Browsing by Author "Liang, Wen-Chen"

Now showing 1 - 12 of 12

Combined Noninvasive Ventilation and Mechanical In-Exsufflator in the Treatment of Pediatric Acute Neuromuscular Respiratory Failure
(2014-06-01)
Chen, Tai-Heng
;
Hsu, Jong-Hau
;
Wu, Jiunn-Ren
;
Dai, Zen-Kong
;
Chen, I-Chen
ObjectivesThe present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in-exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD). MethodsA prospective study was conducted in the pediatric intensive care unit. Children with NMD and ARF treated by combined NIV and MIE were included. Treatment success was defined as freedom from tracheal intubation during the hospital stay. Physiologic indices including PaO2, PaCO2, pH, and PaO2/FiO(2) were recorded before and 12, 24hr after the use of NIV/MIE. ResultsCombined NIV/MIE was used in 15 NMD children (mean: 8.1 years, range: 3 months to 18 years) with 16 cases of ARF. There was no mortality in this cohort. Treatment success was achieved in 12 cases (75%), including six cases (38%) demanding Do Not Intubate. ARF was due to pneumonia, with a mean baseline PaCO2 of 73.219.0mmHg. In the success group, hypercarbia and acidosis improved after use of NIV/MIE for 24hr (PaCO2: 71.7 +/- 18.6mmHg vs. 55.8 +/- 11.6mmHg, P<0.01; pH: 7.29 +/- 0.07 vs. 7.38 +/- 0.05, P<0.01). All patients tolerated NIV/MIE well despite transient skin pressure sores in five cases. ConclusionsCombined NIV/MIE is a safe and effective approach to rapidly improve physiologic indices and decrease the need for intubation in NMD children with ARF. NIV/MIE provides a good alternative for those refusing intubation. Pediatr Pulmonol. 2014; 49:589-596. (c) 2013 Wiley Periodicals, Inc.
Combined noninvasive ventilation and mechanical insufflator-exsufflator for acute respiratory failure in patients with neuromuscular disease: effectiveness and outcome predictors
(2019-09-01)
Chen, Tai-Heng
;
Liang, Wen-Chen
;
Chen, I-Chen
;
Liu, Yi-Ching
;
Hsu, Jong-Hau
Background: To determine the effectiveness of combined noninvasive ventilation (NIV) and mechanical insufflator-exsufflator (MI-E) for acute respiratory failure (ARF) in patients with neuromuscular disease (NMD), and outcome predictors. Methods: A prospectively observational study of patients with ARF was conducted in a pediatric intensive care unit (PICU). All received combined NIV/MI-E during PICU stays between 2007 and 2017. Pertinent clinical variables of heart rate (HR), respiratory rate (RR), pH, PaCO2, and PaO2/FiO(2) ratio were collected at baseline and at 2 h, 4-8 h, and 12-24 h after initiating use of NIV/MI-E. Treatment success was defined as avoiding intubation. Results: A total of 62 ARF episodes in 56 patients with NMD (median age, 13 years) were enrolled. The most frequent underlying NMD was spinal muscular atrophy (32/62, 52%). ARF was primarily due to pneumonia (65%). The treatment success rate was 86%. PICU stay and hospitalization were shorter in the success group (9.4 +/- 6.1 vs. 21.9 +/- 13.9 days and 16.3 +/- 7.8 vs. 33.6 +/- 17.9 days, respectively; both p < 0.05). HR, RR, pH, and PaCO2 showed a progressive improvement, particularly after 4 h following successful NIV/MI-E treatment. RR decrease at 4 h, and pH increase and PaCO2 decrease at 4-8 h might predict success of NIV/MI-E treatment. The multivariate analysis identified PaCO2 at 4-8 h of 58.0 mmHg as an outcome predictor of NIV/MI-E treatment. Conclusions: Applying combined NIV/MI-E in the acute care setting is an efficient means of averting intubation in NMD patients with ARF. Clinical features within 8 h of the institution may predict treatment outcome. The reviews of this paper are available via the supplemental material section.
Comprehensive target capture/next-generation sequencing as a second-tier diagnostic approach for congenital muscular dystrophy in Taiwan
(2017-02-09)
Liang, Wen-Chen
;
Tian, Xia
;
Yuo, Chung-Yee
;
Chen, Wan-Zi
;
Kan, Tsu-Min
Purpose Congenital muscular dystrophy (CMD) is a heterogeneous disease entity. The detailed clinical manifestation and causative gene for each subgroup of CMD are quite variable. This study aims to analyze the phenotypes and genotypes of Taiwanese patients with CMD as the epidemiology of CMD varies among populations and has been scantly described in Asia. Methods A total of 48 patients suspected to have CMD were screened and categorized by histochemistry and immunohistochemistry studies. Different genetic analyses, including next-generation sequencing (NGS), were selected, based on the clinical and pathological findings. Results We identified 17 patients with sarcolemma-specific collagen VI deficiency (SSCD), 6 patients with merosin deficiency, two with reduced alpha-dystroglycan staining, and two with striking lymphocyte infiltration in addition to dystrophic change on muscle pathology. Fourteen in 15 patients with SSCD, were shown to have COL6A1, COL6A2 or COL6A3 mutations by NGS analysis; all showed marked distal hyperlaxity and normal intelligence but the overall severity was less than in previously reported patients from other populations. All six patients with merosin deficiency had mutations in LAMA2. They showed relatively uniform phenotype that were compatible with previous studies, except for higher proportion of mental retardation with epilepsy. With reduced alpha-dystroglycan staining, one patient was found to carry mutations in POMT1 while another patient carried mutations in TRAPPC11. LMNA mutations were found in the two patients with inflammatory change on muscle pathology. They were clinically characterized by neck flexion limitation and early joint contracture, but no cardiac problem had developed yet. Conclusion Muscle pathology remains helpful in guiding further molecular analyses by direct sequencing of certain genes or by target capture/NGS as a second-tier diagnostic tool, and is crucial for establishing the genotype-phenotype correlation. We also determined the frequencies of the different types of CMD in our cohort which is important for the development of a specific care system for each disease.
Congenital muscular dystrophy with fatty liver and infantile-onset cataract caused by TRAPPC11 mutations: broadening of the phenotype
(2015-08-28)
Liang, Wen-Chen
;
Zhu, Wenhua
;
Mitsuhashi, Satomi
;
Noguchi, Satoru
;
Sacher, Michael
Background: Transport protein particle (TRAPP) is a multiprotein complex involved in endoplasmic reticulum-to-Golgi trafficking. Zebrafish with a mutation in the TRAPPC11 orthologue showed hepatomegaly with steatosis and defects in visual system development. In humans, TRAPPC11 mutations have been reported in only three families showing limb-girdle muscular dystrophy (LGMD) or myopathy with movement disorders and intellectual disability. Methods: We screened muscular dystrophy genes using next-generation sequencing and performed associated molecular and biochemical analyses in a patient with fatty liver and cataract in addition to infantile-onset muscle weakness. Results: We identified the first Asian patient with TRAPPC11 mutations. Muscle pathology demonstrated typical dystrophic changes and liver biopsy revealed steatosis. The patient carried compound heterozygous mutations of a previously reported missense and a novel splice-site mutation. The splice-site change produced two aberrantly-spliced transcripts that were both predicted to result in translational frameshift and truncated proteins. Full-length TRAPPC11 protein was undetectable on immunoblotting. Conclusion: This report widens the phenotype of TRAPPC11-opathy as the patient showed the following: (1) congenital muscular dystrophy phenotype rather than LGMD; (2) steatosis and infantile-onset cataract, both not observed in previously reported patients; but (3) no ataxia or abnormal movement, clearly indicating that TRAPPC11 plays a physiological role in multiple tissues in human.
Development of a feasible assay for the detection of GAA mutations in patients with Pompe disease
(2014-02-15)
Er, Tze-Kiong
;
Chen, Chih-Chieh
;
Chien, Yin-Hsiu
;
Liang, Wen-Chen
;
Kan, Tzu-Min
Background: Pompe disease is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA) and is due to pathogenic sequence variants in the corresponding GM gene. While the analysis of enzyme activity remains the diagnostic test of choice for individuals with Pompe disease, mutation analysis remains for establishing a definitive diagnosis. Methods: High resolution melting (HRM) analysis was performed to screen GM mutations. Genomic DNA was extracted from peripheral blood samples of the two patients with Pompe disease and 250 normal controls. Exons 2 through 20 of the GM gene were screened by the HEM analysis. The results were subsequently confirmed by direct sequencing. Results: This assay proved to be feasible in detecting seven known (c2T>C, c.1726G>A, c.1845G>A, c.1935C>A, c.1958C>A, c.2238G>C, and c2815_2816del) GM mutations. Each mutation could be readily and accurately identified in the difference plot curves. We estimated the carrier frequency of the most common mutation, c.1935G>A (p.D645E), in the Taiwanese population to be 02%. Conclusions: In clinical practice, we suggest that HEM analysis is assumed as a fast and reliable method for screening GM gene mutations especially the most common mutations which are responsible for Pompe disease among the Taiwanese populations. (C) 2013 Elsevier B.V. All rights reserved.
IDENTIFICATION A NOVEL MISSENSE MUTATION P.F128S IN A TAIWANESE PATIENT WITH RIBOFLAVIN-RESPONSIVE MULTIPLE ACYL-COA DEHYDROGENASE DEFIENCY
(2011-05-01)
Er, Tze-Kiong
;
Liang, Wen-Chen
;
Chen, Chih-Chieh
;
Liu, Ta-Chi
;
Chang, Jan-Gowth
Limb-girdle muscular dystrophy type 21 is not rare in Taiwan
(2013-08-01)
Liang, Wen-Chen
;
Hayashi, Yukiko K.
;
Ogawa, Megumu
;
Wang, Chien-Hua
;
Huang, Wan-Ting
Alpha-dystroglycanopathy is caused by the glycosylation defects of a-dystroglycan (alpha-DG). The clinical spectrum ranges from severe congenital muscular dystrophy (CMD) to later-onset limb girdle muscular dystrophy (LGMD). Among all alpha-dystroglycanopathies, LGMD type 21 caused by FKRP mutations is most commonly seen in Europe but appears to be rare in Asia. We screened uncategorized 40 LGMD and 10 CMD patients by immunohistochemistry for alpha-DG and found 7 with reduced a-DG immunostaining Immunoblotting with laminin overlay assay confirmed the impaired glycosylation of a-DG. Among them, five LGMD patients harbored FKRP mutations leading to the diagnosis of LGMD2I. One common mutation, c.948delC, was identified and cardiomyopathy was found to be very common in our cohort. Muscle images showed severe involvement of gluteal muscles and posterior compartment at both thigh and calf levels, which is helpful for the differential diagnosis. Due to the higher frequency of LGMD2I with cardiomyopathy in our series, the early introduction of mutation analysis of FKRP in undiagnosed Taiwanese LGMD patients is highly recommended. (C) 2013 Published by Elsevier B.V.
NEURITE GROWTH COULD BE IMPAIRED BY ETFDH MUTATION BUT RESTORED BY MITOCHONDRIAL COFACTORS
(2017-09-01)
Liang, Wen-Chen
;
Lin, Yen-Fong
;
Liu, Ting-Yuan
;
Chang, Shin-Cheng
;
Chen, Bai-Hsiun
Introduction: c. 250G>A (p.Ala84Thr) in ETFDH is the most common mutation that causes later-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) in the southern Chinese population. No functional study has targeted this mutation. Methods: Using cells expressing ETFDH-wild-type (WT) or ETFDH-mutant (p.Ala84Thr), reactive oxygen species (ROS) production and neurite length were analyzed, followed by pathomechanism exploration and drug screening. Results: Increased ROS production and marked neurite shortening were observed in the cells expressing the ETFDH-mutant, compared with WT. Further studies demonstrated that suberic acid, an accumulated intermediate metabolite in MADD, could significantly impair neurite outgrowth of NSC34 cells, but neurite shortening could be restored by supplementation with carnitine, riboflavin, or Coenzyme Q10. Conclusions: Neurite shortening caused by the c. 250G>A mutation in ETFDH suggests that neural defects could be underdiagnosed in human patients with MADD. This impairment might be treatable with mitochondrial cofactor supplementation.
Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies
(2017-02-01)
Liang, Wen-Chen
;
Uruha, Akinori
;
Suzuki, Shigeaki
;
Murakami, Nobuyuki
;
Takeshita, Eri
Objective. Antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have recently been associated with immune-mediated necrotizing myopathy, especially in patients with statin exposure. As the data are very limited concerning phenotypes and treatment in paediatric patients, we aimed to identify the paediatric patients positive for anti-HMGCR antibodies and clarify their features and therapeutic strategies. Methods. We screened 62 paediatric patients who were clinically and/or pathologically suspected to have inflammatory myopathy for anti-HMGCR antibodies. We further re-assessed the clinical and histological findings and the treatment of the patients positive for anti-HMGCR antibodies. Results. We identified nine paediatric patients with anti-HMGCR antibodies (15%). This was more frequent than anti-signal recognition particle antibodies (four patients, 6%) in our cohort. The onset age ranged from infancy to 13 years. Five patients were initially diagnosed with muscular dystrophy, including congenital muscular dystrophy. Most patients responded to high-dose corticosteroid therapy first but often needed adjuvant immunosuppressants to become stably controlled. Conclusion. Paediatric necrotizing myopathy associated with anti-HMGCR antibodies may not be very rare. Phenotypes are similar to those of adult patients, but a chronic slowly progressive course may be more frequent. Some patients share the clinicopathological features of muscular dystrophy indicating that recognizing inflammatory aetiology would be challenging without autoantibody information. On the other hand, most patients responded to treatment, especially those who were diagnosed early. Our results suggest the importance of early autoantibody testing in paediatric patients who have manifestations apparently compatible with muscular dystrophy in addition to those who have typical features of inflammatory myopathy.
Probable high prevalence of limb-girdle muscular dystrophy type 2D in Taiwan
(2016-03-15)
Liang, Wen-Chen
;
Chou, Po-Ching
;
Hung, Chia-Cheng
;
Su, Yi-Ning
;
Kan, Tsu-Min
Limb-girdle muscular dystrophy type 2D (LGMD2D), an autosomal-recessive inherited LGMD, is caused by the mutations in SGCA. SGCA encodes alpha-sarcoglycan (SG) that forms a heterotetramer with other SGs in the sarcolemma, and comprises part of the dystrophin-glycoprotein complex. The frequency of LGMD2D is variable among different ethnic backgrounds, and so far only a few patients have been reported in Asia. We identified five patients with a novel homozygous mutation of c.101G>T (p.Arg34Leu) in SGCA from a big aboriginal family ethnically consisting of two tribes in Taiwan. Patient 3 is the maternal uncle of patients 1 and 2. All their parents, heterozygous for c.101G>T, denied consanguineous marriages although they were from the same tribe. The heterozygous parents of patients 4 and 5 were from two different tribes, originally residing in different geographic regions in Taiwan. Haplotype analysis showed that all five patients shared the same mutation-associated haplotype, indicating the probability of a founder effect and consanguinity. The results suggest that the carrier rate of c.101G>T in SGCA may be high in Taiwan, especially in the aboriginal population regardless of the tribes. It is important to investigate the prevalence of LGMD2D in Taiwan for early diagnosis and treatment (C) 2016 Elsevier B.V. All rights reserved.
Reliability and Validity of Outcome Measures of In-Hospital and At-Home Visits in a Randomized, Double-Blind, Placebo-Controlled Trial for Spinal Muscular Atrophy
(2014-12-01)
Chen, Tai-Heng
;
Yang, Yi-Hsin
;
Mai, Hui-Hsia
;
Liang, Wen-Chen
;
Wu, Yi-Ching
We used at-home assessments in a clinical trial to relieve the visit burden for participants. A total of 57 patients with type II or III spinal muscular atrophy were enrolled and 10 of them (7 type II and 3 type III) received at-home assessments. The primary end points were Gross Motor Function Measure, Manual Muscle Test, and serum biomarker. The secondary endpoints were Modified Hammersmith Functional Motor Scale and forced vital capacity. The correlation coefficients and analysis of covariance showed good reliability and validity of all outcome measures. Except for Gross Motor Function Measure and Modified Hammersmith Functional Motor Scale, there were no significant differences in measures between in-hospital and at-home groups (intersubject) or among 3 patients who received both at-home and in-hospital visits (intrasubject). We concluded that at-home assessments could provide sufficient reliability in a controlled trial. This modification could help design a successful clinical trial for spinal muscular atrophy.
The natural history of the patients with Duchenne muscular dystrophy in Taiwan: A medical center experience
(2018-04-01)
Liang, Wen-Chen
;
Wang, Chen-Hua
;
Chou, Po-Ching
;
Chen, Wan-Zi
;
Jong, Yuh-Jyh
Background: Duchenne muscular dystrophy (DMD) is the most common hereditary muscular dystrophy and caused by DMD gene mutation. In addition to progressive proximal muscle weakness, respiratory, orthopedic, and gastrointestinal complications are often observed in DMD. The natural history of patients with DMD in Taiwan has not been reported thus far. Methods: Medical records of 39 patients who received a diagnosis of DMD between 1999 and 2016 at Kaohsiung Medical University Hospital were reviewed. The diagnosis of DMD was confirmed through muscle biopsy or DMD genetic analysis. Results: The mean onset age and mean follow-up period were 2.75 years and 6.76 years, respectively. Seventeen patients (43.5%) had a family history of DMD. The mean full intelligence quotient of the patients was 71.08, and the mean age of walking ability loss was 9.7 years (25 patients). The mean onset age of respiratory insufficiency was 10.64 years with a decline rate of 5.18% per year (25 patients). The mean onset age of cardiomyopathy was 14.69 years (seven patients). The mean onset age of scoliosis was 13.29 years with a progression rate of 11.48 degrees per year (14 patients). Eleven (28.2%) and eight (20.5%) patients had deletions and duplications of DMD, respectively. Fourteen patients (35.9%) had point mutations or small deletions or insertions. Five patients received only multiplex ligation-dependent probe amplification (MLPA) analysis and exhibited neither deletion nor duplication. No mutation was identified in one patient through both MLPA and exon sequencing. Conclusion: The clinical phenotypes and disease course in our cohort were consistent with that reported in previous studies. However, the proportion of point mutations or small deletions or insertions in our study was considerably higher than that in reports from other populations. Cardiac ejection fraction was found not a reliable biomarker for identifying cardiac problems, discovering a better parameter is necessary. Copyright (C) 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.