Chromobacterium violaceum: A rare opportunistic pathogen and clue for pediatric chronic granulomatous disease.

Chromobacterium violaceum is a rare bacterium found in water and soil in tropical regions and typically presents with a localized skin infection or lymphadenitis which can progress to fulminant septicemia and even death. We describe a case of a 2-year-old boy with C. violaceum septicemia from a suspected skin source which was confirmed by wound, tissue and blood cultures. The discovery of this rare organism, subsequently led to the evaluation and identification of underlying chronic granulomatous disease.

Haematopoietic stem cell transplantation for inborn errors of immunity: 25-year experience from University of Malaya Medical Centre, Malaysia.

AIM: Inborn errors of immunity (IEI) comprise a heterogeneous group of disorders of the immune system, most of which are curable by haematopoietic stem cell transplantation (HSCT). We present a 25-year audit of HSCT for IEI at a tertiary-level academic hospital in Malaysia. METHODS: Review of medical records of all cases of IEI who underwent HSCT between January 1993 and December 2018 at our centre. Diagnoses, complications, HSCT protocols and outcome data were studied. RESULTS: There were 20 patients (19 boys) with a median age at diagnosis of 11 months (range: 2 months to 12 years). Eleven of 19 (58%) had malnutrition at presentation. Donor sources were variable: 13 (65%) matched sibling donor (MSD), 4 (20%) human leukocyte antigen-haploidentical donor (HD) and 3 (15%) matched unrelated donor (MUD). Conditioning regimens were physician-dependent and adapted to each patient's clinical status. Grades III-IV acute graft-versus-host disease occurred in two of three cases who received MUD grafts, 50% in those who received HD, and 8% in the MSD group. Transplant-related mortality at day +100 was 5%. With a median follow-up of 7.5 years, 18 (90%) patients are alive and free of infections. CONCLUSION: Outcome of HSCT for IEI in our centre is comparable with international reports. HSCT results using HD and MUD grafts are also good despite challenges from acute graft-versus-host disease, providing a feasible alternative for patients without matched donors.

Pyoderma Vegetans: A Case Report in a Child Suspected to Primary Immunodeficiency and Review of the Literature.

Pyoderma vegetans (PV) is a rare inflammatory disorder characterized by vegetating pustules and plaques affecting the skin and mucosal membranes. It is believed that this entity is mostly associated with inflammatory bowel disease (IBD), chronic malnutrition, human immunodeficiency virus (HIV), malignancies, and other immunocompromised states. Pyoderma vegetans occurs more commonly in young and middle-aged adults. There is no sex predilection for this entity. The lesions could heal spontaneously, but usually recur and become chronic. Our patient was an 11-year-old girl suspected to have primary combined immunodeficiency complicated by chronic recurrent vegetating pustular lesions on the face and postauricular area since one year of age. The histological features of the lesions were consistent with pyoderma vegetans. This is the first case of PV beginning from early infancy in the setting of primary immunodeficiency and in an unusual location.

[De novo NFκB2 gene mutation associated common variable immunodeficiency].

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.

[Short stature, optic nerve atrophy and Pelger-Huët anomaly syndrome with antibody immunodeficiency and aplastic anemia: a case report and literature review].

Objective: To investigate the clinical features and genetic characteristics of cases with NBAS gene defects. Method: Characteristics of clinical materials, immunological data and gene mutation of the first case in China with NBAS gene mutation were retrospectively analyzed. The related literature was searched by using search terms'NBAS'. Result: A 2-year-four-month old girl, was admitted due to 'fever and pallor for one day'. There was an intrauterine growth retardation at her fetal stage. Since her birth, she had suffered from recurrent infections and development delay was accompanied by persistent liver dysfunction. Her head circumference and height were 43.5 cm and 60 cm, respectively. She seemed pale. She had progeroid appearance with loose skin, sparse hair, proptosis and low-set ears. The cranial suture did no close and the anterior fontanel was about 6 cm×5 cm. Abdominal palpation showed that the liver was 2 cm below the right costal margin, and the spleen was 1.5 cm below the left rib. Both alanine aminotransferase(100-1 991 IU/L) and aspartate aminotransferase (191-1 367 IU/L) were persistently abnormal. Visual evoked potentials and fundus examination revealed optic nerve atrophy. Bone mineral density assessment showed osteoporosis. The IgG level was 2.0 g/L (3.41-19.6) and absolute count of CD19(+)B cells was 231.27/µl (608.8-2 167.7) . Her hemoglobin level was 53 g/L. Bone marrow smear showed serious hypoplasia in erythroid cell. The gene sequencing results showed NBAS gene c.5741C> T, pR1914H and c.6496-6497insA, p.S2166Ffs* 2 compound heterozygous mutations. A total of 8 literatures were collected including 57 cases with NBAS gene homozygous or compound heterozygous mutation. These 57 cases were characterized by short stature(88%, 50/57) , Pelger-Huët anomaly (75%, 43/57) , skeletal dysplasia (74%, 42/57), optic nerve atrophy (72%, 41/57), abnormality of liver enzymes or acute liver failure (42%,24/57), abnormalities of immune system(19%, 11/57), development delay of mental, language or sports(11%, 6/57). Other clinical manifestations such as progeroid appearance, proptosis and hypotonia were also common. NBAS gene c.5741G>A homozygous mutation accounted for 61% (35/57) cases. Conclusion: Cases with NBAS gene defects often manifests as short stature, optic nerve atrophy, Pelger-Huët anomaly, skeletal dysplasia, recurrent infections, abnormality of liver enzymes, progeroid appearance, proptosis, hypotonia and immunodeficiency. Gene sequencing analysis showed NBAS gene homozygous or compound heterozygous mutations, and homozygous mutation of c.5741G>A was most common.