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Biomedical subjects

I Liebaers

Publications and source records attributed to I Liebaers.

At least 181 records · Page 10Linked to original sources
PubMed1980

Prenatal mucopolysaccharidosis II (Hunter): a pathogenetic study.

A prenatal diagnosis of Mucopolysaccharidosis II (M. Hunter) was made early in a pregnancy at risk in a family with one affected child. An affected fetus was diagnosed on the basis of an abnormal incorporation and degradation of 35SO4 in 35SO4-labeled mucopolysaccharides in cultured amniotic cells. Dermatan sulfate and heparin sulfate concentrations in the supernatant of the amniotic fluid were high. In the aborted fetus, the diagnosis could be confirmed by 35SO4 incorporation studies in the cultured fibroblasts and in cultured brain cells as well as by the deficiency of the specific enzyme activity (iduronide sulfate sulfatase) in the organs of the fetus. beta-Galactosidase was in the low normal range in liver and spleen but significantly reduced in brain. Under electron microscopy, the mesenchymal cells of liver and spleen showed lysosomal storage of material, presumably mucopolysaccharides, in excess of normal. In the neurons of the spinal ganglia and spinal cord, "Zebra bodies" in statu nascendi were observed.

Female↗
PubMed1979

Prenatal monitoring for the Hunter syndrome: the heterozygous female fetus.

An abnormal level of 35S-sulfate labeled mucopolysaccharides was found in cultured amniotic fluid cells from a pregnancy, at risk for the Hunter syndrome, with a female fetal karyotype. Subsequent prenatal analyses suggested heterozygosity for the X-linked Hunter syndrome, and this was confirmed by clonal analysis of fibroblasts of the child after birth. The possible implications of abnormal biochemical results in association with a female karyotype in the prenatal diagnosis of the Hunter syndrome are discussed.

Amniocentesis↗
PubMed1978

Mucopolysaccharidosis II (Hunter disease) with corneal opacities. Report on two patients at the extremes of a wide clinical spectrum.

Clinically visible corneal opacities were observed in a patient with an extremely severe form of mucopolysaccharidosis II. In a second patient with an unusually mild form of mucopolysaccharidosis II, discrete corneal opacities were detected by slit-lamp examination. Thus clear corneae can no longer be regarded as a hallmark of mucopolysaccharidosis II.

Adult↗
PubMed1977

X-linked Hunter syndrome: the heterozygous phenotype in cell culture.

Fibroblast cultures derived from the skin of three Hunter heterozygotes have been examined for iduronate sulfatase deficiency primarily by measurement of [35S]-mucopolysaccharide accumulation in the presence and absence of Hunter corrective factor. For each heterozygote, two populations of clones were observed: normal and enzyme deficient, as predicted by the Lyon hypothesis. However, the phenotype of the uncloned cultures was usually normal, presumably because of cross-correction, even after storage in liquid N2. Mixing experiments indicate that the presence of a majority of cells with the Hunter phenotype may be obscured as the result of correction by the minority population of normal cells in the mixture. Variability in the ability to cross-correct was also demonstrated. The unpredictable behavior of uncloned cultures make them unsuitable for diagnosing the Hunter carrier state.

Cells, Cultured↗
PubMed1977

The Hunter syndrome in females: is there an autosomal recessive form of iduronate sulfatase deficiency?

Profound iduronate sulfatase deficiency, characteristic of the Hunter syndrome, has been found in cultured fibroblasts, serum, lymphocytes, and tissues of two clinically affected girls. The patients are karyotypically normal and have normal fathers; cloning of the mothers' fibroblasts did not reveal the mosaicism expected of carriers of an X-linked disease. Homozygosity for a previously unsuspected autosomal recessive gene for iduronate sulfatase is considered the most likely explanation, although heterozygosity for the X-linked gene and subsequent selection cannot be completely excluded.

Child↗
PubMed1976

Iduronate sulfatase activity in serum, lymphocytes, and fibroblasts--simplified diagnosis of the Hunter syndrome.

A previously described assay for iduronate sulfatase has been adapted for use with serum, lymphocytes, and fibroblasts. The assay also gives a rough measure of iduronidase activity. We have evaluated the procedure for the diagnosis of the Hunter syndrome, for the detection of Hunter heterozygotes, and for the diagnosis of certain other disorders (mucolipidoses II and III and mucopolysaccharidosis I). Hunter patients had 1-2% normal iduronate sulfatase activity in the three sources tested. The serum assay is undoubtedly the method of choice to establish the diagnosis of the Hunter syndrome. Less that 1 ml serum and 3-4 days are required to complete the procedure. Serum could not be used for the detection of iduronidase deficiency diseases, but these could easily be recognized in lymphocyte and fibroblast preparations. The iduronate sulfatase activity of sera from patients with mucolipidoses II and III was elevated 20-fold, but their parents had a normal level of the enzyme. In fibroblasts of patients with mucolipidoses II and III, both iduronate sulfatase and iduronidase activities were markedly decreased. Serum assays were not informative about the Hunter heterozygote status. However, the mean activity in lymphocytes from mothers of Hunter patients was about half of the mean normal activity. A number of obligate heterozygotes had iduronate sulfatase activity so low that they were identifiable as carriers; others, unfortunately, had a clearly normal level. The possibility of carrier detection by the lymphocyte assay needs further development.

Female↗
PubMedDate not supplied

Pyruvate dehydrogenase deficiency: clinical and biochemical diagnosis.

A female neonate with pyruvate dehydrogenase (PDH) deficiency is presented with clinical, radiologic, biochemical, neuropathologic, and molecular genetic data. She was dysmorphic, with a high forehead, lowset ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF and blood. Urinary organic acid profile was compatible with PDH deficiency. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was found within the regulatory phosphorylation site in exon 10. It is postulated that this mutation causes a cerebral form of PDH deficiency. Tissue-specific expression of the disease could be explained by differential X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.

Brain↗
PubMedDate not supplied

Cystic fibrosis, Duchenne muscular dystrophy and preimplantation genetic diagnosis.

Cystic fibrosis (CF) is the most common genetic disease among Caucasians. Duchenne muscular dystrophy (DMD) is one of the most common X-linked genetic disorders. The CF and DMD genes were discovered a few years ago, which provided the possibility for prenatal diagnosis and preimplantation diagnosis of CF and DMD by using specific DNA analysis. In this article, CF, DMD, the process of the identification of the genes of CF and DMD and preimplantation genetic diagnosis are briefly described.

Blastocyst↗
PubMedDate not supplied

The Brussels' experience of more than 5 years of clinical preimplantation genetic diagnosis.

This paper describes the 5 years' experience of preimplantation genetic diagnosis (PGD) at the Brussels Free University. Our first PGD was carried out in February 1993. Up to October 1998, we carried out 183 PGD cycles on fresh cleavage embryos of 92 couples for 25 different conditions. Patients were treated for autosomal recessive (n = 39), autosomal dominant (n = 65) and X-linked recessive (n = 47) monogenic disorders as well as for autosomal structural aberrations (n = 10), sex chromosome numerical and structural aberrations (n = 21) and a combination of the two latter (n = 1). Specific diagnosis was carried out by polymerase chain reaction (n = 108). Fluorescence in-situ hybridization was used for sexing (n = 64) and structural aberrations (n = 11). We transferred 1.6 +/- 1.1 embryos per cycle, resulting in an implantation rate of 12.0% per replaced embryo. Ongoing pregnancies were achieved in 29 cycles, i.e. 23 singletons, five twins and one dichorionic triplet with an acardius acranius. The ongoing pregnancy rates per cycle, per transfer and per couple were 16.4, 19.9 and 31.5% respectively. While 28 ongoing pregnancies resulted in the births of 34 infants, one pregnancy was terminated after misdiagnosis. The results of 24 PGD were confirmed by prenatal diagnosis or after birth while no information was available in four pregnancies. Our series demonstrates that PGD is a feasible technique by which to avoid the birth of genetically affected children to couples at risk.

Adult↗
PubMedDate not supplied

Follow-up of children born after ICSI.

The comparison of outcome of assisted reproductive technology (ART) children and naturally conceived children may be hampered by the difference in characteristics of the infertile patients such as age and genetic risks. Follow-up studies are further hampered by the type of neonatal surveillance protocol, the number of individuals lost to follow-up, the size of the cohort study, and the lack of standardization, for example to define major anomalies. The limited available data on ICSI fetal karyotypes reveal that, in comparison with a general neonatal population, there is: (i) a slight but significant increase in de-novo sex chromosomal aneuploidy (0.6% instead of 0.2%) and structural autosomal abnormalities (0.4% instead of 0.07%); and (ii) an increased number of inherited (mostly from the infertile father) structural aberrations. Available data indicate that in 8319 liveborn ICSI children, the mean percentage who do not originate from singleton pregnancies was 40% (range 32.6-60.8% according to centre). Most multiples are twins, but there are also 4.4% triplets (in one survey 13.2%). This substantial increase in multiple pregnancies must be considered the most important complication of ART. The different percentages of major and minor congenital malformations cannot be compared, but overall the data in large and reliable surveys does not indicate a higher rate of malformations in ICSI children than in naturally conceived children. To date, only three studies have examined the medical and developmental outcome of ICSI children at 1 and 2 years. These do not reveal obvious problems, but in future further comparison of matched cohorts of children and case-control studies are needed before final conclusions can be drawn.

Aneuploidy↗
PubMedDate not supplied

PGD in 47,XXY Klinefelter's syndrome patients.

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using ICSI without PGD, and the conception of one 47,XXY fetus has been reported. In view of the possible risk of an increased gonosome number in the spermatozoa of Klinefelter patients, a safer approach--offering these couples ICSI combined with PGD--has been used, and has resulted in the birth of three healthy children. Couples in which the male suffered from Klinefelter's syndrome were first treated in 1995; these patients were offered ICSI + PGD using FISH technology, notably to enumerate the X and Y chromosomes. ICSI + PGD was performed in 32 cycles of 20 couples with spermatozoa originating from a fresh ejaculate (n = 1), testicular biopsy (n = 21) or frozen-thawed testicular biopsy (n = 10). Normal fertilization occurred in 56.0 +/- 22.4% of the successfully injected oocytes. On day 3 of development, 119 embryos from 29 cycles were of sufficient quality to undergo biopsy and subsequent PGD; a positive result was obtained in 113 embryos. Embryos were available for transfer in 26 cycles, with a mean of 1.6 +/- 0.6 embryos per transfer. Eight pregnancies were obtained, and five resulted in a delivery. A total of 113 embryos from couples with Klinefelter's syndrome was compared with 578 embryos from control couples with X-linked disease where PGD was used to determine gender. A significant fall occurred in the rate of normal embryos for couples with Klinefelter's syndrome (54.0%) compared with controls (77.2%). Moreover, a significantly increased risk of abnormalities was observed for sex chromosomes and autosomes; for each autosome separately, this reached significance level for chromosomes 18 and 21 only. Hence, a cautious approach is warranted in advising couples with non-mosaic Klinefelter's syndrome. Moreover, the use of ICSI + PGD or prenatal diagnosis should be carefully considered.

Embryonic and Fetal Development↗