Prognostic Value of Left Ventricular Longitudinal Function and Myocardial Fibrosis in Patients With Ischemic and Non-Ischemic Dilated Cardiomyopathy Concomitant With Type 2 Diabetes Mellitus: A 3.0 T Cardiac MR Study.

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. PURPOSE: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. STUDY TYPE: Retrospective cohort. POPULATION: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). FIELD STRENGTH/SEQUENCE: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. ASSESSMENT: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. STATISTICAL TESTS: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). RESULTS: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. CONCLUSIONS: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 5.

Dynamic changes in cardiac morphology, function, and diffuse myocardial fibrosis duration of diabetes in type 1 and type 2 diabetic mice models using 7.0 T CMR and echocardiography.

Background: Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Purpose: Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. Materials and methods: 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. Results: A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). Conclusion: The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.

Case report: An asymptomatic mother with an inborn error of cobalamin metabolism (cblC) detected through high homocysteine levels during prenatal diagnosis.

Background: The most common disorder of the intracellular cobalamin metabolism pathway is the combined methylmalonic acidemia and homocysteinemia, cblC type (cblC). There is a variation in its clinical spectrum ranging from severe neonatal-onset forms that are highly fatal to later-onset forms which are milder. In this study, the first case of an asymptomatic Chinese woman with a defect in congenital cobalamin (cblC type) metabolism at prenatal diagnosis due to elevated homocysteine level is identified. Case presentation: The proband, a male child born to a 29-year-old G1P0 mother, admitted to local hospital with feeding disorder, intellectual disability, seizures, microcephaly, as well as heterophthalmos. The level of the urine methylmalonic was elevated. Equally found were increased blood propionylcarnitine (C3) and propionylcarnitine/free carnitine ratio (C3/C0) and decreased methionine levels. The plasma total homocysteine level was elevated at 101.04 µmol/L (normal < 15 µmol/L). The clinical diagnosis of combined methylmalonic acidemia and homocysteinemia was supported. Four years later, the mother of the boy married again and came to us for prenatal diagnosis exactly 15 weeks after her last menstrual period. Subsequently, there is an increase in the amniotic fluid methylmalonate. The level of the amniotic fluid total homocysteine was marginally high. A considerably elevated amniotic fluid C3 was equally observed. In addition, there is a respective significant increase in the plasma and urine total homocysteine at 31.96 and 39.35 µmol/L. After the sequencing of MMACHC genes, it is found that the boy, a proband carried a homozygous mutation of the MMACHC at c.658_660delAAG. While the boy's mother, she carries two mutations in MMACHC: c.658_660delAAG and c.617G>A. The fetus is a carrier of the MMACHC gene. Following the administration of routine treatment, the mother remained symptom-free in the course of pregnancy, and she gave birth to a healthy boy. Conclusion: Variable and nonspecific symptoms characterized the cblC type of methylmalonic acidemia combined with homocysteinemia. Both biochemical assays and mutation analysis are recommended as crucial complementary techniques.

Luteoloside Exerts Analgesic Effect in a Complete Freund's Adjuvant-Induced Inflammatory Model via Inhibiting Interleukin-1ß Expression and Macrophage/Microglia Activation.

BACKGROUND: Flavonoid monomers are proved to have an anti-inflammatory effect and may also be promising for chronic pain treatment. In the present study, the analgesic effect and the relevant mechanisms of luteoloside, one of the flavonoid monomers, were investigated. METHODS: The analgesic effect of luteoloside was first evaluated in complete Freud's adjuvant induced inflammatory model by von Frey test and Hargreaves test in both male and female mice. The interleukin-1ß levels in plantar tissue, serum, dorsal root ganglion, and the dorsal horn of the spinal cord were determined by enzyme-linked immunosorbent assay or immunofluorescence. The activation of macrophage/microglia was tested by Iba-1 staining. RESULTS: Our data showed that luteoloside exhibited both acute and chronic analgesic phenotypes. Every single dose of luteoloside solution reached the peak transient analgesic effect 2 h after administration and lasted less than 6 h. About 14 consecutive days administration (one dose per day) later, luteoloside showed a sustained analgesic effect which lasted more than 24 h. Celecoxib 20 mg/kg combined with luteoloside 40 mg/kg achieved a similar analgesic effect as celecoxib 40 mg/kg alone. Luteoloside inhibited interleukin-1ß expression in plantar tissue, dorsal root ganglion, the dorsal horn of spinal cord, and serum, after 14 days of continuous administration. Furthermore, our results also showed that the activation of macrophage/microglia in dorsal root ganglions were significantly inhibited 2 h after each single dose in daily luteoloside administration and recovered to a higher level 6 h later. These findings might be involved in the mechanisms of the acute analgesic effect of luteoloside. CONCLUSION: Luteoloside presents an analgesic effect via anti-inflammatory and other mechanisms such as inhibiting the activation of macrophage/microglia.

Clinical Analysis of Postpartum Hemorrhage Requiring Massive Transfusions at a Tertiary Center.

BACKGROUND: The reports on massive transfusions (MTs) in obstetrics have recently been an increasing trend. We aimed to define the clinical features, risk factors, main causes, and outcomes of MTs due to severe postpartum hemorrhage (PPH) and the frequency trends over the past 10 years. METHODS: We retrospectively analyzed the data of 3552 PPH patients who were at ≥28 weeks of gestation in the Obstetric Department of Peking University First Hospital from January 2006 to February 2015. The clinical records of patients receiving MT with ≥5 units (approximately 1000 ml) of red blood cells within 24 h of giving birth were included. The Pearson's Chi-square and Fisher's exact tests were used to compare the frequency distributions among the categorical variables of the clinical features. RESULTS: One-hundred six women were identified with MT over the 10-year period. The MT percentage was stable between the first 5-year group (2006-2010) and the second 5-year group (2011-2015) (2.5‰ vs. 2.7‰, χ2 = 154.85, P = 0.25). Although uterine atony remained the main cause of MT, there was a rising trend for placental abnormalities (especially placenta accreta) in the second 5-year group compared with the first 5-year group (34% vs. 23%, χ2 = 188.26, P = 0.03). Twenty-four (23%) women underwent hysterectomy, and among all the causes of PPH, placenta accreta had the highest hysterectomy rate of 70% (17/24). No maternal death was observed. CONCLUSIONS: There was a rising trend for placental abnormalities underlying the stable incidence of MT in the PPH cases. Placenta accreta accounted for the highest risk of hysterectomy. It is reasonable to have appropriate blood transfusion backup for high-risk patients, especially those with placenta accreta.

Ability of Mn(2+) to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration.

BACKGROUND: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. METHODS: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. RESULTS: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. CONCLUSIONS: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.

A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review.

Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen is defective and causes osseous fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we report a case of type IV osteogenesis imperfecta family and their female member's pregnancy. Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta. The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented. In conclusion, it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the pregnant women with osteogenesis imperfecta, management decision should be made on an individual basis.

[Predictive value of cervical length by transvaginal sonography for preterm pregnancy during mid- and late-trimester of pregnancy].

OBJECTIVE: To study the value of cervical length (CL) by transvaginal sonography in the mid-trimester and late-trimester for the prediction of preterm delivery. METHODS: The CL was measured by transvaginal sonography for 5277 pregnant women between 22 - 24 weeks and 28 - 32 weeks gestation, who were prenatal cared and delivered at the First Hospital of Peking University from June 2008 to November 2009. The pregnancy outcomes were followed, and the relationship between CL and preterm delivery and preterm premature rupture of membrane was studied. RESULTS: (1) The incidence of preterm delivery was 5.4% (289/5370) total, among of them the incidence of therapeutic preterm delivery was 1.7% (93/5370), spontaneously preterm delivery was 1.2% (62/5370), and preterm premature rupture of membrane was 2.5% (134/5370). There are 4 cases (4/5370) who occured late abortion. (2) Excluding the 93 women who had therapeutic preterm delivery, the mean CL of 22 - 24 weeks was (38.8 ± 4.0) mm. The relative risk for preterm delivery when the CL < 30 mm was 5.2, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 13.8. The average CL during 28-32 weeks of gestation was (34.6 ± 4.8) mm, was significantly shorter than that of 22 - 24 weeks (P < 0.05). During this period the relative risk for preterm delivery when the CL < 30 mm was 6.9, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 20.0. (3) A CL < 30 mm as the cut-off value for predicting preterm delivery during 22 - 24 weeks of gestation has only a 3% sensitivity and 19% positive predictive value, but had a 99% specificity and 96% negative predictive value. The sensitivity, positive predictive value, specificity and negative predictive value for a CL < 30 mm as the cut-off value for predicting preterm delivery during 28 - 32 weeks of gestation was 33%, 21%, 95% and 97% respectively. (4) The total number of preterm premature rupture of membrane pregnant women was 134 (2.5%), who had a mean CL of (38.4 ± 4.7) mm during 22 - 24 weeks of gestation, was similar with the women without preterm premature rupture of membrane (PPROM), but during 28 - 32 weeks of gestation the women who occured PPROM had a mean cervical length of (30.6 ± 8.1) mm, and was significantly shorter than that of women without PPROM (34.7 ± 4.6) mm. CONCLUSIONS: (1) CL in 28 - 32 weeks of gestation is significantly shorter than that of in the mid-gestation, but more than 90% of women has a CL ≥ 30 mm. (2) The shorter the CL is, the greater the relative risk of preterm delivery. According to different CL for clinical consulting objective relative risk could be provide. (3) The CL during 28 - 32 weeks of gestation can also predict preterm delivery, the sensitivity is obviously better than that of 22 - 24 weeks of gestation. (4) The CL during 28 - 32 weeks of gestation is valuable for predicting of PPROM.

[Detection of maternal colonization of group B streptococcus in late pregnancy by real-time polymerase chain reaction and its effect on perinatal outcome].

OBJECTIVE: To study the sensitivity of the real-time polymerase chain reaction (RT-PCR) in detecting group B streptococcus (GBS) in late pregnant women and the influence of vaginal/rectal GBS colonization on maternal and neonatal outcomes. METHODS: Microbiological culture and RT-PCR for GBS were both performed for each sample taken from the vagina and rectus in 617 gravidas at 35-37 weeks of gestation, with an average age of 30.1, among which 80 aged over 35. Forty-one out of the 617 women were multiparous and 576 primiparous. The laboratory results were collected and the pregnant outcomes were followed. RESULTS: (1) Out of the 617 gravidas, 21 (3.4%) were GBS positive by culture (all positive in RT-PCR) and 57 (9.2%) were GBS positive by RT-PCR. Thirty-six cases with PCR positive but culture negative results were analyzed by sequencing, and 34 showed GBS positive and 2 negative. (2) The sensitivity and specificity of RT-PCR was 100% (55/55) and 99.6% (560/562) respectively. (3) The average age of GBS positive gravidas was 30 ± 4, without significant difference compared with that of GBS negative women (31 ± 4), P > 0.05. The GBS positive rates were also similar between the primiparas and the multiparous [7.3% (3/41) vs. 9.4% (54/576)], between elderly women and those under the age of 35, and between those women who had abortions over and less than 3 times (all P > 0.05). (4) No significant difference was found in the cesarean section rate between the GBS positive and negative group [54.4% (31/57) vs. 44.6% (250/560), P > 0.05]. (5) Compared with the GBS negative group, the GBS positive group had higher incidence of intrauterine infection [6.6% (37/560) vs. 15.8% (9/57)], postpartum hemorrhage (2.9% vs. 10.5%) and fetal distress (25.9% vs. 38.6%) all P < 0.05, but had similar incidence of premature rupture of membranes [25.0% (140/560) vs. 33.3% (19/57)], preterm birth and meconium-stained amniotic fluid. (6) The neonatal infection rate in the GBS positive group was significantly higher than that of the GBS negative group [29.8% (17/57) vs. 13.2% (77/560), P < 0.05]. One neonate in the GBS positive group developed early-onset severe GBS infection and achieved better outcome under proper treatment. CONCLUSIONS: Maternal GBS carrier at 35-37 weeks of gestation can lead to adverse pregnant outcomes by increasing the incidences of intrauterine infection and neonatal infections. However, RT-PCR could be a routine method to detect GBS status in late pregnant women with its higher sensitivity and specificity.

[Preterm birth and preterm infants in Beijing regional district].

OBJECTIVE: To investigate the incidence and relevant information of preterm birth and the outcomes of preterm infants delivered at various gestational weeks and for different causes. METHODS: Totally 955 women, who ended their pregnancies before term, and 1066 neonates of the previous mothers were enrolled in this survey, among 15,197 deliveries at Peking University First Hospital, Beijing Gynecological and Obstetric Hospital, Women's and Children's Hospital of Haidian District and Peking University Third Hospital, respectively, from December 1(st), 2006 to May 31(st), 2007. RESULTS: (1) Incidence of preterm birth: the overall incidence of preterm birth of the 4 hospitals was 6.3% (955/15 197), and it was 8.1% (125/1549) in Peking University First Hospital, 13.1% (150/1142), which was the highest (P < 0.01), in Peking University Third Hospital, 5.5% (369/6656) in Beijing Gynecological and Obstetric Hospital and 34.0% (311/5850) in Women's and Children's Hospital of Haidian District. The preterm birth rate at the two comprehensive hospitals was significantly higher than that of the two specialized hospitals [10.2% (275/2691) vs 5.4% (680/12 506), P < 0.01]. (2) Gestational weeks at delivery: the incidence of preterm birth before 34 weeks was 28.5% (272/954) and the number changed to 71.5% (682/954) for those preterm deliveries after 34 weeks. However, this number varied among the 4 hospitals. Peking University First Hospital had the highest incidence of preterm birth before 34 weeks (P < 0.05), and the lowest was found in Women's and Children's Hospital of Haidian District (P < 0.01), but no difference was found between Peking University Third Hospital and Beijing Gynecological and Obstetric Hospital. (3) Etiology of preterm birth: preterm premature rupture of membranes (PPROM) accounted for the most proportion of all preterm birth cases, followed by iatrogenic preterm birth and spontaneous preterm birth. But the causes of preterm birth in the 4 hospitals were different. Peking University Third Hospital had a higher incidence of iatrogenic preterm birth than the others (P < 0.01), and Peking University First Hospital had a higher incidence of preterm birth caused by PPROM and lower incidence of spontaneous preterm birth. The first four reasons of iatrogenic preterm birth were preeclampsia (143, 42.0%), fetal distress (58, 17.1%), placenta previa (43, 12.6%) and placenta abruption (33, 9.7%). (4) Neonatal outcomes in different hospitals: the neonatal outcomes were quite different among the 4 hospitals due to different causes and different delivery weeks. The highest neonatal mortality rate was found in Beijing Gynecological and Obstetric Hospital (5.4%, 22/408) compared to that in Women's and Children's Hospital of Haidian District (1.3%, 4/320) and Peking University Third Hospital (0.6%, 1/170) (P < 0.01), but without any difference when compared to that in Peking University First Hospital (2.4%, 3/124) (P > 0.05). (5) Neonatal outcomes at different gestational age: the recovery rate of preterm infants delivered at < 32 weeks was lower than those delivered > or = 32 weeks (P < 0.01), and this number rose to 99.6% in those delivered > or = 34 weeks. More infants delivered < 32 weeks were given up for treatment or died during the perinatal period than those delivered > or = 32 weeks, with the neonatal mortality rate of 22.1% for those delivered at < 32 weeks and only 0.3% for those delivered at > or = 34 weeks (P < 0.01). (6) Neonatal outcomes for various causes: the premature neonatal mortality rate for iatrogenic preterm births was higher than that of PPROM (4.9% vs 1.6%, P < 0.05). But the neonatal recovery rates were similar among the PPROM, spontaneous and iatrogenic preterm birth group (P > 0.05). CONCLUSIONS: Preterm birth is associated with high perinatal mortality rate, especially for those delivered before 32 weeks which would be highlighted in prevention. Reduction of the iatrogenic preterm birth, combined with proper prevention of PPROM, is an important issue in decreasing the prevalence of preterm birth.

[Pregnancy in renal transplant recipient: a case report and review].

In recent years, successful pregnancies in renal transplant women have been reported worldwide. However, pregnancy in renal transplant recipient is relatively rare in China. This paper reported a case of pregnancy 2 years post renal transplant. At the end of 28 weeks' gestation she had abnormal liver and renal function complicated with severe preeclampsia. Literatures were reviewed on considerations about pregnancy in renal transplant women. Maternal and neonatal outcomes can be improved by intensive care during pregnancy, proper immunosupression and timely termination of pregnancy.

Prenatal diagnosis of methylmalonic aciduria by analysis of organic acids and total homocysteine in amniotic fluid.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Prenatal diagnosis of X-linked adrenoleukodystrophy].

OBJECTIVE: To make prenatal dignosis of X-linked adrenoleukodystrophy (ALD) for the prevention of the disease. METHODS: Eighteen amniocenteses were performed on 17 suspected carriers of X-ALD during 18-30 gestation weeks. The very long chain fatty acids (VLCFAs) levels of cultured amniocytes were tested by gas chromatography-mass spectrometry (GC/MS). The plasma VLCFAs levels were measured in 8 of the 18 prenatal diagnosed children when they were born or after abortion. ABCD1 gene mutation analysis was carried out in 8 cases by PCR and sequencing. ALDP of amniocytes was tested by Western blotting in 2 cases from a family, one female, another male, and the VLCFAs of cultured amniocytes were increased in both of them. RESULTS: Among the 18 fetuses, 10 were males and 8 were females. The VLCFAs levels of the cultured amniocytes were increased in 3 males and 4 females. The postnatal plasma VLCFAs were normal in 5 cases with normal VLCFAs levels of amniocytes, and increased in 3 cases with high VLCFAs levels of amniocytes. ABCD1 gene mutations were found in 4 cases with high VLCFAs levels of amniocytes, no mutation was found in other 4 cases with normal VLCFAs levels of amniocytes. ALDP of amniocytes could be detected in the female with high VLCFAs levels of amniocytes, and it could not be detected in the male with high VLCFAs levels of amniocytes. Three male fetuses with high VLCFAs levels of amniocytes were aborted. The others who were born were normal clinically so far. CONCLUSION: The prenatal diagnosis is very important for the prevention of ALD. Amniocyte VLCFAs level analysis combined with ABCD1 gene mutation analysis and ALDP test could make a proper prenatal diagnosis.