1/16. Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family.We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal-5-phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317 --> D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411 --> X). family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used.- - - - - - - - - - ranking = 1keywords = gestation (Clic here for more details about this article) |
2/16. Early prenatal sonographic diagnosis of congenital hypophosphatasia.A pregnant woman of 14 weeks' gestation was sonographically examined due to large-for-dates uterine size. The ultrasound examination showed poor ossification of all bony structures. All limbs were shortened with no evidence of fractures. The echodensity approximated that of the surrounding organs. No acoustic shadowing was observed. Based on these sonographic findings, skeletal dysplasia and short-limb dwarfism were diagnosed, the most likely condition being congenital hypophosphatasia. Early cordocentesis was successfully performed at 15 weeks' gestation to determine fetal alkaline phosphatase concentration. This was undetectable. The prenatal diagnosis of congenital hypophosphatasia was made. After counselling, the woman decided to opt for termination of pregnancy which was performed vaginally. Post-abortion findings confirmed the prenatal diagnosis. To our knowledge, this is the earliest sonographic diagnosis of this condition reported.- - - - - - - - - - ranking = 2.0933371601311keywords = gestation, pregnancy (Clic here for more details about this article) |
3/16. Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648 1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene.We report on a postmortem diagnosis of perinatal lethal hypophosphatasia, an inborn error of metabolism characterized by a liver/bone/kidney alkaline phosphatase (ALP)-related defective bone mineralization due to mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Radiological and pathological studies identified a perinatal lethal hypophosphatasia showing a generalized bone mineralization defect including asymmetry of the cervical vertebral arches in a 22 4 weeks' gestation fetus. Both parents revealed low serum ALP activities supporting the diagnosis. Sequencing analysis of the TNSALP gene showed two heterozygous mutations, 648 1A, a mutation affecting the donor splice site in exon 6, and N400S, a novel missense mutation in exon 11, located near the active site and very close to histidins 364 and 437, two crucial residues of the active site. Sequencing of exons 6 and 11 in the parents showed that 648 1A was from maternal origin and N400S from paternal origin. dna-based prenatal testing in the subsequent pregnancy following a chorionic villous sampling performed at 10 weeks of gestation showed no mutation and a healthy infant was born at term.- - - - - - - - - - ranking = 2.0933371601311keywords = gestation, pregnancy (Clic here for more details about this article) |
4/16. pyridoxine-dependent seizures associated with hypophosphatasia in a newborn.pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.- - - - - - - - - - ranking = 0.093337160131087keywords = pregnancy (Clic here for more details about this article) |
5/16. A successful treatment with pyridoxal phosphate for West syndrome in hypophosphatasia.We report a 2-month-old male with West syndrome associated with infantile hypophosphatasia. The male infant was born at term to a healthy mother after an uneventful pregnancy. He was born by cesarean section because of breech presentation. He was observed to have short extremities, and radiographs were consistent with achondroplasia. The serum alkaline phosphatase level was 2 IU/dL. Intractable tonic seizures developed 2 days after birth, and an electroencephalogram revealed a burst-suppression pattern for the first 2 months of life. The seizures were uncontrollable with conventional antiepileptic drugs. At the age of 2 months, he had a series of infantile spasms, and the electroencephalogram indicated hypsarrhythmia. Treatment with high-dose pyridoxal phosphate eliminated his seizures.- - - - - - - - - - ranking = 0.093337160131087keywords = pregnancy (Clic here for more details about this article) |
6/16. Positive maternal serum triple test screening in severe early onset hypophosphatasia.OBJECTIVES: hypophosphatasia is a rare heritable inborn error of metabolism characterized by a liver/bone/kidney alkaline phosphatase defective bone mineralization due to mutations in the tissue-non-specific alkaline phosphatase (TNS-ALP) gene. To date 128 mutations are described in the TNS-ALP gene located on the short arm of chromosome 1. The clinical presentation of hypophosphatasia is variable ranging from early onset lethal short-limb dwarfism to a late-onset presentation with fractures in childhood or adulthood. methods: We report a pregnancy with a positive maternal serum triple test screening and a post-mortem pathological and molecular diagnosis of perinatal lethal hypophosphatasia. RESULTS: Two heterogeneous missense mutations in the TNS-ALP gene were found, of which one was not previously described. CONCLUSION: This case report adds to the list of fetal malformations found after positive maternal serum triple test screening and reports a previously undescribed mutation in the TNS-ALP gene responsible for hypophosphatasia.- - - - - - - - - - ranking = 0.093337160131087keywords = pregnancy (Clic here for more details about this article) |
7/16. prenatal diagnosis of infantile hypophosphatasia.prenatal diagnosis was attempted in a pregnant Japanese woman whose son had died of infantile hypophosphatasia, using chorionic villi sampled at 10 weeks of gestation. Southern blot analysis of restriction fragment length polymorphism was used as a guide, with cDNA for the human liver-type alkaline phosphatase as a probe, and BclI as a restriction enzyme. The fetus was found to be a heterozygote; the pregnancy was allowed to continue; and the baby born was phenotypically normal.- - - - - - - - - - ranking = 1.0933371601311keywords = gestation, pregnancy (Clic here for more details about this article) |
8/16. First-trimester diagnosis of hypophosphatasia. Importance of gestational age and purity of CV samples.prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villous sample taken in the first trimester. Very low activities of the LBK isoenzymes indicated an affected fetus. Diagnosis was confirmed at 12 weeks of gestation by measurement of LBK isoenzyme activities in fetal bone tissue. In control chorionic villous samples an inverse relation was observed between LBK and placental ALP percentage during gestational age. High LBK ALP activities are observed in decidual tissue. Chorionic villous tissue must not be sampled after 12 weeks of gestation and decidual tissue must be excluded from the sample.- - - - - - - - - - ranking = 7keywords = gestation (Clic here for more details about this article) |
9/16. First trimester diagnosis of hypophosphatasia with a monoclonal antibody to the liver/bone/kidney isoenzyme of alkaline phosphatase.prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villus sample taken in the first trimester. Monoclonal antibodies against the liver/bone/kidney (LBK) and placental isoenzymes of ALP were used, and the bound isoenzymes were quantified by an amplification system. Very low activities of the LBK isoenzyme indicated an affected fetus. Diagnosis was confirmed by ultrasound scan at 15 weeks' gestation, and by ALP measurement in amniotic fluid supernatant and fetal serum.- - - - - - - - - - ranking = 1keywords = gestation (Clic here for more details about this article) |
10/16. Pulmonary hypoplasia in neonatal hypophosphatasia.Morphological, biophysical, and biochemical parameters of lung growth were studied at autopsy on a male infant with hypophosphatasia who died with asphyxia immediately after birth. The lungs were hypoplastic because of a marked decrease in airspace formation but lung maturation was normal for gestational age by all the parameters used. Diaphragmatic development, assessed by weight and fiber measurement, was in keeping with the decreased chest size. The proposed mechanism for this late onset type of pulmonary hypoplasia, attributed to decreased thoracic volume, is correlated with antenatal ultrasonographic observations of normal fetal breathing movements in the affected infant.- - - - - - - - - - ranking = 1keywords = gestation (Clic here for more details about this article) |
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