Fatal lipid storage myopathy with deficiency of cytochrome-c-oxidase and carnitine

Summary Two newborn female siblings fell ill with apathy, failure of suckling and a generalized progressive muscular hypotonia. Death occured at the age of 7 weeks, obviously caused by impairment of respiratory musculature. Biochemical studies in one child revealed carnitine deficiency especially in skeletal muscle; hepatic encephalopathy was absent. Both children had a generalized hyperaminoaciduria, an unusual finding in primary carnitine deficiency.Besides fatty metamorphosis of the liver, bilateral hydroureters and tubular calcifications of both kidneys, morphological studies showed a generalized lipid storage myopathy which predominated in Type-I-fibres and was accentuated in the muscles of the neck. Enzymehistochemical electron microscopy in longterm frozen muscle demonstrated that cytochrome-c-oxidase activity was absent not only in myopathic but also in most of the morphological unchanged muscle fibres. Only some fibres and endothelial cells displayed normal activity of mitochondria. Biochemically no cytochrome aa₃ (cytochrome-c-oxidase) could be found in skeletal muscle; cytochrome b was almost undetectable. - In newborns with fatal lipid storage myopathy and carnitine deficiency it seems necessary to look for additional defects in the respiratory chain. Enzyme histochemical electron microscopy is a sensitive method in identifying cytochrome-c-oxidase even after a 12 months period of storage.     

Sodium valproate — Induced skeletal myopathy

The authors report a case of skeletal myopathy in a four-year-old boy on long-term sodium valproate therapy for secondary epilepsy due to neurocysticercosis. He presented with clinical features of limb girdle weakness. EMG revealed features of myopathy. Carnitine deficiency due to sodium valproate was suspected and plasma carnitine levels were found to be low. Sodium valproate was withdrawn. L-carnitine supplementation resulted in marked clinical recovery as well as rise in plasma carnitine levels.     

Clinical, pathological, and biochemical studies in a patient with propionic acidemia and fatal cardiomyopathy

A patient diagnosed at 9 months with a milder form of propionic acidemia was functioning at a near normal intellectual level and a normal neurological level at age 8. After 2-week history of feeling "poorly" but functioning normally, she became acutely ill and succumbed to heart failure and ventricular fibrillation in 12 h. At post-mortem the heart was hypertrophied and had low carnitine levels, despite carnitine supplementation and repeatedly normal plasma carnitine levels. The findings in this patient provide a possible mechanism for the cardiac complications that are becoming more apparent in propionic acidemia.     

Serum carnitine levels in patients with homozygous beta thalassemia: a possible new role for carnitine?

Carnitine (-hydroxy--trimethylaminobutyric acid) facilitates the transfer of activated long-chain fatty acids from the cytoplasm to the mitochondria, the site of their -oxidation. Carnitine deficiency results in a reduced usage of fatty acids in energy production and therefore the appearance of clinical symptoms such as myalgia and muscle weakness. In the present study, serum carnitine levels were measured in 45 children and 20 adults with homozygous beta thalassemia. A decrease in serum carnitine levels (total, free and acyl) was found, without any evidence of disorder in the process of mitochondrial -oxidation. The possible cause of this finding could be related to a reduced hepatic carnitine biosynthesis. Conclusion:In patients with homozygous beta thalassemia, the reduction of serum carnitine levels might play an important role in the appearance of muscular dysfunction. It is possible that l -carnitine administration in these patients might improve or even resolve the aforementioned symptom.     

Rett综合征的临床特征及MeCP2的基因型与表型的关系研究

目的 总结Rett综合征(RTT)的临床特点,探讨甲基化CpG结合蛋白2(MeCP2)基因突变型与表型的关系。方法 北京大学第一医院儿科1987年以来诊断的RTT66例,每1～2年对本组患儿进行1次临床随访,并观察左旋肉碱的治疗反应。应用PCR、测序方法对39例患儿进行突变基因分析。结果 患儿3～38个月起病,59例(89％)患儿于7个月～6岁丧失手的功能,66例(100％)患儿1—5岁出现手的刻板动作,56例(85％)患儿11个月～8岁语言完全丧失,21％的患儿于2岁9个月～15岁丧失原已获得的行走能力。头围小、惊厥、呼吸节律异常、咬牙、脊柱侧凸或后凸均很常见。左旋肉碱治疗17例,8周后6例症状改善。39例进行．MeCP2基因分析者中有25例(64％)发现突变,其中2例无义突变C502T(氨基酸改变R168X)患儿均死亡,2例C397T(氨基酸改变R133C)和1例A398T(氨基酸改变R133H)突变者均保留语言。结论 RTI。特征性的表现为头围增长缓慢,手的失用与刻板动作,语言倒退,左旋肉碱可以改善部分患儿的临床症状。MeCP2基因型与表型之间有一定的相关性。     

串联质谱技术在遗传性代谢病高危儿童筛查中的初步应用

目的　开展遗传性代谢病高危儿童筛查检测。方法　临床疑诊遗传性代谢病儿童 10 4例 ,男 77例 ,女 2 7例 ,年龄 (4 8± 4 2 )岁。手指采血 ,滴于专用采血滤纸上。干血滤纸片与含已知量的氨基酸、酰基肉碱同位素内标一起 ,经甲醇萃取 ,盐酸正丁醇衍生后 ,用串联质谱仪分析血片中氨基酸谱和酰基肉碱谱及其浓度。结果　在 10 4例标本中 ,检出阳性标本 10例 (9 6 % ) ,其中酪氨酸血症1例 ,同型胱氨酸血症 1例 ,高鸟氨酸血症 1例 ,甲基丙二酸血症 2例 ,丙酸血症 1例 ,3 羟基 3 甲基戊二酸裂解酶缺乏症 1例 ,中链酰基辅酶A脱氢酶缺乏症 2例 ,酰基肉碱转移酶Ⅱ缺乏症 1例。结论串联质谱技术可检测 30余种遗传性代谢病 ,包括氨基酸代谢紊乱、有机酸代谢紊乱和脂肪酸代谢紊乱性疾病 ,高危遗传性代谢病患儿的筛查有重要价值     

Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds

OBJECTIVE: To evaluate whether the association of antioxidants and anti-inflammatory compounds may be beneficial in treatment of patients with abacterial prostatovesiculoepididymitis (PVE) and elevated seminal leukocyte concentrations. DESIGN: Open, prospective, random study. SETTING: Academic research environment. PATIENT(S): Ninety-eight patients with PVE who had increased seminal leukocyte concentrations (>1 x 10(6) cells/mL).Carnitines (group A; n = 30) or nonsteroidal anti-inflammatory drugs (group B; n = 16) for 4 months; nonsteroidal anti-inflammatory drugs for 2 months, followed by treatment with carnitines for 2 months (group C; n = 26); or nonsteroidal anti-inflammatory treatment given concomitantly with carnitines (group D; n = 26) for 4 months. MAIN OUTCOME MEASURE(S): Semen variables, production of reactive oxygen species, and pregnancy outcome were evaluated before and after treatment and following a 3-month washout period. RESULT(S): Patients in group C had the highest reduction in production of reactive oxygen species associated with increased sperm motility and viability. Groups B and D experienced intermediate effects, and group A experienced the least effect. CONCLUSION(S): Antioxidant treatment with carnitines is effective in patients with abacterial PVE and increased seminal leukocyte concentrations if these patients have been pretreated with nonsteroidal anti-inflammatory drugs.     

Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients

There have been conflicting reports concerning the effect of carnitine supplementation on lipid metabolism in patients on peritoneal dialysis (PD). We investigated several parameters of lipid metabolism in pediatric PD patients supplemented with carnitine. The study included 20 patients receiving PD (treatment group) aged 2–18 years and a matched healthy control group. In the treatment group, baseline triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and apolipoprotein B levels were higher than in the control group. High-density lipoprotein cholesterol, free fatty acid, phospholipids, and apolipoprotein A-I levels were not different from those in the control group. The baseline plasma free carnitine level was lower and acyl-carnitine level was higher in the treatment group. No difference was found between the groups with respect to plasma total carnitine levels. Oral l-carnitine supplementation (50 mg/kg per day for 30 days) led to a significant decrease (from a baseline value of 146.6±51.8 mg/dl to 63.6±22.2 mg/dl, P<0.001) in apolipoprotein B levels, and no significant change in the other lipid parameters of the treatment group. Oral l-carnitine supplementation does not ameliorate the lipid profile in pediatric PD patients, but it causes a significant decrease in apolipoprotein B levels. Hence, carnitine supplementation may be recommended for decreasing apolipoprotein B levels in this patient population.     

肉碱缺乏及其相关疾病的研究进展

肉碱是脂肪β-氧化过程中长链脂酰辅酶A透过线粒体内膜时的转运体,其缺乏导致脂质沉积性肌病、全身肉碱缺乏综合征、心肌病、肥胖、男性不育等疾病.本文主要综述肉碱缺乏的原因及所导致的相关疾病的主要临床表现和治疗手段.     

LOW SERUM CARNITINE CONCENTRATIONS IN HEALTHY CHILDREN WITH IRON DEFICIENCY ANEMIA

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.