Prenatal diagnosis of methylmalonic aciduria by analysis of organic acids and total homocysteine in amniotic fluid / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Methylmalonic aciduria (MMA) is the most frequent disease of organic aciduria in China. Various biochemical strategies are followed for the prenatal diagnosis of MMA. However, since fetuses affected by MMA have decreased excretion of methylmalonic acid, the difficulties of prenatal biochemical diagnosis are obvious. Gas chromatography mass spectrometry (GC/MS) and tandem mass spectrometry (ESI/MS/MS) have allowed us to identify the disease in affected fetuses. The aim of this study was to determine the value of analysis of organic acids and total homocysteine in amniotic fluid in prenatal diagnosis of MMA.</p><p><b>METHODS</b>The clinical diagnoses and outcomes of nine probands with MMA and the prenatal diagnoses based on biochemical analysis of nine fetuses at risk for MMA were investigated. Amniotic fluid samples from pregnancies at risk for MMA and metabolically normal pregnancies were obtained at 16 - 24 weeks of gestation. Methylmalonic acid and methylcitric acid were measured by GC/MS, propionylcarnitine was analyzed by ESI/MS/MS, and total homocysteine was determined by fluorescence polarization immunoassay.</p><p><b>RESULTS</b>In two pregnancies, high levels of methylmalonic acid, methylcitric acid, propionylcarnitine, and total homocysteine indicated combined MMA and homocysteinemia in the fetuses. One of the mothers continued pregnancy and received cobalamin supplement as prenatal treatment, and the other terminated her pregnancy. In one pregnancy, significantly elevated levels of methylmalonic acid, methylcitric acid, and propionylcarnitine, and normal level of total homocysteine was found indicating isolated MMA in the fetus; abortion was performed on this case. In the other six pregnancies, all the levels of the above mentioned metabolites were normal suggesting that the fetuses were not affected by MMA. The diagnoses were confirmed after delivery by testing urinary organic acids and plasma total homocysteine.</p><p><b>CONCLUSIONS</b>The metabolic abnormalities of MMA occur early in gestation. The level of total homocysteine in amniotic fluid may be an additional indicator of fetal combined MMA and homocysteinemia. Determination of total homocysteine level in amniotic fluid may become a convenient and reliable method for prenatal diagnosis of the disease.</p>

Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia / 中华儿科杂志

<p><b>OBJECTIVE</b>Methylmalonic aciduria (MMA) is a common one of the congenital disorders of organic acids metabolism. Some of the patients with the disorder are complicated with homocysteinemia. Recently, gas chromatography-mass spectrometry (GCMS) has been used to diagnose MMA in China. However, the diagnosis of the patients with combined MMA and homocysteinemia is often delayed. In this study, the natural history, clinical features and outcome of 57 Chinese patients with combined MMA and homocysteinemia were investigated.</p><p><b>METHODS</b>From 1996 to 2006, 96 MMA patients from 16 provinces or cities were diagnosed in our hospital by urine organic acids analysis using GCMS. Homocysteinemia was found by serum and urine total homocysteine determination using a fluorescence polarization immunoassay.</p><p><b>RESULTS</b>Fifty-seven of the 96 MMA patients (59.4%, 32 males and 25 females) were found to have combined MMA and homocysteinemia. They had markedly increased urine methylmalonic acid, total serum homocysteine (81.5 to 226.5 micromol/L vs. normal range 4.5 to 12.4 micromol/L) and urine homocysteine (79.1 to 414.5 micromol/L vs. normal range 1.0 to 25.0 micromol/L). Thirteen (22.8%) of them presented with symptoms resembled hypoxic-ischemic encephalopathy in the neonatal period. Fourteen (24.6%) patients had the onset at the age of one month to 1 year with mental retardation, vomiting and epilepsy. Nine (15.8%) showed developmental delay, seizures, poor appetite or anemia from the age of 1 to 3 years. Eighteen (31.6%) had psycho-motor degeneration at the age of 6 to 15 years. Among them, 7 patients experienced multiple organ dysfunctions with liver dysfunction, hematuria, renal failure and peripheral neuropathy. Three (5.3%) patients developed progressive mental degeneration, motor disorders and anorexia at the ages of 16, 24 and 34 years. Eleven (19.3%) patients ultimately died; 5 (8.8%) of them were diagnosed postmortem. Forty-six (80.7%) patients were treated with vitamin B12, folic acid, L-carnitine and betaine supplementation and 11 (19.3%) of them recovered completely.</p><p><b>CONCLUSIONS</b>Combined MMA with homocysteinemia is a common form of MMA in China. The clinical spectrum of the patients varies from severe neonatal-onset forms with high mortality to milder forms with adult-onset. Serum or urine total homocysteine analysis is important for the deferential diagnosis of the patients with MMA.</p>

Synthesis and anti-inflammatory activity of N-(4-arylamidophenyl) methanesulfonamide derivatives / 药学学报

<p><b>AIM</b>To study the anti-inflammatory activity of N-(4-arylamidophenyl) methanesulfonamide derivatives.</p><p><b>METHODS</b>The target compounds were synthesized from p-nitroaniline via three steps and were evaluated for anti-inflammatory activity with the model of xylene-induced ear edema in mice.</p><p><b>RESULTS</b>Eleven compounds were obtained and confirmed by IR, 1HNMR and MS. Some compounds were shown to have significant anti-inflammatory activity.</p><p><b>CONCLUSION</b>N-(4-arylamidophenyl) methanesulfonamide showed appreciable anti-inflammatory activity.</p>