戊二酸尿症Ⅱ型所致脂肪沉积性肌肉病的诊断与治疗分析

Clinical and biochemical diagnostic and therapeutic survey of seven patients with lipid storage myopathy due to glutaric aciduria type Ⅱ

目的 探讨青少年发病的戊二酸尿症Ⅱ型迟发型的临床特征、诊断与治疗方法。方法 运用气相色谱质谱联用分析对 7例 (男 5例、女 2例 )脂肪沉积性肌肉病患者进行尿有机酸、血液游离脂肪酸测定 ,并通过串联质谱法酯酰肉碱谱分析进一步诊断 ,对戊二酸尿症Ⅱ型迟发型患者的临床与生化特点、诊疗情况进行回顾性研究。结果 患者于 9～ 2 4岁起病 ,主因“进行性无力、肌肉酸疼”来院就诊。 3例患者曾有心悸、胸闷发作 ,3例患者曾有间断嗜睡、浅昏迷发作。患者均有轻度肝肿大 ,4例四肢肌力、肌张力低下 ,肌腱反射消失。患者血清肌酸激酶 (CK)、肌酸激酶同工酶 (CK MB)、乳酸脱氢酶 (LDH)、羟丁酸脱氢酶 (HBDH)均明显增高 ,乳酸、丙酮酸、β 羟丁酸不同程度增高 ,游离肉碱下降 ,6例出现肝功能异常 ,3例曾有低血糖、酮症 ,1例合并轻度代谢性酸中毒、高氨血症。骨骼肌肌肉病理分析均可见明显脂肪沉积 ,2例患者可见部分肌纤维萎缩。 7例患者不饱和脂肪酸癸烯酸 1及十四烯酸 1、中链及长链酯酰肉碱明显增高 ,符合本病诊断。 4例尿 2 羟基戊二酸、3 羟基戊二酸、2 羟基异戊酸、乙基丙二酸增高 ,1例为酮症性二羧基酸尿症。治疗以大剂量核黄素为主 ,治疗初期给予适量左旋肉碱、辅酶Q10 和饮食指导 。

Objective To investigate the clinical and biochemical profiles of the patients with lipid storage myopathy due to late onset glutaric aciduria type Ⅱ. Methods Seven patients (5 boys and 2 girls) with lipid storage myopathy due to glutaric aciduria type Ⅱ were reviewed. The diagnosis was confirmed by urinary organic acid analysis, blood free fatty acid assay with gas chromatography/mass spectrometry (GC/MS) and acylcarnitine profile by tandem mass spectrometry. Their clinical features, laboratory findings, and treatment were studied.Results These previous healthy patients began to develop progressive fatigue, proximal muscular weakness and pain from an age of 9 to 24 years. Five of them had poor appetite and body weight loss. Three had episodic palpitation. Three had recurrent lethargy. All patients had mild hepatomegly. Mild muscular weakness, hypotonia and absence of deep tendon reflexes were found in 4 of them. A marked elevation of serum CK, CK-MB, LDH, HBDH and a slight increase of lactate, pyruvate and β-OH-butyric acid were observed. A decrease of free carnitine was found in 7 patients. Three had hypoglycemia and ketosis. Mild metabolic acidosis and hyperammonemia were found in one boy. Muscle biopsy revealed lipid storage myopathy in all patients. Two of them had muscle fibers atrophy. Dried blood cis-4-decenoic acid (C10∶1), cis-4-tetradecenoic acid (C14∶1), middle chain and long chain acylcarnitine were significantly increased in all patients. An elevated excretion of 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, 2-hydroxyisovaleric acid, and ethylmalonic acid in urine were confirmed in 4 patients. Ketotic dicarboxylic aciduria was found in 1 patient. All of the patients were responded to large dose of riboflavin (100～500 mg/d) significantly. Carnitine, coenzyme Q_(10) supplementation and protein-restricted diet were given for 1 to 2 months as a supporting therapy. Pronounced and rapid clinical and biochemical improvement was observed. All patients went back school or to work after 1 to 3 months therapy. Conclusions The late onset glutaric aciduria type Ⅱ is characterized by lipid storage myopathy. The adolescent patients might respond to riboflavin significantly. Early diagnosis and adequate therapy could contribute a lot to improve the prognosis of the patients. Urinary organic acid analysis and blood free fatty acid assay should be very helpful to the diagnosis.