immunology

Carol Saunders²  Caterina Cancrini³  Roberta Romano⁴  Claudio Pignata⁴  Emilia Cirillo⁴  Giuliana Giardino⁴  Massimiliano Valeriani⁵  Laura Papetti⁵  Paolo Palma⁶  Maia De Luca⁸ 

[1] Center for Pediatric Genomic Medicine, Children’s Mercy-Kansas City, Kansas City, MO, United States;Department of Pathology, Children’s Mercy-Kansas City, Kansas City, MO, United States;Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy;Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy;Neurology Unit, Bambino Gesù Children’s Hospital, Rome, Italy;Research Unit in Congenital and Perinatal Infection, Unit of Immune and Infectious Diseases, University Department of Pediatrics (DPUO), Bambino Gesù Children’s Hospital, Rome, Italy;School of Medicine, University of Missouri-Kansas City, Kansas City, MO, United States;Unit of Immune and Infectious Diseases, University Department of Pediatrics (DPUO), Bambino Gesù Children’s Hospital, Rome, Italy;

关键词: UNC13D;    FHL3;    atypical FHL;    CNS-HLH;    extracorporeal membrane oxygenation;   

DOI  :  10.3389/fimmu.2017.01892

来源: DOAJ

【 摘 要 】

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition. Variants in different genes have been associated with the familial forms of the syndrome (FHL), usually presenting within the first 2 years of life. Due to increasing awareness of the signs and symptoms of HLH and a better understanding of the genetic basis of the disease, FHL has been increasingly diagnosed in patients presenting beyond infancy. Here, we report on two brothers with atypical, late-onset HLH in which whole exome sequencing revealed a homozygous pathogenic UNC13D variant. In the first brother, the clinical phenotype was dominated by a massive lung involvement. In the second brother a progressive neurological deterioration was observed. In both cases, the clinical manifestations at symptom onset were misleading, making the diagnosis difficult to achieve. This report expands the spectrum of clinical presentations of FLH3. Moreover, it highlights the importance to warn clinicians to keep a high level of suspicion in patients presenting with fever, cytopenia, splenomegaly of unknown origin, and unresponsiveness to conventional treatment even beyond early childhood. Moreover, this report emphasizes that insidious neurologic symptoms may represent the initial or sole presenting sign of FHL, even in the absence of peripheral signs of activation.

【 授权许可】

Unknown