Clinical characteristics of aseptic meningitis induced by intravenous immunoglobulin in patients with Kawasaki disease

<p>Abstract</p> <p>Background</p> <p>Aseptic meningitis is a serious adverse reaction to intravenous immunoglobulin (IVIG) therapy. We studied the clinical characteristics of patients with acute Kawasaki disease (KD) who developed IVIG-induced aseptic meningitis.</p> <p>Methods</p> <p>A retrospective analysis of the medical records of patients with KD who developed aseptic meningitis after IVIG treatment was performed.</p> <p>Results</p> <p>During the 10-year period from 2000 through 2009, among a total of 384 patients with Kawasaki disease, 4 (3 females and 1 male; age range, 19-120 months) developed aseptic meningitis after IVIG. All 4 developed aseptic meningitis within 48 hours (range, 25-40 hours) of initiation of IVIG. The analyses of cerebrospinal fluid (CSF) revealed elevated white blood cell counts (22-1,248/μL) in all 4 patients; a predominance of polynuclear cells (65%-89%) was noted in 3. The CSF protein level was elevated in only 1 patient (59 mg/dL), and the glucose levels were normal in all 4 patients. Two patients were treated with intravenous methylprednisolone; the other 2 children were observed carefully without any special therapy. All patients recovered without neurological complications.</p> <p>Conclusions</p> <p>In our patients with Kawasaki disease, aseptic meningitis induced by IVIG occurred within 48 hours after initiation of IVIG, resolved within a few days, and resulted in no neurological complications, even in patients who did not receive medical treatment.</p

Biallelic variants in the ectonucleotidase ENTPD1 cause a complex neurodevelopmental disorder with intellectual disability, distinct white matter abnormalities, and spastic paraplegia.

OBJECTIVE: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia (HSP) is associated with over 80 genes with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (MIM# 615683). METHODS: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterizations were performed. RESULTS: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described: c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs* 18), c.640del; p.(Gly216Glufs* 75), c.185T>G; p.(Leu62*), c.1531T>C; p.(*511Glnext* 100), c.967C>T; p.(Gln323*), c.414-2_414-1del, and c.146 A>G; p.(Tyr49Cys) including four recurrent variants c.1109T>A; p.(Leu370* ), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include: childhood-onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrates ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism. INTERPRETATION: The ENTPD1 locus trait consists of childhood disease-onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1: i) expands previously described features of ENTPD1-related neurological disease, ii) highlights the importance of genotype-driven deep phenotyping, iii) documents the need for global collaborative efforts to characterize rare AR disease traits, and iv) provides insights into the disease trait neurobiology. This article is protected by copyright. All rights reserved