TY - JOUR
T1 - Familial CNS-Isolated hemophagocytic lymphohistiocytosis due to a novel PRF1 mutation triggered by SARS-CoV2
AU - Caldito, Natalia
AU - Lorenzo, Jocelyn
AU - Wang, Cynthia
N1 - Publisher Copyright:
© 2022 Wolters Kluwer Medknow Publications. All rights reserved.
PY - 2022/11
Y1 - 2022/11
N2 - Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition that presents with fever, hepatosplenomegaly, and characteristic laboratory findings. Mutations in the perforin gene PRF1 have been implicated in cases of familial HLH (fHLH) and can cause isolated CNS-HLH in the absence of systemic HLH. Results: A five year-old boy presented with three weeks of headache, blurry vision, and emesis. He was diagnosed with acute disseminated encephalomyelitis (ADEM), thought to be triggered by SARS-CoV-2 given positive nasopharyngeal testing. He completed a five day course of high dose IV methylprednisolone and plasma exchange. In the subsequent months, he was admitted twice due to worsening clinical and radiological activity and after several courses of IV pulse steroids, plasmapheresis, and IV immunoglobulin (IVIG), his condition stabilized with rituximab and monthly IVIG. A few months later, his younger brother presented with a similar syndrome. It was discovered that his parents were second cousins, leading to concern for a genetic disorder. Genetic testing revealed a homozygous mutation for PRF1 in both siblings (variant c.4422G>A). Conclusions: This is the first presentation of CNS-isolated familial HLH triggered by SARS-CoV-2 in the pediatric population. Furthermore, this is the first report of this specific PRF1 mutation, the variant c.4422G>A, as pathogenic. It highlights the relevance of genetic testing in pediatric neuroinflammatory disorders that do not respond adequately to conventional treatments. It is possible that as our knowledge in neurogenetics develops, certain genes will be identified as predisposing factors to syndromes such as ADEM.
AB - Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition that presents with fever, hepatosplenomegaly, and characteristic laboratory findings. Mutations in the perforin gene PRF1 have been implicated in cases of familial HLH (fHLH) and can cause isolated CNS-HLH in the absence of systemic HLH. Results: A five year-old boy presented with three weeks of headache, blurry vision, and emesis. He was diagnosed with acute disseminated encephalomyelitis (ADEM), thought to be triggered by SARS-CoV-2 given positive nasopharyngeal testing. He completed a five day course of high dose IV methylprednisolone and plasma exchange. In the subsequent months, he was admitted twice due to worsening clinical and radiological activity and after several courses of IV pulse steroids, plasmapheresis, and IV immunoglobulin (IVIG), his condition stabilized with rituximab and monthly IVIG. A few months later, his younger brother presented with a similar syndrome. It was discovered that his parents were second cousins, leading to concern for a genetic disorder. Genetic testing revealed a homozygous mutation for PRF1 in both siblings (variant c.4422G>A). Conclusions: This is the first presentation of CNS-isolated familial HLH triggered by SARS-CoV-2 in the pediatric population. Furthermore, this is the first report of this specific PRF1 mutation, the variant c.4422G>A, as pathogenic. It highlights the relevance of genetic testing in pediatric neuroinflammatory disorders that do not respond adequately to conventional treatments. It is possible that as our knowledge in neurogenetics develops, certain genes will be identified as predisposing factors to syndromes such as ADEM.
KW - ADEM
KW - PRF1 mutation
KW - autoimmune
KW - hemophagocytic lymphohistiocytosis
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U2 - 10.4103/aian.aian_719_22
DO - 10.4103/aian.aian_719_22
M3 - Article
C2 - 36911442
AN - SCOPUS:85144924940
SN - 0972-2327
VL - 25
SP - 1170
EP - 1173
JO - Annals of Indian Academy of Neurology
JF - Annals of Indian Academy of Neurology
IS - 6
ER -