Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease.
Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. Through gene hunting in fetal DS brain we found an overexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. This finding was studied further by investigating the activity levels of this key enzyme of carbohydrate metabolism in the brains of patients with DS. PGK activity was determined in five brain regions of nine patients with DS, nine patients with Alzheimer's disease and 14 controls. PGK activity was significantly elevated in the frontal, occipital and temporal lobe and in the cerebellum of patients with DS. PGK activity in corresponding brain regions of patients with Alzheimer's disease was comparable with controls. We conclude that our findings complement previously published data on impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabolism, represented by increased PGK activity, is a specific finding rather than a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, showing overexpressed PGK in DS brains at the transcriptional level early in life. (+info)
Can transvaginal fetal biometry be considered a useful tool for early detection of skeletal dysplasias in high-risk patients?
OBJECTIVE: To evaluate the possibility of an early diagnosis of skeletal dysplasias in high-risk patients. METHODS: A total of 149 consecutive, uncomplicated singleton pregnancies at 9-13 weeks' amenorrhea, with certain menstrual history and regular cycles, were investigated with transvaginal ultrasound to establish the relationship between femur length and menstrual age, biparietal diameter and crown-rump length, using a polynomial regression model. A further eight patients with previous skeletal dysplasias in a total of 13 pregnancies were evaluated with serial examinations every 2 weeks from 10-11 weeks. RESULTS: A significant correlation between femur length and crown-rump length and biparietal diameter was found, whereas none was observed between femur length and menstrual age. Of the five cases with skeletal dysplasias, only two (one with recurrent osteogenesis imperfecta and one with recurrent achondrogenesis) were diagnosed in the first trimester. CONCLUSIONS: An early evaluation of fetal morphology in conjunction with the use of biometric charts of femur length against crown-rump length and femur length against biparietal diameter may be crucial for early diagnosis of severe skeletal dysplasias. By contrast, in less severe cases, biometric evaluation appears to be of no value for diagnosis. (+info)
Comparison of prenatal ultrasound and postmortem findings in fetuses and infants with congenital heart defects.
OBJECTIVE: Detection of congenital heart defects by prenatal ultrasound examination has been one of the great challenges since the investigation for fetal anomalies became part of the routine fetal examination. This prospective study was designed to evaluate the concordance of prenatal ultrasound findings with autopsy examination in a population consisting of both referred women and non-selected pregnant women. DESIGN: Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine and an autopsy performed during the years 1985-94. Results from the ultrasound and autopsy examinations were systematized into categories depending on the degree of concordance. RESULTS: Of 408 infants and fetuses with developmental anomalies, 106 (26%) had congenital heart defects. In 63 (59%) of these 106 cases, the heart defect was the principal reason for the termination of pregnancy or the cause of death. Excluding five cases with a secundum atrial septal defect, there was complete agreement between the ultrasound examination and the autopsy findings in 74 (73%) of 101 cases. In 18 cases, there were minor discrepancies between ultrasound and autopsy findings. The main diagnosis was thus correct in 92 cases (91%). From the first time period (1985-89) to the second (1990-94), the detection rate of all heart defects increased from 48% to 82%. CONCLUSION: This study confirms a good correlation between ultrasound and autopsy diagnoses in fetuses and infants with congenital heart defects. A significant improvement in the detection of heart defects occurred from the first time period to the second and was probably due to increased experience and technical advances. (+info)
Diagnosis of twin reversed arterial perfusion sequence in the first trimester by transvaginal color Doppler ultrasound.
A case of twin reversed arterial perfusion (TRAP) sequence was diagnosed at 12 weeks' gestation using transvaginal color Doppler ultrasound, which demonstrated the presence of retrograde perfusion in the umbilical artery of the abnormal twin. Ultrasound imaging showed a monochorionic-diamniotic twin pregnancy with an inappropriately grown second twin, the morphological evaluation of which revealed an abnormal cephalic pole with acrania, diffuse subcutaneous edema and the presence of cardiac activity in an abnormal heart with a single chamber. (+info)
Amylopectinosis in fetal and neonatal Quarter Horses.
Three Quarter Horses, a stillborn filly (horse No. 1), a female fetus aborted at approximately 6 months of gestation (horse No. 2), and a 1-month-old colt that had been weak at birth (horse No. 3), had myopathy characterized histologically by large spherical or ovoid inclusions in skeletal and cardiac myofibers. Smaller inclusions were also found in brain and spinal cord and in some cells of all other tissues examined. These inclusions were basophilic, red-purple after staining with periodic acid-Schiff (both before and after digestion with diastase), and moderately dark blue after staining with toluidine blue. The inclusions did not react when stained with Congo red. Staining with iodine ranged from pale blue to black. Their ultrastructural appearance varied from amorphous to somewhat filamentous. On the basis of staining characteristics and diastase resistance, we concluded that these inclusions contained amylopectin. A distinctly different kind of inclusion material was also present in skeletal muscle and tongue of horse Nos. 1 and 3. These inclusions were crystalline with a sharply defined ultrastructural periodicity. The crystals were eosinophilic and very dark blue when stained with toluidine blue but did not stain with iodine. Crystals sometimes occurred freely within the myofibers but more often were encased by deposits of amylopectin. This combination of histologic and ultrastructural features characterizes a previously unreported storage disease in fetal and neonatal Quarter Horses, with findings similar to those of glycogen storage disease type IV. We speculate that a severe inherited loss of glycogen brancher enzyme activity may be responsible for these findings. The relation of amylopectinosis to the death of the foals is unknown. (+info)
Whence the arthrogrypotics?
During the course of a nation-wide survey of patients with bone and joint deformities, twenty-six individuals with arthrogryposis multiplex congenita, in the narrow and precise sense of the term, were investigated. No patient was more than twenty-four years of age. However, on a basis of the figures of population, it can be estimated that 21-0 +/- 6-5 older affected individuals should have been encountered. Furthermore, there was a relative excess of younger children. The series was reasonably unbiased, and as arthrogryposis is non-lethal the deficiency of affected adults is an anomalous finding. It is tentatively suggested that arthrogryposis might result from the intra-uterine influence of an unknown environmental agent which has been present in South Africa for only a limited period of time. Detection of this factor could be an important step in the prevention of the disease. (+info)
Neurological morbidity after fetal supraventricular tachyarrhythmia.
BACKGROUND: Fetal tachyarrhythmia is a well-documented entity which, in the absence of pharmacological intervention, may lead to congestive heart failure, fetal hydrops and eventually fetal demise. The success rate of the implemented treatment is generally measured by survival and achievement of control of the arrhythmia. We report on the occurrence of associated cerebral damage in three patients with fetal tachycardia. METHODS: We describe three patients with a history of fetal supraventricular tachyarrhythmia who developed cerebral complications in utero. RESULTS: Two patients had cerebral hypoxic-ischemic lesions and one had hemorrhagic lesions present at birth. They had developed severe congestive heart failure and fetal hydrops secondary to fetal tachyarrhythmia, and there were no other obvious causes for the cerebral pathology. Two of these patients were referred to us antenatally. Therapy was instituted and resulted in control of the tachycardia and resolution of hydrops. The third patient was referred to our clinic shortly after birth because of severe circulatory problems secondary to fetal tachyarrhythmia. CONCLUSION: From these observations, we believe that a fetus with tachyarrhythmia and subsequent hydrops is at increased risk for the development of cerebral complications, due to the circulatory disturbances and sudden changes in heart rate which may lead to fluctuations in cerebral perfusion. This would imply that it is of the utmost importance to aim at immediate and complete control of the heart rate in the treatment of fetal tachyarrhythmia. (+info)
Trisomy 10: first-trimester features on ultrasound, fetoscopy and postmortem of a case associated with increased nuchal translucency.
We report a case of the prenatal diagnosis of trisomy 10 in a fetus presenting with an increased nuchal translucency thickness (5 mm) on a routine first-trimester anomaly scan at 12 weeks' gestation. Multiple abnormalities were diagnosed by ultrasound and fetoscopy. Karyotyping on chorionic villus sampling led to the diagnosis of homogeneous trisomy 10 which was confirmed by in situ hybridization on fetal tissue samples. Postmortem examination confirmed major anatomical malformations, including facial cleft, arthrogryposis of the upper and lower limbs and bilateral diaphragmatic hernia, and also revealed hypoplastic lungs, right renal agenesis and a complex cardiac malformation. Trisomy 10 is an uncommon chromosomal abnormality that is likely to be associated with increased fetal nuchal translucency. This case also emphasizes the value of a detailed anomaly scan in high-risk patients in the first trimester of pregnancy. (+info)