Prenatal enzymic diagnosis in 24 pregnancies with risk of Krabbe disease

In 24 pregnancies at risk for Krabbe disease (KD) monitored by amniocentesis in the 15th to 18th week, the amniocytic galactosyl ceramide beta-galactosidase activity was either lower than 11% (n = 12) or higher than 28% (n = 12) of the mean control amniocytic activity (n = 27). For the low activity group, prenatal KD diagnoses were made and the fetuses aborted. In the tissue material available from 11 of them the diagnoses were confirmed enzymatically. Three fetuses were studied electron microscopically and typical tubulo-spicular inclusions were found in the 'pre-globoid cells'. In the children already born from the group with more than 28% of amniocytic lipid beta-galactosidase activity no signs of KD were detectable. In two of the families at risk of KD, four pregnancies followed the monitored ones, but, for obscure reasons, it came to our knowledge only after the birth of these four children; enzymic studies revealed one KD patient and three unaffected children (two of them possibly heterozygous). When comparing the total sample of 12 + 1 KD cases and 12 + 3 unaffected with the theoretical 7:31 ratio for affected/unaffected offspring, a significant prevalence of affected (chi 2 = 6.86; alpha = 0.01) was found.