Case report: Novel compound-heterozygous mutations in the TCN2 gene identified in a chinese girl with transcobalamin deficiency.

Transcobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C>G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.

Percutaneous autologous bone marrow transplantation for the treatment of delayed union of limb bone in children.

BACKGROUND AND PURPOSE: Percutaneous autologous bone marrow transplantation (PABMT) is a minimally invasive therapeutic strategy for the treatment of delayed bone union in adults, which has been confirmed by many studies. However, there is no report on PABMT application in pediatric orthopedic surgery. The aim of this article was to analyze the therapeutic effect of PABMT in children with delayed union of limb bone and its influence in relation to delayed bone union therapy, transplantation period, patients' sex, fracture location, and fracture fixation. METHODS: In this study, 53 patients (aged 3-16 years, with an average age of 6.7 years) with delayed union of long bone (20 femurs, 12 tibiae, 10 humeri, 5 radiuses, 5 ulnas, and 1 fibula) were treated using PABMT. Clinical examination and X-ray were integrated to evaluate the therapeutic effect. RESULTS: All 53 patients were followed up for 2-6 years (average time, 3.5 years). Of the 53 patients, 47 (88.7%) were healed, whereas the other 6 (11.3%) were not, and were subsequently treated by autologous bone grafting. In 30 patients who received their first PABMT treatment 6-8 months after fixation, the clinical cure rate, operation times, and healing time were 83.3%, 5.8±0.5 months, and 2.5±0.6, respectively. In the other 23 patients, whose first PABMT treatments were started within 4 to 6 months after fixation, the clinical cure rate, operation times, and healing time were 95.7% (P=0.167), 3.2±0.3 months (P=0.001), and 1.3±0.6 (P=0.001), respectively. The patients' sex, fracture location, and fracture fixation did not have statistical influence on the clinical efficacy. CONCLUSION: PABMT is a minimally invasive and effective strategy for the treatment of delayed union of limb bone in children. The early surgical treatment facilitates the fracture healing, reduces the number of transplantation, and shortens the course of treatment.

Physiological responses to Tai Chi in stable patients with COPD.

We compared the physiological work, judged by oxygen uptake, esophageal pressure swing and diaphragm electromyography, elicited by Tai Chi compared with that elicited by constant rate treadmill walking at 60% of maximal load in eleven patients with COPD (Mean FEV1 61% predicted, FEV1/FVC 47%). Dynamic hyperinflation was assessed by inspiratory capacity and twitch quadriceps tension (TwQ) elicited by supramaximal magnetic stimulation of the femoral nerve was also measured before and after both exercises. The EMGdi and esophageal pressure at the end of exercise were similar for both treadmill exercise and Tai Chi (0.109±0.047 mV vs 0.118±0.061 mV for EMGdi and 22.3±7.1 cmH2O vs 21.9±8.1 cmH2O for esophageal pressure). Moreover the mean values of oxygen uptake during Tai Chi and treadmill exercise did not differ significantly: 11.3 ml/kg/min (51.1% of maximal oxygen uptake derived from incremental exercise) and 13.4 ml/kg/min (52.5%) respectively, p>0.05. Respiratory rate during Tai Chi was significantly lower than that during treadmill exercise. Both Tai Chi and treadmill exercise elicited a fall in IC at end exercise, indicating dynamic hyperinflation, but this was statistically significant only after treadmill exercise. TwQ decreased significantly after Tai Chi but not after treadmill. We conclude that Tai Chi constitutes a physiologically similar stimulus to treadmill exercise and may therefore be an acceptable modality for pulmonary rehabilitation which may be culturally more acceptable in some parts of the world.

Respiratory motor output during an inspiratory capacity maneuver is preserved despite submaximal exercise.

It is unknown whether respiratory motor output is constrained during exhaustive exercise in healthy adults. We hypothesised that neural inhibition did occur; to test this hypothesis we measured diaphragm EMG from a maximal inspiratory capacity maneuver (EMG(di)-IC) at rest and during exercise. EMG(di)-IC was measured before and after the amplitude of the diaphragm EMG entered a plateau phase in eleven healthy adults undertaking exercise at 60% and 80% of maximal workload achieved from incremental exercise. The mean EMG(di)-IC at rest was 65 ± 16% of the maximum that could be obtained from a battery of inspiratory tasks. Before and after the plateau phase of diaphragm EMG, EMG(di)-IC was 68 ± 13% and 72 ± 12% (p > 0.05) during 60% of the maximum workload, and was 70 ± 13% and 78 ± 13% (p > 0.05) during 80% of the maximum workload achieved on an incremental test. A further sub-study in which 5 participants exercised at 90% of the maximum workload also showed that EMG(di)-IC was not diminished during exercise. Our data show that exercise condition does not reduce the magnitude of EMG(di)-IC. This argues against neural inhibition as feature of submaximal exercise in healthy adults.

Effect of expiratory load on neural inspiratory drive.

BACKGROUND: Neural respiratory drive is usually measured during inspiration, even in patients with chronic obstructive pulmonary disease (COPD) in whom the primary physiological deficit is expiratory flow limitation. The purpose of the study was to test the hypothesis that inspiratory muscle neural respiratory drive could be used to assess expiratory load. METHODS: Ten healthy young men, (26 ± 4) years old, were asked to expire through a tube immersed in water where an expiratory load was required. The load was judged by the depth of the tube in water and the different loads (0 cmH2O, 10 cmH2O, 20 cmH2O and 30 cmH2O) were randomly introduced. Each expiratory load lasted for 3 - 5 minutes and inspiration was unimpeded throughout. Diaphragm electromyogram (EMG) and transdiaphragmatic pressure were recorded by a catheter with 10 metal coils and two balloons. Incremental cycle exercise with and without an expiratory load at 30 cmH2O was also performed. RESULTS: Neural drive during expiratory loaded breathing was larger than during unloaded breathing but neural drive did not increase proportionally with increasing expiratory load; neural drive during expiratory loading at 0, 10, 20 and 30 cmH2O was (10.1 ± 3.1) µV, (16.7 ± 7.3) µV, (18.4 ± 10.7) µV and (22.9 ± 13.2) µV, respectively. Neural drive as a percentage of maximum at the end of exercise with or without load was similar ((57.4 ± 11.0)% max vs. (62.7 ± 16.4)% max, P > 0.05). CONCLUSION: Neural respiratory drive measured at inspiration does not accurately quantify expiratory load either at rest or during exercise.