Clinical characteristics and genetic analysis of a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to compound heterozygous variants of RRM2B gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A).@*METHODS@#Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein.@*RESULTS@#The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants.@*CONCLUSION@#The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.

Early clinical characteristics and drug sensitivity analysis of 18 children died of invasive pneumococcal disease in pediatric intensive care unit / 中华实用儿科临床杂志

Objective:To understand the early clinical characteristics and drug sensitivity results of children died of invasive pneumococcal disease (IPD) in Pediatric Intensive Care Unit (PICU) so as to guide the early clinical identification and treatment.Methods:The early clinical data and drug sensitivity result of children died of IPD in PICU of the Children′s Hospital, Zhengzhou University and Beijing Children′s Hospital, Capital Medical University from May 2015 to May 2019 were retrospectively analyzed.Results:A total of 18 children meeting the criteria were enrolled, including 6 males and 12 females.The median age was 1 year and 9 months (ranged from 2 months and 20 days to 6 years and 7 months), there were 2 cases(11.1%) > 5 years old, and 16 cases(88.9%)≤ 5 years old.There were 17(94.4%) children related to community acquired infection.Among 18 cases, the first symptom was intracranial infection in 10 cases (55.6%), bloodstream infection in 4 cases (22.2%), and pulmonary infection in 3 cases (16.7%). There were 5 cases complicated with virus infection at the same time.Auxiliary examination: all of the 18 cases had anemia and hypoalbuminemia, and 15 cases(93.8%) had HCO 3- reduction.White blood cells(WBC), platelets(PLT) and natural killer (NK) cell decreased in 7 cases (7/18 cases), 12 cases (12/18 cases) and 6 cases (5/16 cases), respectively, but C-reactive protein(CRP), procalcitonin (PCT), lactic acid concentration(LAC), D-dimer (D-Di), international normalized ratio (INR) and B-type natriuretic peptide (BNP) were increased in 12 cases (12/18 cases), 14 cases (14/18 cases), 7 cases (7/17 cases), 14 cases (14/17 cases) and 9 cases (9/9 cases), respectively.Six children(33.3%) did not receive the treatment of sensitive antibiotics before admission.According to the drug sensitivity results: all the 18 strains had multiple-drug resistance(MDR), and the resistance rates of Penicillin, Erythromycin, Tetracycline, Clindamycin and Sulfamethoxazole were 22.2%, 100.0%, 100.0%, 100.0% and 94.4%, respectively, all the strains were sensitive to Vancomycin, Linezolid and Levofloxacin. Conclusions:Most of the children died of IPD in PICU are of community-acquired infection and less than 5 years old.Anemia and hypoalbuminemia are common in the dead children.The decreased in HCO 3- and increased PCT, LAC and D-Di in the early stage might be related to poor prognosis of patients.Most of the children died of IPD are infected with MDR strains.

Analysis of clinical characteristics and prognosis of children with septic shock caused by invasive pneumococcal diseases / 中华实用儿科临床杂志

Objective:To investigate the clinical characteristics and prognosis of children with septic shock caused by invasive pneumococcal diseases (IPDs) in pediatric intensive care unit (PICU).Methods:The clinical data of children diagnosed as septic shock caused by IPDs and hospitalized in the intensive care unit (ICU) of Beijing Children′s Hospital, Capital Medical University and the PICU of Henan Children′s Hospital from January 2013 to August 2019 were retrospectively collected, and the clinical characteristics and prognosis of these patients were analyzed.Results:Twenty-one children were included, with a median age of 1.2 (0.75, 3.90) years old.The pediatric index of mortality 2 (PIM-2) at admitting was (23.3±29.6)%, and 6 cases had underlying diseases.Main sites of infection included blood flow (20 cases) and suppurative meningitis (15 cases). The drug sensitivity test was performed on 18 children, among who 9 cases were sensitive to Penicillin, 10 cases to Cefepime, 11 cases to Cefotaxime and 10 cases to Meropenem.All 18 patients were sensitive to Vancomycin and Linezolid.Seven cases and 13 cases were treated with sensitive antibiotics at the disease onset and before septic shock, respectively.In 21 cases whose lactic acid level was (6.1±4.6) mmol/L, the shock redress time of 10 cases was (10.9±10.1)h, and 13 cases (61.9%) died (14.6±12.2) hours after septic shock, among who 10 died of transforamed magna herniation.The PIM-2 score at admitting into PICU and the rate of intracranial hypertension crisis in the death group were significantly higher than those in the survival group [(37.1±30.3)% vs.(0.9±1.3)%, 69.9% (9/13 cases) vs.25.0% (2/8 cases)](all P<0.05). There was no significant difference in age and the utilization rate of effective antibiotics before septic shock between the two groups (all P<0.05). Four of the surviving 8 children had severe cerebral functional disability. Conclusions:Septic shock caused by IPD is more common in children under 5 years old, and the most common sites are blood flow and intracranial infection.It has high resistance rate against Cephalosporins and Carbopenem.Patients with purulent meningitis are easy to develop intracranial hypertension crisis, which has an extremely high mortality and morbidity, so it needs to be identified and treated early.

The influence of endogenous and exogenous catecholamine on myocardium in septic shock / 中国小儿急救医学

In order to explain the contribution of increase of endogenous catecholamines and exogenous administration of catecholamines to cardiac dysfunction in patients suffering from septic shock,we discussed the effects of application of catecholamines and heart,cardiac toxicity induced by catecholamines,septic shock sympathetic-adrenergic activation state and exogenous administration of catecholamines on the myocardium in sepsis.