ABSTRACT
Objective:To understand the clinical manifestations, diagnosis, treatment, and prognosis of children with hereditary thrombocytopenia (HT).Methods:The clinical data of 5 patients with HT in the Hematology and Oncology Department of Children′s Hospital of Chongqing Medical University from August 2015 to October 2017 were retrospectively analyzed. The clinical and laboratory characteristics, treatment, and prognosis of HT were discussed by reviewing relevant literatures.Results:Five patients included 3 boys and 2 girls.The median age at onset of 4 years and 2 months old and the median age at diagnose was 4 years and 4 months old.All patients presented with the thrombocytopenia, among which 4 cases were macrothrombocytopenia and 1 case was normothrombocytopenia.The main clinical presentations of 5 patients were skin petechiae and ecchymoses.Four cases were initially misdiagnosed as immune thrombocytopenia (ITP) and received the glucocorticoid and immunoglobulin, while the therapeutic effect was not satisfactory.The gene sequencing confirmed MYH9 gene mutation(c.3493C>T), MYH9 gene mutation(c.5878G>A), NBEAL2 gene compound heterozygous mutation(c.295C>T; c.4169C>T), GP1BA gene mutation(c.1761A>C), and ANKRD26 gene mutation(c.5123A>G), in 5 patients respectively. Conclusions:HT should be suspected among those with recurrent isolated thrombocytopenia and no response to the ITP regimen, and the early gene screening is of great significance to the patients′ treatment and prognosis.
ABSTRACT
Objective@#To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) .@*Methods@#A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed.@*Results@#The patient had 4 episodes of pneumonias and one otitis media since the age of 6 months. The serum immunoglobulin levels were IgG 2.73 g/L, IgA<0.07 g/L, and IgM 0.12 g/L. The percentage of peripheral lymphocyte subsets demonstrated increased CD3+T lymphocyte (81.8%), increased CD4+ naïve T cell (39.1%), normal B cell (14.1%), low switched memory B and plasmablast B (respectively 0.1% and 0), and lightly diminished natural killer(NK) cell (4.13%). Within the peripheral CD4+T cells, the percentage of regulatory T cells (1.49% (control 4.08%)), T follicular helper (3.66% (control 11.0%)), and T helper 17 (9.65% (control 15.7%)) were decreased, while the percentage of T helper 2 (60.9% (control 46.5%)) was elevated. T lymphocyte proliferative response and T cell receptor repertoire diversity were normal. NK-cell cytotoxic activity was impaired. The whole-exome sequencing harbored a de novo heterozygous nonsense mutation in exon 22 (c.2557C>T; p. Arg853X) in the C-terminus of NF-κB2. The western blotting confirmed the decreased expression of NF-κB2 (p52) protein. The patient received intravenous immunoglobulin infusion monthly (400-600 mg/kg), followed by improvement of pulmonary infection. After searching the databases, a total of 28 cases (1 Chinese and 27 non-Chinese) were identified. There were 12 cases of nonsense mutation (5 were gain-of-function mutation), and 8 cases of missense and frameshift mutations, respectively. The main clinical manifestation was respiratory infection, followed by autoimmune diseases such as alopecia and trachyonychia. Fifteen cases developed adrenocorticotrophic hormone (ACTH) deficiency.@*Conclusions@#NF-κB2 signaling pathway played an important role in T and B lymphocyte differentiation, and NK-cell cytotoxic activity. NFκB2 mutation should be considered in cases with recurrent infections, hypogammaglobulinemia, and decreased memory B cells and plasma cells, especially when combined with ACTH deficiency.