Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. It is caused by mutations of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited antibody deficiency. To our knowledge, this is the first report of XLA from Vietnam. METHODS: We investigated the BTK gene mutations and clinical features of four unrelated Vietnamese children. RESULTS: The mean ages at onset and at diagnosis were 2.5 and 8 years, respectively. All patients had a medical history of otitis media, pneumonia, and septicemia at the time of diagnosis. Other infections reported included sinusitis, bronchiectasis, arthritis, skin infections, meningitis, and recurrent diarrhea. We identified one previously reported mutation (c.441G >A) and three novel mutations: two frameshifts (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T). CONCLUSIONS: The delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results further support the importance of molecular genetic testing in diagnosis of XLA.

Outcomes of laparoscopic choledochotomy using cholangioscopy via percutaneous-choledochal tube for the treatment of hepatolithiasis and choledocholithiasis: A preliminary Vietnamese study.

Backgrounds/Aims: Hepatolithiasis and choledocholithiasis are frequent pathologies and unfortunately, with the current treatment strategies, the recurrence incidence is still high. This study aimed to assess the outcomes of laparoscopic choledochotomy using cholangioscopy via the percutaneous-choledochal tube for the treatment of hepatolithiasis and choledocholithiasis in Vietnamese patients. Methods: A cross-sectional study of patients with hepatolithiasis and/or choledocholithiasis who underwent laparoscopic choledochotomy using intraoperative cholangioscopy via percutaneous-choledochal tube at the Department of Hepatopancreatobiliary Surgery, 108 Military Central Hospital, from June 2017 to March 2020. Results: A total of 84 patients were analyzed. Most patients were females (56.0%) with a median age of 55.56 years. Among them, 41.8% of patients had previous abdominal operations, with 33.4% having choledochotomy. All patients underwent successful laparoscopic common bile duct exploration followed by T-tube drainage without needing to convert to open surgery. Most patients (64.3%) had both intrahepatic and extrahepatic stones. The rate of stones ≥ 10 mm in diameter was 64.3%. Biliary strictures were observed in 19.1% of patients during cholangioscopy. Complete removal of stones was achieved in 54.8% of patients. Intraoperative complications were encountered in two patients, but there was no need to change the strategy. The mean operating time was 121.85 ± 30.47 minutes. The early postoperative complication rate was 9.6%, and all patients were managed conservatively. The residual stones were removed through the T-tube tract by subsequent choledochoscopy in 34/38 patients, so the total success rate was 95.2%. Conclusions: Laparoscopic choledochotomy combined with cholangioscopy through the percutaneous-choledochal tube is a safe and effective strategy for hepatolithiasis and/or choledocholithiasis, even in patients with a previous choledochotomy.

Clinical and immunophenotypic features of atypical complete DiGeorge syndrome.

BACKGROUND: DiGeorge syndrome is a congenital malformation characterized by variable defects of the thymus, heart and parathyroid glands. Athymic patients are classified as exhibiting complete DiGeorge syndrome. Some of these patients may also exhibit oligoclonal T-cell expansion, generalized rash and lymphadenopathy at some point after birth. This rare condition is known as atypical complete DiGeorge syndrome, resembles Omenn syndrome, and has not been fully characterized. METHODS: The clinical and immunophenotypic features of atypical complete DiGeorge syndrome were assessed in two affected Japanese infants. T-cell receptor (TCR) Vß repertoire was analyzed on flow cytometry and complementarity-determining region 3 spectratyping. RESULTS: Both patients had no detectable thymus tissue and profound T-cell lymphopenia soon after birth. Progressive increase of activated T cells, however, as well as eosinophilia, high serum IgE level, generalized rash, and lymphadenopathy were observed during early infancy. A highly restricted TCR Vß repertoire was demonstrated both in CD4(+) and CD8(+) T cells. CONCLUSIONS: The Omenn syndrome-like manifestations might be associated with the oligoclonal proliferation of activated T cells. Analysis of the immunophenotype and TCR Vß repertoire is helpful to establish the early diagnosis of atypical complete DiGeorge syndrome.

Phenotype and genotype features of Vietnamese children with pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). PC is an extremely rare condition. To our knowledge, this is the largest genotype-phenotype study of PC in a Vietnamese population to date. MATERIALS AND METHODS: We investigated keratin gene mutations and clinical features of seven Vietnamese children with PC. RESULTS: The seven Vietnamese patients were from six different families (two patients in the same family) from across Northern, Central, and Southern Vietnam. All children displayed PC symptoms before 1 year of age, but diagnosis was delayed in 4/7 patients. Thick fingernails, thick toenails, oral leukokeratosis, and follicular hyperkeratosis were the most common features recorded by all seven patients. Plantar keratoderma and thick fingernails were the clinical features associated with the most significant effect on daily function. All patients had mutations in KRT6A (PC-K6a) focused on the 1A and 2B domains. We found three distinct types of mutations (K6a R466P, K6a N171K, and K6a N172del). One mutation (N172del) was common to 5/7 (71.4%) of the patients. CONCLUSIONS: Individuals displaying nail dystrophy, oral leukokeratosis, follicular hyperkeratosis, and plantar keratoderma should be referred for genetic testing given the high likelihood of a PC-K6a-related mutation in patients with this constellation of clinical signs.

Clinical Epidemiology Characteristics and Etiology of Febrile Neutropenia in Children: Analysis of 421 Cases.

The congenital immune system includes neutrophils, which perform a variety of functions. Congenital and acquired neutropenia are rare illnesses with an underestimated prevalence in children. The aim of this study is to examine the epidemiology and etiology of febrile neutropenia in children at Haiphong Children's Hospital, Haiphong, Vietnam. Methods: A cross-sectional study was carried out on 421 febrile neutropenia children. Clinical and laboratory characteristics were examined. Results: The median age (IQR) was 25.0 (12.5-59.5) months. The male-to-female ratio was 1.35/1. There were twice as many children living in the suburbs (66.98%) as in urban areas (33.02%). The mean (SD) temperature at admission was 38.50 ± 0.59 °C. Diagnosed causes associated with neutropenia included acute respiratory infections 250 (59.45%), gastrointestinal infections 68 (16.1%), erythema 37 (8.79%), acute leukemia 15 (3.56%), urinary tract infection 5 (1.19%), and encephalitis/meningitis 4 (0.95%). Viral etiology accounted for 61.52% (259): influenza type A-50.19% (130), influenza type B-31.27% (81), dengue virus-14.67% (38), measles virus 1-93% (5), rotavirus-1.54% (4), and EBV-0.4% (1). Twenty-five patients (5.94%) were found to have bacteria in their cultures, with Streptococcus pneumonia being the most common (eight patients; 32%). Conclusions: Febrile neutropenia was common in children under 2 years old. Primary clinical manifestations were acute upper respiratory tract infections, and viruses most commonly caused febrile neutropenia. Further studies with larger sample sizes are needed to determine the cause of febrile neutropenia.

Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia.

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

Severe congenital neutropenia caused by the ELANE gene mutation in a Vietnamese boy with misdiagnosis of tuberculosis and autoimmune neutropenia: a case report.

BACKGROUND: Severe congenital neutropenia (SCN) is an immunodeficiency disease characterized low blood neutrophil counts, early bacterial infections, and risk of leukaemia development. Heterozygous mutations in the ELANE gene coding neutrophil elastase are associated with SCN. Patients with SCN suffer from recurrent bacterial infections and often succumb them. To our knowledge, this is the first report of SCN from Vietnam. CASE PRESENTATION: A 6-year-old boy was admitted due to severe bacterial infection and severe neutropenia. He had recurrent infections from 8 months of age, and was misdiagnosed with tuberculosis and and autoimmune neutropenia in infancy at 21 and 41 months of age, respectively. His medical report has showed severe neutropenia for many times. In direct DNA sequencing analysis, we found an ELANE gene mutation (R81P), which had been confirmed to cause SCN. CONCLUSION: The missed and delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results indicate further evidence for the role of ELANE in SCN.

A case of acute encephalopathy with hemophagocytic lymphohistiocytosis and clonal T-cell expansion.

We report on a 9-year-old boy who presented with acute encephalopathy and hemophagocytic lymphohistiocytosis (HLH). The patient was referred to our hospital because of fever, seizures, and decreased consciousness. He showed moderately elevated levels of proinflammatory cytokines in the cerebrospinal fluid and plasma, and clonal expansion of highly activated CD8⁺ T cells in the peripheral blood. These CD8⁺ T cells were found to be larger cells that stained positive for T-cell receptor Vß13.6, and decreased shortly after steroid therapy. Our findings suggest that his acute encephalopathy was likely a clinical manifestation of HLH, and that immunophenotypic analysis may be helpful for early recognition of HLH in such rare encephalopathy.