Clinical and Genetic Features of 5 Chinese Patients with X‐linked lymphoproliferative Syndrome

Abstract

In this study, we report the clinical and genetic features of Chinese patients with X-linked lymphoproliferative syndrome (XLP). Male patients with fulminant infectious mononucleosis (FIM), Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) or persistent EBV viremia were enrolled in this study. Direct sequencing was used to detect SH2D1A/XIAP gene mutations. The patients' clinical features were assessed by retrieval of data from medical records. Twenty-one male patients with FIM, EBV-associated HLH or persistent EBV viremia were evaluated. Four patients had SH2D1A mutations, and one patient had an XIAP mutation. All five of these patients had symptoms of HLH and EBV infection. Among the five patients, the youngest one was only 1 month old at onset. One patient exhibited hypogammaglobulinemia. Of four patients evaluated for immunological function, all exhibited reduced CD4/CD8 ratios. Three patients had rapid disease progression and died. One patient received haematopoietic stem cell transplantation and is well. The overall clinical phenotypes of Chinese patients with XLP matched previous reports. For patients with severe EBV-associated HLH, our results indicate the need to examine the possibility of XLP.

Variable clinical phenotypes of X-linked lymphoproliferative syndrome in China: Report of five cases with three novel mutations and review of the literature

“…Although several large cohort of PID patients were reported in China in recent years, cases of XLP were so limited (Table 4). Until now, there are 21 genetic identified cases totally reported (19 cases in fact because we confirmed that P4, P6 and P7 was the same patient reported in different PID centres, Tables 1 and 3) with the biggest sample of 5 cases [11]. As China is the most populated nation in the world, based on the estimated prevalence, there should be about 1000-4000 XLP patients.…”

“…Three novel mutations were found, two in SH2D1A gene (P1 and P2) and one in XIAP gene (P18). The mutations of Patients 3 and 4 were reported in the previous studies [13,11] (Table 3, P1-P4, P18).…”

“…All patients (5/5) in Wang's study [11] had reduced CD4/CD8 ratio. Booth [14] found 12 in 57 XLP patients (21%) had a reversed CD4:CD8 ratio.…”

“…However, little was known about Chinese patients with XLP. Up to date, few cases of XLP were identified in local China [11]. Here we report the characterization of five Chinese XLP patients with three novel mutations and review the literature related to this syndrome.…”

Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

“…The phenotypic expression includes fulminant infectious mononucleosis, hemophagocytic l y m p h o h i s t i o c y t o s i s ( H L H ) , l y m p h o m a a n d dysgammaglobulinemia, often triggered by EBV infection. [1][2][3] In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific inflammatory pattern and demyelination. In this report, we highlight the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings in a child with EBV induced HLH in XLP.…”