Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis.

Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged < 18 years) who underwent dual genomic sequencing were enrolled in this retrospective multicentre study. We evaluated the mitochondrial disease criteria (MDC) and molecular diagnostic yield of dual genomic sequencing. Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND6 and POLG; MT-ND5 and RARS2; MT-TL1 and NARS2; MT-CO2 and NDUFS1; MT-CYB and SMARCA2; and CHRNA4 and MT-CO3). Based on the MDC, 15.2% of the patients with mitochondria-related variants were classified as "unlikely to have mitochondrial disorder". Moreover, 4.5% of the patients with non-mitochondria-related variants and 1.43% with negative genetic tests, were classified as "probably having mitochondrial disorder". Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.

[Effect on ankylosing spondylitis at early-middle stage and bone marrow edema of sacroiliac joint treated with acupuncture and governor vessel moxibustion].

OBJECTIVE: To observe the efficacy of the combined treatment with acupuncture and governor vessel moxibustion on ankylosing spondylitis (AS) at early-middle stage and investigate the effect on bone marrow edema of sacroiliac joint. METHODS: Seventy patients of AS at early-middle stage were randomized into an observation group (35 cases) and a control group (35 cases, 1 case dropped off ). In the control group, the recombinant human tumor necrosis factor receptor-antibody of type Ⅱ fusion protein for injection was injected subcutaneously, 25 mg each time, once on every Monday and Friday, consecutively for 3 weeks. In the observation group, on the base of the intervention as the control group, acupuncture combined with governor vessel moxibustion were provided. Acupuncture was applied to Dazhui (GV 14), Changqiang (GV 1), Zhibian (BL 54), Baihui (GV 20), etc.; the thermal needling technique was adopted at Dazhui (GV 4) and Changqiang (GV 1) for promoting the circulation of the governor vessel, and the ginger-isolated moxibustion on the governor vessel was combined. Such intervention measure was provided once daily. One treatment session contained 7 treatments and 3 sessions were required. Before and after treatment, the scores of Spondyloarthritis Research Consortium of Canada (SPARCC), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis patient global score (BAS-G) were observed in the two groups separately. The efficacy and adverse effects were assessed in the two groups after treatment. RESULTS: The scores of SPARCC, BASDAI, BASFI and BAS-G were all reduced after treatment compared with those before treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 82.4% (28/34) in the control group (P<0.05). There were 4 cases of gastrointestinal reactions and 1 case of skin rashes in the control group; and 3 cases of local skin redness and pruritus after governor vessel moxibustion, no any drug adverse effect was found in the observation group. CONCLUSION: Based on the western medicine treatment, the combined therapy of acupuncture and governor vessel moxibustion may relieve bone marrow edema of sacroiliac joint in patients with AS at early-middle stage, control the progression of disease and improve the daily life activity. This therapy is relatively safe and effective.

Novel Mutations in the GTPBP3 Gene for Mitochondrial Disease and Characteristics of Related Phenotypic Spectrum: The First Three Cases From China.

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3. Patient 2 was a compound heterozygote with novel mutations c.544G > T (p. G182X) and c.785A > C (p.Q262P), while patient 3 was a compound heterozygote with a previously reported mutation c.424G > A (p.E142K) and novel mutation c.785A > C (p.Q262P). In conclusion, we first describe three Chinese individuals with COXPD23, and discuss the genotype-phenotype correlations of GTPBP3 mutations. Our findings provide novel information in the diagnosis and genetic counseling of patients with mitochondrial disease.

Carnitine-acylcarnitine translocase deficiency with c.199-10 T>G and novel c.1A>G mutation: Two case reports and brief literature review.

RATIONALE: Carnitine-acylcarnitine translocate deficiency (CACTD) is a rare and life-threatening, autosomal recessive disorder of fatty acid ß-oxidation characterized by hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy, liver dysfunction, and muscle weakness; culminating in early death. To date, CACTD cases screened from the Chinese mainland population, especially patient with compound heterozygote with c.199-10T>G and a novel c.1A>G mutation in the SLC25A20 gene has never been described. PATIENT CONCERNS: Herein, we report 2 neonatal cases of CACTD identified from the mainland China. These 2 patients were presented with severe metabolic crisis and their clinical conditions deteriorate rapidly and both died of cardiorespiratory collapse in the first week of life. We present the clinical and biochemical features of 2 probands and a brief literature review of previously reported CACTD cases with the c.199-10T>G mutation. DIAGNOSES: The acylcarnitine profiles by tandem-mass-spectrometry and the mutation analysis of SLC25A20 gene confirmed the diagnosis of CACTD in both patients. Mutation analysis demonstrated that patient No. 1 was homozygous for c.199-10T>G mutation, while patient No. 2 was a compound heterozygote for 2 mutations, a maternally-inherited c.199-10T>G and a paternally-inherited, novel c.1A>G mutation. INTERVENTIONS: Both patients were treated with an aggressive treatment regimen include high glucose and arginine infusion, respiratory, and circulatory support. OUTCOMES: The first proband died 3 days after delivery due to sudden cardiac arrest. The second patient's clinical condition, at one time, was improved by high glucose infusion, intravenous arginine, and circulatory support. However, the patient failed to wean from mechanical ventilation. Unfortunately, her parents refused further treatment due to fear of financial burdens. The patient died of congestive heart failure in the 6th day of life. LESSONS: We report the first 2 cases of CACTD identified from the mainland China. Apart from a founder mutation c.199-10T>G, we identified a novel c.1A>G mutation. Patients with CACTD with a genotype of c.199-10T>G mutation usually presents with a severe clinical phenotype. Early recognition and appropriate treatment is crucial in this highly lethal disorder. This case series highlights the importance of screening for metabolic diseases including CACTD in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period.

Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study.

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.

Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

Multiple therapeutic effects of adjunctive baicalin therapy in experimental bacterial meningitis.

This study aimed to examine effects of adjunctive baicalin therapy to ampicillin for experimental bacterial meningitis in rabbits. After Escherichia Coli inoculation, mean leukocyte counts, concentrations of protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and lactate in cerebrospinal fluid (CSF), brain water content and mean arterial and intracranial pressures substantially increased in the meningitis group. Ampicillin alone for 5 h markedly exacerbated the enhanced leukocyte counts and protein concentration, and showed no significant effect on the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone, C(21)H(18)O(11)) completely counteracted ampicillin-induced exacerbation, and further alleviated the enhanced mean leukocyte counts and protein concentration when combined with ampicillin. Adjunctive baicalin also significantly ameliorated the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicillin, as an adjunctive treatment exerted multiple therapeutic effects in experimental bacterial meningitis.