Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies.

From 1989 to 2001, 1,336,145 newborns were screened for biotinidase deficiency in Hungary. Fifty-eight children with the disorder were identified as enzyme-deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.

Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do not influence enzyme activity.

The possibility of using umbilical cord blood for transplantation in several enzyme deficiencies has received increasing attention because of the availability of cord blood, the reduced incidence of post-transplantation complications, such as graft-versus-host disease and the possible accomplishment of good corrective results following transplantation, even in cases of greater HLA disparity. The use of hematopoietic stem cells from unrelated donors is even more highly recommended for the treatment of inherited enzyme deficiencies, because it might reduce the risk of the transplanted cells originating from a carrier of the defect, which might have an inadequate corrective ability. Our study was designed to elucidate whether the gestational age and mode of delivery influences the arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to be similar in the four populations studied (full-term normal spontaneous vaginal delivery, full-term caesarean section, preterm normal spontaneous vaginal delivery and preterm caesarean section). Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery. Moreover, our results are the first published data on normal values for arylsulfatase-A activity in human umbilical cord blood.

[Feto-maternal transfusion following cordocentesis]. / Foetomaternalis transzfúzió cordocentesis kapcsán.

Invasive intrauterine diagnostic procedures may be followed by feto-maternal transfusion. The authors studied the feto-maternal transfusion after cordocentesis. 199 women underwent fetal umbilical cord blood sampling for fetal karyotyping in weeks 15-26. Maternal serum alpha-fetoprotein level was measured before and after the procedure. The data were statistically analysed by multiple regression analysis and the paired and unpaired Student's t-tests. Twenty percent of more maternal serum alpha-fetoprotein level increase was observed in 73 (36.7%) women. Maximum feto-maternal transfusion was 0.684 ml. The average feto-maternal transfusion was 0.045 ml. No fetal exsanguination was observed. Positive correlation was found between bleeding time after cordocentesis (p = 0.0171) and feto-maternal transfusion as well as the duration of the procedure (p = 0.0275) and feto-maternal transfusion. Negative correlation was found between the amount of fetal blood sample and feto-maternal transfusion (p = 0.0431). The puncture site also influenced feto-maternal transfusion. If the cordocentesis has been performed at the insertion of the cord the feto-maternal transfusion was less than at the free floating umbilical cord (p = 0.0293). Higher feto-maternal transfusion was seen more often after transplacental cordocentesis (p = 0.002). These data suggest that fetomaternal transfusion in the indicator of the difficulty of the procedure.