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.