脂质沉积性肌病临床、病理和基因改变特点分析
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摘要
目的报道一例脂质沉积性肌病的临床、病理和基因改变特点。方法先证者为33岁男性,亚急性起病,首发颈肌无力,随后出现咀嚼肌和四肢无力,肌酶明显升高,临床酷似多发性肌炎。血尿有机酸分析未见典型氨基酸、有机酸及脂肪酸代谢病改变,对患者进行了神经电生理、神经肌肉活检以及ETFA、ETFB、ETFDH基因检测。结果骨骼肌病理改变为肌纤维内出现大量脂肪滴沉积,伴随肌纤维坏死、再生。出现小组分布的累及两型的小角状萎缩肌纤维提示伴随神经源性损害。ETFA、ETFB基因检查基本正常,ETFDH基因第3外显子发现c.250G>A(Ala84Thr)杂合突变。结论颈部肌肉无力可能是脂质沉积性肌病早期特点,需要引起重视。尿有机酸筛查正常并不能排除该疾病,进一步的肌肉活检和基因检测是诊断的金标准。多种酰基辅酶A脱氢酶缺乏症患者可以出现周围神经的损害,常染色体隐性遗传疾病相应基因的一个杂合突变难以解释,需要进一步研究。
Objective To summarize the clinical,pathological and genetic charactersitics of a case of riboflavin- responsive lipid myopathy. Methods The patient was a 33 year old man,whose initial syndrome was neck weakness,followed by the weakness of the masticatory muscle and limbs. It resembled the symptoms of polymyositis. Blood and urine organic acid analysis showed no typical changes of amino acids,organic acids and fatty acid metabolism disease. We performed nerve and muscle biopsy and ETFA,ETFB,ETFDH genetic testing. Results Muscle Biopsy study showed markedly increased lipid droplets in muscle fibers,accompanied by muscle fiber necrosis and regeneration. ETFA and ETFB genetic testing were normal,while the ETFDH gene analysis identified a c. 250G > A( Ala84Thr) heterozygous mutation. Conclusion Neck muscle weakness may be the early feature of lipid storage myopathy,which need to pay more attention. Normal urinary organic acid does not exclude the disease,further muscle biopsy and genetic testing are the gold standards for diagnosis. A heterozygous mutation for the autosomal recessive genetic disease is difficult to explain and requires further study.
Objective To summarize the clinical,pathological and genetic charactersitics of a case of riboflavin- responsive lipid myopathy. Methods The patient was a 33 year old man,whose initial syndrome was neck weakness,followed by the weakness of the masticatory muscle and limbs. It resembled the symptoms of polymyositis. Blood and urine organic acid analysis showed no typical changes of amino acids,organic acids and fatty acid metabolism disease. We performed nerve and muscle biopsy and ETFA,ETFB,ETFDH genetic testing. Results Muscle Biopsy study showed markedly increased lipid droplets in muscle fibers,accompanied by muscle fiber necrosis and regeneration. ETFA and ETFB genetic testing were normal,while the ETFDH gene analysis identified a c. 250G > A( Ala84Thr) heterozygous mutation. Conclusion Neck muscle weakness may be the early feature of lipid storage myopathy,which need to pay more attention. Normal urinary organic acid does not exclude the disease,further muscle biopsy and genetic testing are the gold standards for diagnosis. A heterozygous mutation for the autosomal recessive genetic disease is difficult to explain and requires further study.
引文
[1]Burr ML,Roos JC,Ostr AJ.Metabolic myopathies:a guide and update for clinicians[J].Curr Opin Rheumatol,2008,20(6):639-647.
[2]Ohkuma,A,Noguchi S,Sugie H,et al.Clinical and genetic analysis of lipid storage myopathies[J].Muscle Nerve,2009,39(3):333-342.
[3]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[4]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency(MADD)in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250 G>A[J].J Mol Med,2011,89(6):569-576.
[5]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[6]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acylCoA dehydrogenase deficiency[J].J Inherit Metab Dis,2013 Dec 20.[Epub ahead of print]
[7]王韵,赵丹华,洪道俊,等.核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变[J].中华神经科杂志,2011,44(5):309-313.
[8]Liang WC,Ohkuma A,Hayashi YK,et al.ETFDH mutations,CoQ10levels,and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Neuromuscul Disord,2009,19(3):212-216.
[9]管玉青,谢作善,郑卉,等.误诊为多发性肌炎的脂质沉积性肌病-附3例报告[J].中国神经精神疾病杂志,2012,38(2):101-103.
[10]王勤周,焉传祝,吴金玲,等.核黄素反应性脂质沉积性肌病的临床和病理特征[J].临床神经病学杂志,2005,18(5):357-359.
[11]Schiff,M,R Froissart,et al.Electron transfer flavoprotein deficiency:functional and molecular aspects[J].Mol Genet Metab,2006,88(2):153-158.
[12]李务荣,杨旭,赵丹华,等.核黄素反应性脂质沉积性肌病伴感觉共济失调性神经病3例报告[J].中风与神经疾病杂志,2012,29(3),200-203.
[13]吕海东,瞿千千,张燕,等.脂质沉积性肌病的临床、神经电生理和骨骼肌病理分析[J].中风与神经疾病杂志,2012,29(7),598-601.
[14]Zhang W,Miao J,Zhang G,et al.Muscle carnitine deficiency:adult onset lipid storage myopathy with sensory neuropathy[J].Neurol Sci,2010,31(1):61-64.
[15]奚剑英,卢家红,赵重波,等.脂质沉积性肌病35例的临床特点及电子转移黄素蛋白脱氢酶基因突变分析[J].中华神经科杂志,2011,44(5):314-320.
[2]Ohkuma,A,Noguchi S,Sugie H,et al.Clinical and genetic analysis of lipid storage myopathies[J].Muscle Nerve,2009,39(3):333-342.
[3]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[4]Wang ZQ,Chen XJ,Murong SX,et al.Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency(MADD)in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250 G>A[J].J Mol Med,2011,89(6):569-576.
[5]Wen B,Dai T,Li W,et al.Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations[J].J Neurol Neurosurg Psychiatry,2010,81(2):231-236.
[6]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acylCoA dehydrogenase deficiency[J].J Inherit Metab Dis,2013 Dec 20.[Epub ahead of print]
[7]王韵,赵丹华,洪道俊,等.核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变[J].中华神经科杂志,2011,44(5):309-313.
[8]Liang WC,Ohkuma A,Hayashi YK,et al.ETFDH mutations,CoQ10levels,and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Neuromuscul Disord,2009,19(3):212-216.
[9]管玉青,谢作善,郑卉,等.误诊为多发性肌炎的脂质沉积性肌病-附3例报告[J].中国神经精神疾病杂志,2012,38(2):101-103.
[10]王勤周,焉传祝,吴金玲,等.核黄素反应性脂质沉积性肌病的临床和病理特征[J].临床神经病学杂志,2005,18(5):357-359.
[11]Schiff,M,R Froissart,et al.Electron transfer flavoprotein deficiency:functional and molecular aspects[J].Mol Genet Metab,2006,88(2):153-158.
[12]李务荣,杨旭,赵丹华,等.核黄素反应性脂质沉积性肌病伴感觉共济失调性神经病3例报告[J].中风与神经疾病杂志,2012,29(3),200-203.
[13]吕海东,瞿千千,张燕,等.脂质沉积性肌病的临床、神经电生理和骨骼肌病理分析[J].中风与神经疾病杂志,2012,29(7),598-601.
[14]Zhang W,Miao J,Zhang G,et al.Muscle carnitine deficiency:adult onset lipid storage myopathy with sensory neuropathy[J].Neurol Sci,2010,31(1):61-64.
[15]奚剑英,卢家红,赵重波,等.脂质沉积性肌病35例的临床特点及电子转移黄素蛋白脱氢酶基因突变分析[J].中华神经科杂志,2011,44(5):314-320.