一例维生素B12无效型丙二酸血症患儿的护理

丙二酸血症又可称为甲基丙二酸尿症,是一种罕见的有机酸遗传代谢性疾病,属常染色体隐性遗传,婴儿期为其发病高峰年龄[1].是由于甲基丙二酰辅酶A变位酶或其辅酶钴胺素(VitB2,Cb1)的代谢缺陷导致甲基丙二酸等代谢产物在体内蓄积[2].临床表现以神经症状为主,亦可导致多系统损害[3].甲基丙二酸血症患儿临床表现各异,往往易误诊,最见的症状和体征是反复呕吐、嗜睡、惊厥、运动障碍、智力及肌张力低下.本病按治疗效果可分为维生素B12有效型和维生素B12无效型两种.我科于2010年11月收治甲基丙二酸血症患儿一例,现将护理体会总结如下.     

1例甲基丙二酸血症合并脑损伤患儿的护理

甲基丙二酸血症(methylmalonic academia,MMA血症)是一种有机酸代谢异常疾病,为常染色体隐性遗传,活产婴中总发病率为1/4.8万[1],该病根据缺陷酶或辅酶的不同可分为甲基丙二酰辅酶A消旋酶缺乏、甲基丙二酰辅酶A变构酶缺乏,辅酶维生素B12缺乏3种,根据对VB12治疗的反应,前两者合称VB12非反应性MMA血症,后者称为VB12反应性MMA血症,均可导致甲基二酸、丙酸等有机酸蓄积,造成一系列神经系统损害,严重者可因代谢性酸中毒急性发作,出现呕吐、呼吸困难、意识障碍甚至猝死[2].我科2005年12月5日收治了1例VB12反应性MMA血症合并脑损伤的患儿,经治疗护理于2006年1月16日好转出院,现报道如下.     

1例甲基丙二酸血症合并脑损伤患儿的护理

甲基丙二酸血症(methylmalonic academia,MMA血症)是一种有机酸代谢异常疾病,为常染色体隐性遗传,活产婴中总发病率为1/4.8万[1],该病根据缺陷酶或辅酶的不同可分为甲基丙二酰辅酶A消旋酶缺乏、甲基丙二酰辅酶A变构酶缺乏,辅酶维生素B12缺乏3种,根据对VB12治疗的反应,前两者合称VB12非反应性MMA血症,后者称为VB12反应性MMA血症,均可导致甲基二酸、丙酸等有机酸蓄积,造成一系列神经系统损害,严重者可因代谢性酸中毒急性发作,出现呕吐、呼吸困难、意识障碍甚至猝死[2]。我科2005年12月5日收治了1例VB12反应性MMA血症合并脑损伤的患…     

1例新生儿甲基丙二酸血症的饮食护理

甲基丙二酸血症(methyl malonic acidemia,MMA)属于先天性有机酸代谢病,为常染色体隐性遗传,根据酶缺陷的类型分为甲基丙二酰辅酶A变位酶缺陷及其辅酶维生素B12代谢障碍2大类[1]。临床上分为重型、中间型、间歇型、良性型4型。新生儿早期起病的是重型,由于酶缺陷严重,在新生儿生后2~3 d内发病,开始时精神不好、呕吐,以后呼吸急促、昏迷,病情迅速恶化,代谢性酸中毒,用5%碳酸氢钠不能纠正,预后极差,很快死亡[2]。我科成功抢救了1例患甲基丙二酸血症的新生儿,并在治疗同时加强饮食护理,取得了良好的效果,现报告如下。1病例介绍患儿男性,3 d,…     

3例甲基丙二酸血症合并同型半胱氨酸血症患儿的护理

总结3例甲基丙二酸血症合并同型半胱氨酸血症患儿的护理经验.对2例患儿急性期表现为呕吐、四肢抽搐,予补液,观察患儿有无出现脱水症状,预防误吸、跌伤等意外.缓解期,2例VitB12有效型患儿予VitB12维持治疗,避免同时服用苯巴比妥、苯妥英钠、氨基水杨酸及氨基甙类药物,辅以饮食治疗;1例VitB12无效型患儿以饮食控制为主,强调高热量低蛋白饮食;配合康复指导、患儿家长的心理辅导、复查指导和健康教育.目前3例患儿仍在随访中,现在智力水平明显改善,仍予饮食控制,未见并发症,心理状态稳定.     

1例甲基丙二酸血症患儿的护理

甲基丙二酸血症是一种遗传代谢性疾病,属于常染色体隐性遗传,目前为止,全球报告仅100余例.其病理生理的改变是由于甲基丙二酰辅酶A至琥珀辅酶A的代谢障碍,导致体内甲基丙二酰辅酶A、甲基丙二酸、丙酸等有机酸蓄积,造成一系列神经系统损害,严重时可引起酮症酸中毒、低血糖、高血氨、高甘氨酸血症,新生儿、婴幼儿期病死率很高[1].目前该病已发现7种不同的酶缺陷类型,根据对于VitB12试验治疗是否有效,临床分为VitB12有效型与无效型[2].我科于2004年12月7日收治的1例甲基丙二酸血症VitB12有效型患儿,获得满意的治疗护理效果,现报道如下.     

1例新生儿甲基丙二酸血症的饮食护理

甲基丙二酸血症(methyl malonic acidemia,MMA)属于先天性有机酸代谢病,为常染色体隐性遗传,根据酶缺陷的类型分为甲基丙二酰辅酶A变位酶缺陷及其辅酶维生素B12代谢障碍2大类[1].临床上分为重型、中间型、间歇型、良性型4型.新生儿早期起病的是重型,由于酶缺陷严重,在新生儿生后2～3 d内发病,开始时精神不好、呕吐,以后呼吸急促、昏迷,病情迅速恶化,代谢性酸中毒,用5%碳酸氢钠不能纠正,预后极差,很快死亡[2].我科成功抢救了1例患甲基丙二酸血症的新生儿,并在治疗同时加强饮食护理,取得了良好的效果,现报告如下.……     

甲基丙二酸血症临床病理学分析

<正>甲基丙二酸血症(methylmalonic acidemia, MMA)是一种罕见的先天性代谢性疾病，大多为常染色体隐性遗传，由甲基丙二酰辅酶A变位酶(methylmalonyl-CoA mutase, MCM)缺陷或其辅酶钴胺素(维生素B12)代谢缺陷引起^[1]。本研究对1例cb1C型MMA患儿的临床特点及病理尸体解剖特征进行分析，旨在提高医生对本病的认识，进而早期诊断、治疗及监测。     

晚发型甲基丙二酸血症合并高同型半胱氨酸血症家系1例

<正>甲基丙二酸血症或称甲基丙二酸尿症,是先天性有机酸代谢异常中最常见的病种,为常染色体隐性遗传。由于甲基丙二酰辅酶A变位酶或其辅酶钴胺素(维生素B12)代谢缺陷导致甲基丙二酸异常蓄积,造成一系列神经系统损害。本症多在婴幼儿期发病,但1岁后发病的晚发型病例相对较少。现对1个晚发型甲基丙二酸血症合并高同型半胱氨酸血症家系,报道如下。     

婴幼儿甲基丙二酸尿症的MR表现

目的 研究甲基丙二酸尿症婴幼儿患者的头颅MR表现.方法 对17例被确诊为甲基丙二酸尿症的婴幼儿患者(其中9例合并同型半胱氨酸血症)进行头颅常规MRI检查,分析其影像学特点.结果 17例患儿中,14例有明显脑萎缩,7例表现出小脑萎缩,7例患儿有大脑白质脱髓鞘,7例白质髓鞘化程度落后,4例患儿苍白球可见对称性长T2信号,2例患儿合并双侧硬膜下积液.9例合并同型半胱氨酸血症,表现与单纯甲基丙二酸尿症类似.结论 婴幼儿甲基丙二酸尿症的影像学表现主要与代谢异常导致的白质损害有关,了解该病的临床和影像学表现有助于提供诊断的线索.     

Methylmalonyl-CoA mutase activity of leukocytes in variants and heterozygotes of methylmalonic acidemia.

An assay method for the methylmalonyl-CoA mutase of leukocytes obtained from 3 ml of blood was established. The enzyme activity which was measured with or without the in vitro addition of 5'-deoxyadenosylcobalamin was found to be of value for the diagnosis of two variants of methylmalonic acidemia (vitamin B12 responsive and unresponsive), and also for the detection of heterozygotes with the vitamin B12 unresponsive type.     

Organic acid disorders detected by urine organic acid analysis: twelve cases in Thailand over three-year experience

BACKGROUND: Disorders of organic acid (OA) metabolism are generally detected by qualitative analysis of urine organic acids by gas chromatography/mass spectrometry (GC/MS) which was well established in developed countries since 1980s. Confirmation of the diagnosis of organic acid disorders by OA analysis, enzyme analysis and molecular study is a difficult task in developing countries. METHODS: During 2001-2004, we had analysed 442 urine samples in 365 patients and identified 12 cases of organic acid disorders. RESULTS: We identified the following disorders: alkaptonuria (ALK)=1, isovaleric acidemia (IVA)=3, propionic acidemia (PA)=2, methylmalonic acidemia (MMA)=3, glutaric aciduria, type I (GA-I)=1, multiple carboxylase deficiency (MCD)=1, and glutaric acidemia, type II (GA-II)=1. CONCLUSIONS: OA disorders had never been diagnosed in Thailand before, until GC/MS technology was introduced to Thailand in 2001. Urine OA analysis also provided a diagnostic clue to other inborn errors of metabolism including amino acid disorders, urea cycle disorders, disorders of carbohydrate metabolism, and mitochondrial fatty acid oxidation disorders. Since then, we were able to diagnose numerous disorders, which led to prompt treatment and better outcome in our patients.     

Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women

Abstract Background: Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid. Methods: A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined. Results: Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 mumol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio. Conclusions: The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion. Clin Chem Lab Med 2008;46:1265-9.     

Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency

BACKGROUND: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status. METHODS: We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age > or = 60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 deficiency. RESULTS: Low total vitamin B12 (< 148 pmol/L) and low holoTC (< 35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (> 350 nmol/L) and homocysteine (> 13 micromol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%-6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B12 (P < or = 0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentrations of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B12 and/or holoTC within the reference intervals (P < 0.001). CONCLUSIONS: HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.     

Organic acidemias: a methylmalonic and propionic focus

The management of children with organic acidemias (OAs) is limited in nursing literature. This article focuses on the two more common OAs, methylmalonic and propionic acidemias. Literature search was done on PUBMED, CINAHL, OVID, UptoDate, and GeneReview. The benefit of early diagnosis and treatment has been well documented, but many unresolved aspects of care management remain. Patient care is a complex necessitation and a lifelong follow-up for complications. Caring for patients with OA requires that nurses increase their familiarity with metabolic genetics and develop a better understanding of proper medical and nursing management while research continues to determine the most beneficial treatment and long-term care management methods.     

Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography: use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia.

We have developed a sensitive gas-chromatographic method for the determination of methylmalonic acid and other short chain dircarboxylic acids in biological samples. The method is based on the isolation of the short chain dicarboxylic acid fraction by Dowex 3 X 4 column chromatography followed by gas-chromatography analysis of these acids as methyl esters. 2-n-Pentyl-malonic acid is used as an internal standard. With this method, methylmalonic, succinic and methylsuccinic acids were consistently detected and accurately measured in urine and serum from normal subjects; the identity of these acids being verified by mass spectroscopy. The method's sensitivity permitted its used in the prenatal diagnosis of methylmalonic acidemia by measuring methylmalonic acid in urine and amniotic fluid from three pregnant heterozygous women at risk. One affected (vitamin B-12 responsive type) and two unaffected fetuses were correctly diagnosed prenatally as judged by postnatal investigations. The amount of methylmalonic acid in urine and amniotic fluid was distinctly increased (2 to 14 times normal) in the former and consistently normal in the latter two cases during the third trimester of pregnancy. Effect of prenatal therapy with large doses of vitamin B-12 was closely followed in the first case using analyses of multiple maternal urine specimens. Urinary methylsuccinic acid excretion was studied in two cases with isovaleric acidemia. It was normal in a sample from a patient in remission but was increased seven fold over control during an episode of ketoacidosis.     

串联质谱和高效液相色谱-串联质谱二次筛查联合应用于新生儿MMA筛查

目的探讨串联质谱和高效液相色谱-串联质谱二次筛查联合应用在甲基丙二酸血症(MMA)中的筛查价值。方法收集新生儿串联质谱初筛结果中C3、C3/C2、C3/C0单一或多个指标异常的新生儿干血滤纸片标本,用高效液相色谱-串联质谱的方法定量检测原始血片中甲基丙二酸、甲基枸橼酸和高半胱氨酸,对二次筛查后疑似阳性的新生儿进行召回复查,并进行尿气相色谱/质谱检测。临床诊断患儿进一步予以基因检测进行确诊。结果共收集423例C3、C3/C2、C3/C0单一或多个指标异常的新生儿筛查标本,初筛阳性率约为1%,行联合筛查检测结果发现8例标本中甲基丙二酸和同型半胱氨酸表达水平明显升高,召回复查尿气相色谱质谱提示甲基丙二酸轻度升高。结论串联质谱和高效液相色谱-串联质谱联合应用可以提高新生儿MMA筛查的阳性预测值、降低假阳性率,在新生儿遗传代谢病筛查中具有重要价值。     

Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged.

BACKGROUND: Vitamin B(12) deficiency and renal impairment are common in the aged, and therefore the screening test for vitamin B(12) deficiency should not be affected by renal function. Renal impairment has been associated with increased concentrations of plasma total homocysteine and methylmalonic acid, as well as increased total vitamin B(12) and holotranscobalamin concentrations. METHODS: The effect of renal impairment on vitamin B(12)-related biochemical variables was assessed in 1011 aged subjects. RESULTS: Renal function as indicated by serum cystatin C correlated strongly with plasma total homocysteine (r(s)=0.53, p<0.001) and serum methylmalonic acid (r(s)=0.27, p<0.001), but not with serum total vitamin B(12) (r(s)=-0.04, p=0.227) or holotranscobalamin (r(s)=-0.01, p=0.817). CONCLUSIONS: Either total vitamin B(12) or holotranscobalamin rather than homocysteine or methylmalonic acid should be used when screening an aged population prone to renal impairment.     

The clinical evaluation of cobalamin deficiency by determination of methylmalonic acid in serum or urine is not invalidated by the presence of heterozygous methylmalonic-acidaemia

It is well established that accumulation of methylmalonic acid may provide an early clue to the existence of tissue cobalamin (vitamin B12) deficiency. To verify whether methylmalonic acid accumulates in adult heterozygotes for inherited methylmalonic-acidaemia and thereby gives "false" positive test results for cobalamin deficiency, we measured the concentration of methylmalonic acid in serum and its urinary excretion in six patients of three children with severe methylmalonic-acidaemia. We found levels of methylmalonic acid similar to those in normal subjects. In serum, the concentrations of methylmalonic acid ranged from 0.12 to 0.39 mumol/l (reference range: 0.05-0.44 mumol/l). In urine, the values ranged from 1.18 to 2.48 mmol per mol of creatinine (reference range: 0.58-3.56). We conclude that the 2% of carriers of inherited methylmalonic-acidaemia in the general population do not invalidate the usefulness of measurement of methylmalonic acid in serum or urine for the clinical evaluation of cobalamin deficiency.     

Reversible myelopathy in a 34-year-old man with vitamin B12 deficiency

Vitamin B12 deficiency is common, with most patients lacking classic features of advanced severe deficiency. Early diagnosis and treatment prevent severe anemia and irreversible damage to the nervous system. We describe a 34-year-old man with pernicious anemia who presented with clinical and radiologic features of early myelopathy and borderline low serum levels of vitamin B12. Prompt diagnosis based on the measurement of serum methylmalonic acid and treatment with cyanocobalamin injections led to rapid resolution of clinical manifestations and magnetic resonance imaging abnormalities. We review the literature of magnetic resonance imaging in vitamin B12 deficiency myelopathy and discuss the issues relating to diagnosis and early treatment of this potentially reversible condition.