GBE1基因突变型糖原累积病Ⅳ型1例报告

目的探讨GBE1基因突变的糖原累积病Ⅳ型(GSD Ⅳ)患儿的临床特点及其家系的基因突变情况。方法分析1例GSD Ⅳ患儿的临床表现、肝脏病理结果及其父母的全外显子基因测序情况,并进行文献复习。结果患儿,男,1岁10个月,肝脾肿大6月余伴发热7天;肝脏组织病理示慢性肝损伤,不能除外遗传代谢病。全基因外显子检测示患儿存在2种新的GBE1基因的杂合突变,分别为来自父亲的c.1694GA杂合突变(致病性变异)和来自母亲的c.218AG杂合突变(疑似致病性变异)。结合患儿临床表现、病理及基因检测结果确诊为肝型GSD Ⅳ。结论新发现GEB 1基因c. 1694 GA的致病性杂合突变,丰富了GSD Ⅳ型在中国人群的突变谱。     

Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese‐enhanced MRI

Manganese‐enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional‐specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl₂, as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl₂. Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half‐life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T₁‐weighted signal intensities after manganese application, and manganese‐induced memory impairment has been suggested, we assessed hippocampus‐dependent learning as well as possible manganese‐induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn²⁺ application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue. Copyright © 2012 John Wiley & Sons, Ltd.     

Randomized,placebo-controlled trial of ferric carboxymaltose in restless legs syndrome patients with iron deficiency anemia

ObjectiveIntravenous ferric carboxymaltose (FCM) has been shown to be efficacious in treating restless legs syndrome (RLS) symptoms in non-anemic patients. The aim of this study was to evaluate the effectiveness of FCM in treating RLS symptoms in patients who also had an iron deficiency anemia (IDA).MethodsThis is a randomized, double-blinded, placebo-controlled study. Subjects with RLS and IDA were enrolled. Subjects received an infusion of either 1500 mg FCM or placebo in Phase I. The primary outcomes were a change-from-baseline at week six on the International Restless Legs Syndrome Study Group scale (IRLS). Phase II of the study involved long-term (52 weeks) follow-up, for those who responded to treatment in the prior phase, with the potential for further treatment if symptoms returned.ResultsWe enrolled 29 RLS patients with IDA (15 FCM and 14 placebo). At week six post-infusion, FCM compared to placebo group showed significant improvement from baseline in IRLS score (−13.47 ± 7.38 vs. 1.36 ± 3.59). Among secondary outcome variables, quality of sleep showed significant improvement from baseline in the FCM group. 61% of subjects remained off RLS medications at the Phase II, week-52 endpoint. There were no serious adverse events observed in the study.ConclusionThe study showed significant efficacy and safety of FCM 1500 mg treatment both in the short term (6 weeks) and long term (52 weeks) in RLS patients with IDA.     

Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding

Study ObjectiveTo assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding.DesignRetrospective review of electronic medical records.SettingNationwide Children's Hospital in Columbus, Ohio.Participants, Interventions, and Main Outcome MeasuresOne hundred fourteen young women aged 9-19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding.ResultsFifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency.ConclusionIn adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms.     

Iron Deficiency Is Associated with Food Insecurity in Pregnant Females in the United States: National Health and Nutrition Examination Survey 1999-2010

Food-insecure pregnant females may be at greater risk of iron deficiency (ID) because nutrition needs increase and more resources are needed to secure food during pregnancy. This may result in a higher risk of infant low birth weight and possibly cognitive impairment in the neonate. The relationships of food insecurity and poverty income ratio (PIR) with iron intake and ID among pregnant females in the United States were investigated using National Health and Nutrition Examination Survey 1999-2010 data (n=1,045). Food security status was classified using the US Food Security Survey Module. One 24-hour dietary recall and a 30-day supplement recall were used to assess iron intake. Ferritin, soluble transferrin receptor, or total body iron classified ID. Difference of supplement intake prevalence, difference in mean iron intake, and association of ID and food security status or PIR were assessed using χ² analysis, Student t test, and logistic regression analysis (adjusted for age, race, survey year, PIR/food security status, education, parity, trimester, smoking, C-reactive protein level, and health insurance coverage), respectively. Mean dietary iron intake was similar among groups. Mean supplemental and total iron intake were lower, whereas odds of ID, classified by ferritin status, were 2.90 times higher for food-insecure pregnant females compared with food-secure pregnant females. Other indicators of ID were not associated with food security status. PIR was not associated with iron intake or ID. Food insecurity status may be a better indicator compared with income status to identify populations at whom to direct interventions aimed at improving access and education regarding iron-rich foods and supplements.     

Influence of iron oxide nanoparticles (Fe3O4) on erythrocyte photohemolysis via photofrin and Rose Bengal sensitization

BackgroundIron oxide (Fe₃O₄) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that clinically is used in Photodynamic therapy (PDT).Study designThe photosensitivity of PF and Rose Bengal (RB) mixed with (IO-NP) on red blood cells (RBCs) lysis was investigated. Second, Photohemolysis for post-irradiation (delayed) and during irradiation (continuous) with PF, RB and IO-NP combinations at different concentrations was investigated. Third, the photohemolysis rate, relative lysis steepness and power-concentration dependant parameter were evaluated by modeling and fitting the data using Gompertz function and power law.MethodsRBCs were isolated from healthy male human volunteer. Washed cells (7.86 × 10⁶ cells/mm³) were incubated with PF only or with IO-NP for 45 min at 37 °C then irradiated to a range of temperatures (4–41 °C). CPH results were recorded and evaluated using Gompertz function.ResultsThe relative steepness of the photohemolysis curves was approximately independent on light dose for delayed irradiation. The presence of IO-NP increases the rupturing time for 50% of the RBCs. Photohemolysis rate for delayed irradiation using the power law, led to 1.7 and 2.3 power dependence, respectively, for PF only and PF mixed with IO-NP. The power dependence of continuous irradiation measurements showed inverse proportionality for different concentrations of IO-NP combined with 2 μg/ml PF concentration and 1.5 μg/ml for RB concentration.ConclusionPhotosensitization of RBC with PF or RB mixed with IO-NP inhibited rupturing erythrocyte membrane and therefore a consideration should be taken against their combination in clinical applications.     

Mitochondrial membrane protein-associated neurodegeneration: a case report and literature review

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an autosomal recessive disorder caused by mutation in the C19orf12 gene. We report a compound heterozygous c.[32C>T];[205G>A;424A>G] (p.[Thr11Met];[Gly69Arg;Lys142Glu]) Czech patient who manifested with right foot dystonia, impaired handwriting, attention deficit, and signs of iron accumulation on brain MRI. Gradually, he developed dysarthria, spastic-dystonic gait, pedes cavi, and atrophy of leg muscles. Additionally, we report demographic parameters, clinical signs, and allelic frequencies of C19orf12 mutations of all published MPAN cases. We compared the most frequent mutations, p.Thr11Met and p.Gly69ArgfsX10; the latter was associated with younger age at onset and more frequent optic atrophy in homozygotes.