Clinical And Muscle Magnetic Resonance Image Findings In Patients With Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency

Background:Late-onset multiple acyl-coA dehydrogenase deficiency?MADD? is an autosomal recessive genetic and metabolic disorder caused mainly by mutations in ETFA?ETFB? or ETFDH.MADD can be broadly classified as neonatal or delayed onset,defined as episodes beyond the neonatal period?>28 days?.There are two types of neonatal MADD,either?type ?? or no?type ?? congenital abnormalities,and it is usually severe,with hepatomegaly,nonketotic hypoglycemia,metabolic acidosis,hypotonia,and sometimes cardiomyopathy.Late-onset MADD has a large clinical heterogeneity,and the onset of the disease is more common in teenagers or early adulthood.It is mainly manifested by muscle-related symptoms,including limb weakness,fatigue and myalgia.Related research found that patients with late-onset MADD line double lower limbs muscle MRI glutes,back his thigh muscles,legs gastrocnemius and soleus selective symmetrical involvement,the affected muscle group shows fatty degeneration,but the current on patients with late-onset MADD distal limb muscle magnetic resonance imaging?MRI? features are unclear,the study describes a group of patients with late-onset MADD in patients with clinical manifestations and MRI characteristics of lower limb muscles,aims to expand the clinical characteristics of late-onset MADD and explore the lower limb muscle value of MRI in the diagnosis of late-onset MADD.Material and methods:From February 2014 to February 2018,25 patients diagnosed with Late-onset multiple acyl-coA dehydrogenase deficiency?MADD? by muscle biopsy and genetic analysis in the first affiliated hospital of NanChang university were selected.The clinical data of these patients were analyzed.Before treatment,all patients received MRI examination of the thigh and calf muscles,and 8 patients received MRI re-examination after treatment.Results:1.Among the 25 patients with Late-onset MADD,24 were sporadic,and 1 had a family history.The main clinical manifestations are limb proximal muscle weakness,can not tolerate fatigue,chewing difficulties,swallowing difficulties,difficulty raising the head,myalgia.Ten patients developed vomiting after eating greasy food.Chest pain occurred in 3 patients after long distance walking and was relieved after rest.Limb numbness and sensory ataxia occurred in 4 patients.Nine patients had fatty liver disease.A large amount of lipid deposition occurred in the muscle fibers of 25 patients,mainly type 1 muscle fibers.2.All the 25 patients had ETFDH mutations,17 had complex heterozygous mutations,and 8 had single heterozygous mutations.A total of 29 mutations were identified,including 21 previously reported known mutations and 8 new mutations?c.34G> c,c.35-2a > c,c.176-1g > T,c.265₂66delCA,c.542 G > A,c.740G> T,c.1468 + 2T> G,c.1827₁828insCAC?.3.All patients showed signs of edema like changes and fat infiltration on muscle MRI,selectively involving the soleus muscle?SO? but retaining the gastrocnemius muscle?GA? of the leg.Similar signs of selective involvement of the biceps femoris?BFL? were observed in the thigh,with the preservation of the semitendinosus?ST?.The sensitivity and specificity of "SO + / GA-" symbol or "BFL + / ST-" symbol combination for the diagnosis of late onset MADD were 80.0% and 83.5%,respectively.The Logistic regression model supports these findings.The STIR signal of SO and BFL muscle recovered rapidly and the clinical symptoms were also alleviated.Conclusions:1.This study extends the clinical manifestations and gene mutation sites of Late-onset MADD.The clinical manifestations of Late-onset MADD are quite different,mainly manifested as limb proximal muscle weakness,fatigue intolerance,chewing difficulty,swallowing difficulty,dysphagia,dysphagia or slight skeletal muscle extrasystole,including digestive tract symptoms,exertional angina,fatty liver and sensory disturbance.ETFDH gene mutation is the main mutation of ETFDH,and the mutant spectrum is more heterogeneous and there are more new mutations.2.Muscle MRI in delayed MADD shows selective muscle involvement.Specific muscle combinations highlight the diagnostic value of muscle MRI in delayed MADD.All patients with muscle MRI showed signs of edema,change and fatty infiltration,the calf selectively involved in soleus?SO? but retain the gastrocnemius?GA?,in the biceps femoris muscle in his thigh selectively involving?BFL?,but retain the half tendons?ST?,"SO + / GA-" symbol or the "BFL + / ST-" symbol combination of late onset MADD diagnostic sensitivity and specificity of 80.0% and83.5%,respectively.3.The dynamic changes of STIR signal in affected muscles may be considered as biomarkers of therapeutic response.