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41.
目的探讨新生儿有机酸血症的临床特点和治疗方法。方法回顾性分析24例新生儿有机酸血症的临床资料,采用气相色谱-质谱法(gas chromatography-mass spectrometry,GC/MS)进行尿或血有机酸分析。结果本组患儿症状主要表现为喂养困难(20例),反应减弱(18例),呕吐(7例),呼吸急促(4例),惊厥(7例),肌张力减低(17例)等。血小板减少13例,血气分析提示失代偿性酸中毒7例。10例确诊甲基丙二酸血症患儿接受维生素B12治疗,同时予低蛋白饮食及左旋肉碱治疗。2例死亡。随访8例,时间2个月~3年5个月,4例临床症状完全消失,4例明显好转。结论新生儿有机酸血症的临床表现是非特异性的,可依据GC/MS尿有机酸分析确诊,早期发现和治疗是改善预后的关键。 相似文献
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44.
Effect of PCCB Gene Mutations on the Heteromeric and Homomeric Assembly of Propionyl-CoA Carboxylase
S. Muro B. Prez L. R. Desviat P. Rodríguez-Pombo C. Prez-Cerd S. Clavero M. Ugarte 《Molecular genetics and metabolism》2001,74(4):476
Propionic acidemia is an inherited metabolic disorder caused by deficiency of propionyl-CoA carboxylase, a dodecameric enzyme composed of α-PCC and β-PCC subunits (encoded by genes PCCA and PCCB) that have been associated with a number of mutations responsible for this disease. To clarify the molecular effect associated with gene alterations causing propionic acidemia, 12 different mutations affecting the PCCB gene (R67S, S106R, G131R, R165W, R165Q, E168K, G198D, A497V, R512C, L519P, W531X, and N536D) were analyzed for their involvement in α-β heteromeric and β-β homomeric assembly. The experiments were performed using the mammalian two-hybrid system, which was assayed at two different temperatures to distinguish between mutations directly involved in interaction and those probably affecting polypeptide folding, thus indirectly affecting the correct assembly. Mutations R512C, L519P, W531X, and N536D, located at the carboxyl-terminal end of the PCCB gene, were found to inhibit α-β heteromeric and/or the β-β homomeric interaction independently of the cultivation temperature, reflecting their primary effect on the assembly. Two mutations A497V and R165Q did not affect either heteromeric or homomeric assembly. The remaining mutations (R67S, S106R, G131D, R165W, E168K, and G198D), located in the amino-terminal region of the β-polypeptide, resulted in normal interaction levels only when expressed at the lower temperature, suggesting that these changes could be considered as folding defects. From these results and the clinical manifestations associated with patients bearing the mutations described above, several genotype-phenotype correlations may be established. In general, the temperature-sensitive mutations are associated with a less severe, although variable phenotype. This could correlate with the recent hypothesis that the effect of folding mutations can be influenced by the capacity of the cellular protein quality control machinery, which provides clues to our understanding of the variability of the clinical symptoms observed among the patients bearing these mutations. 相似文献
45.
Canavan disease (CD), a rare recessive autosomal genetic disorder, is characterized by early onset and a progressive spongy
degeneration of the brain involving loss of the axon’s myelin sheath. After a relatively normal birth, homozygous individuals
generally develop clinical symptoms within months, and usually die within several years of the onset of the disease. A biochemical
defect associated with this disease results in reduced activity of the enzymeN-acetyl-l-aspartate amidohydrolase (aspartoacylase) and affected individuals have less ability to hydrolyzeN-acetyl-l-aspartate (NAA) in brain and other tissues. As a result of aspartoacylase deficiency, NAA builds up in extracellular fluids
(ECF) and is excreted in urine. From an analysis of the NAA biochemical cycle in various tissues of many vertebrate species,
evidence is presented that there may be two distinct NAA circulation patterns related to aspartoacylase activity. These include
near-field circulations in the brain and the eye, and a far-field systemic circulation involving the liver and kidney, the
purpose of which in each case is apparently to regenerate aspartate (Asp) in order for it to be recycled into NAA as part
of the still unknown function of the NAA cycle. Based on the authors’ analysis, they have also identified several metabolic
outcomes of the genetic biochemical aspartoacylase lesion. First, there is a daily induced Asp deficit in the central nervous
system (CNS) that is at least six times the static level of available free Asp. Second, there is up to a 50-fold drop in the
intercompartmental NAA gradient, and third, the ability of the brain to perform its normal intercompartmental cycling of NAA
to Asp is terminated, and as a result, the only remaining long-term source of Asp for NAA synthesis is via nutritional supplementation
of Asp or its metabolic precursors. Finally, the authors identify a potential maternal-fetal interaction that may be responsible
for observed normal fetal development in utero, and that provides a rationale for, and suggests how, CD might respond to far-field
nutritional, transplantation, or genetic engineering techniques to alter the course of the disease. 相似文献
46.
Mattijs Out Adriaan Kooy Philippe Lehert Casper A. Schalkwijk Coen D.A. Stehouwer 《Journal of diabetes and its complications》2018,32(2):171-178
Aims
Metformin treatment is associated with a decrease of serum vitamin B12, but whether this reflects tissue B12 deficiency is controversial. We studied the effects of metformin on serum levels of methylmalonic acid (MMA), a biomarker for tissue B12 deficiency, and on onset or progression of neuropathy.Methods
In the HOME trial, 390 insulin-treated patients with type 2 diabetes were treated with metformin or placebo for 52 months. In a post hoc analysis, we analyzed the association between metformin, MMA and a validated Neuropathy Score (NPS).Results
Metformin vs placebo increased MMA at the end of the study (95%CI: 0.019 to 0.055, p = 0.001). Mediation analysis showed that the effect of metformin on the NPS consisted of a beneficial effect through lowering HbA1c (? 0.020 per gram year) and an adverse effect through increasing MMA (0.042 per gram year), resulting in a non-significant net effect (0.032 per gram year, 95% CI: ? 0.121 to 0.182, p = 0.34).Conclusion
Metformin not only reduces serum levels of B12, but also progressively increases serum MMA. The increase of MMA in metformin users was associated with significant worsening of the NPS. These results provide further support that metformin-related B12 deficiency is clinically relevant. Monitoring of B12 in users of metformin should be considered. 相似文献47.
《Hellenic Journal of Cardiology》2020,61(5):330-337
ObjectiveVitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF.MethodsOne hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group.ResultsA total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p < 0.001). This difference remained significant when adjusted for age, sex, vitamin B12, and folate serum levels and kidney function (B = 14.7 (9.6–19.7); p < 0.001). MMA levels were higher in patients with acutely decompensated chronic HF than in those with newly diagnosed acute HF (34.7 ± 10.5 vs. 30.7 ± 7.8 ng/ml; p = 0.036). Correlation analysis revealed significantly negative correlation between MMA and vitamin B12 levels only in patients without comorbidities.ConclusionPatients with HF have elevated MMA levels, independent of age, gender, HF category, or comorbidities, possibly indicating subclinical vitamin B12 deficiency. Further research is needed to investigate subclinical vitamin B12 deficiency in patients with HF and/or to clarify whether MMA constitutes a biomarker of oxidative stress. 相似文献
48.
P. Johannsen K.
stergaard J. Erik Just Christensen M. Worm K. Rasmussen 《European journal of neurology》1995,2(4):357-362
Patients may have neurological symptoms due to cobalamin deficiency in spite of a normal plasma cobalamin level. The aim of the present study was to test if serum-methylmalonic acid (S-MMA) can identify these cobalamin deficient patients. Patients with neurological symptoms consistent with cobalamin deficiency and normal plasma cobalamin had an estimation of S-MMA. If S-MMA was elevated, treatment with by droxycobalamin was offered. The patients were followed for one year in a prospective study with blood tests, clinical assessment and neurophysiological tests. Serum-MMA was above 0.37 μmol/l (+2 SD of normal mean) in 15 out of 134 patients (11.2%) tested. Twelve of these patients were treated with hydroxycobalamin injections. A significant decrease in S-MMA below 0.37 μmol/l was found in 11 patients treated, indicating a functional cobalamin deficiency. Five patients were followed for one year. Documented improvement of neurological symptoms and nerve conduction velocity was shown in three of these patients. Of the remaining two patients treated one did not change and one deteriorated. S-MMA can identify patients with neurological symptoms due to cobalamin deficiency in spite of a normal plasma cobalamin level. 相似文献
49.
B.C.L. Touwen H.J. Huisjes A.D. Jurgens-V.D. Zee M.E.C. Bierman-van Eendenburg M. Smrkovsky A.A. Olinga 《Early human development》1980,4(3):207-228
In order to increase understanding of the origin of neonatal neurological morbidity, the relationship between the obstetrical and neonatal neurological conditions was studied in a 3-year cohort containing 3162 singleton infants. The infants were neurologically examined at term age according to the technique described by Prechtl. Obstetrical data were documented extensively. Prechtl's optimality concept was applied in the analysis. A statistically significant relationship was found between the obstetrical and neo-natal neurological optimality scores. There was no sex difference in the obstetrical optimality, whereas there was in the neurological optimality, to the advantage of the girls. It could be shown that obstetrical conditions such as acidemia, preterm birth and intrauterine growth retardation have a stronger relationship to neurological morbidity when the accompanying obstetrical optimality is lower. In obstetrical practice the application of the optimality concept to obstetrical and neurological data is a helpful complementary refinement. 相似文献
50.
S. Lane Rutledge Michael Geraghty Elizabeth Mroczek David Rosenblatt Ed Kohout 《Pediatric nephrology (Berlin, Germany)》1993,7(1):81-82
We report two patients with methylmalonic acidemia (MMA) in whom renal biopsy demonstrated interstitial nephritis, bringing the total of such reported cases to four. In addition, hypertension, observed in one of our patients, has not been previously reported as the presentation of renal disease in MMA. The etiology of interstitial nephritis in MMA did not appear to be due to urate nephropathy. To date, 15 patients with MMA have been reported with renal complications, including chronic renal failure, making it imperative that children with MMA have their renal status evaluated. 相似文献