Dysferlinopathy in a cohort of Chinese patients:clinical features,mutation spectrum,and imaging findings

To the Editor:Mutations in the dysferlin(DYSF)gene lead to dysferlinopathy,which is referred to as a group of muscular dystrophies with autosomal recessive inheri-tance.Dysferlinopathy includes Miyoshi myopathy(MM),limb-girdle muscular dystrophy(LGMD2B),and other atypical phenotypes,such as the“proximo-distal(PD)”phenotype and distal anterior compartment myopathy.Currently.the genotype-phenotype correlation in the majority of patients remains unclear.

UPLC-QTOF-MS FOR METABOLITES IDENTIFICATION IN CACO-2 CELLS OF BENZYLISOQUINOLINE ALKALOIDS IN NELUMBINIS PLUMULA

The aim of the study was to identify main metabolites of benzylisoquinoline alkaloids from Nelumbinis Plumula after biotransformation by Caco-2 cells.Caco-2 cells were seeded to a 6-well plate and cultured for a period of time until 80%of each well was filled with cells.Then,cell medium was replaced and the norcoclaurine,liensinine,isoliensinine and neferine were respectively added to

Skeletal Muscle Magnetic Resonance Imaging of the Lower Limbs in Late-onset Lipid Storage Myopathy with Electron Transfer Flavoprotein Dehydrogenase Gene Mutations

Background： Lipid storage myopathy （LSM） is a genetically heterogeneous group with variable clinical phenotypes. Late-onset multiple acyl-coenzyme A dehydrogenation deficiency （MADD） is a rather common form of LSM in China. Diagnosis and clinical management of it remain challenging, especially without robust muscle biopsy result and genetic detection. As the noninvasion and convenience, muscle magnetic resonance imaging （MRI） is a helpful assistant, diagnostic tool for neuromuscular disorders. However, the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed. Methods： We assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients, combined with detailed clinical features and gene spectrum. Fat infiltration degree of the thigh muscle was scored while that ofgluteus was described as obvious or not. Associated muscular atrophy was defined as obvious muscle bulk reduction. Results： The mean scores were significantly different among the anterior, medial, and posterior thigh muscle groups. The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group （P 〈 0.00 l）. Moreover, the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group （P 〈 0.01）. About half of the patients displayed fat infiltration and atrophy in gluteus muscles. Of 28 patients, 12 exhibited atrophy in medial and/ or posterior thigh muscle groups, especially in posterior thigh muscle group. Muscle edema pattern was not found in all the patients. Conclusions： Late-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior, posterior, and medial thigh muscle groups, with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment. Our findings also suggest that muscle MRI of lower limbs is a helpful tool in guiding clinical evaluation on late-onset MADD.

A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple AcyI-CoA Dehydrogenase Deficiency

Background： Late-onset multiple acyl-CoA dehydrogenase deficiency （MADD） is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. Methods： We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. Results： After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group （P 〈 0.05）. There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group （P 〈 0.05）. On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that l-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. Conclusions： Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

Rhabdomyolysis and respiratory insufficiency due to the common ETFDH mutation of c.250G>A in two patients with late-onset multiple acyl-CoA dehydrogenase deficiency

To the Editor:Late-onset multiple acyl-CoA dehydrogenase deficiency(MADD)is clinically characterized by a fluctuating or progressive proximal myopathy,exercise intolerance but good responsive to riboflavin.ETFDH mutations are a major cause of late-onset MADD.We analyzed the clinical course,biochemical studies,and muscle magnetic resonance imaging(MRI)and pathologies of two late-onset MADD adult male patients who were misdiagnosed as polymyositis and presented with serious clinical symptoms of rhabdomyolysis and respiratory insufficient after using large dosage of intravenous glucocorticoids.Our current report broadens the clinical phenotypes spectrum of MADD and reminds clinicians to be cautious about using large dosage glucocorticoids in metabolic compromised patients.

A ＂Triple Trouble＂ Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy

Background： Facioscapulohumeral muscular dystrophy （FSHD） is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a ＂complex disease plus＂ patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods： Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification （MLPA）, whole exome sequencing （WES）, and targeted methylation sequencing. Results： The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient＇s mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. Conclusions： The present study described a ＂tripe trouble＂ with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

A novel start codon variant in SMCHD1 from a Chinese family causes facioscapulohumeral muscular dystrophy type 2

To the Editor:Facioscapulohumeral muscular dystrophy type 2(FSHD2)is an epigenetic myopathy caused by variants in genes encoding chromatin regulators,such as SMCHD1:these variants lead to derepression of the D4Z4-encoded DUX4 retrogene in skeletal muscle.[1]The core phenotype of FSHD is progressive muscle weakness in such body parts as the face,shoulder girdle,and upper limbs.Additionally,FSHD may affect the axial muscles and produce bent spine syndrome.Several studies have reported that FSHD2 is associated with causative variants in SMCHD1,[1,2]but to the best of our knowledge,no Chinese FSHD2 patient has been reported.In this report,we presented a Chinese FSHD2 family with D4Z4 hypomethylation and identified a novel start codon variant(c.1 A>G)in SMCHD1.This study was approved by the Ethics Committee for Medical Research of the First Affiliated Hospital of Fujian Medical University(No.2016[17]).Informed consent was obtained from each partici-pant and parent of the participant younger than 18 years of age.

ANTICANCER AGENTS FROM TRADITIONAL CHINESE MEDICINE AND NATURAL PRODUCTS

Chemotherapy is still the effective strategy for treating cancer.It is important to explore anticancer agents from Traditional Chinese Medicine and Natural products.Different cancer cell lines were included in our research,such as HL60,K562,K562/ADR,KB,KBv200 cells.Cell growth inhibition assay,Annexin V-FITC/PI double-staining assay,measurement of reactive