Considerations in the prenatal assessment of lysosomal enzyme deficiency in eight cases at risk

Some of the factors which are to be considered in the antenatal diagnostic evaluation of lysosomal enzyme levels in cultured amniotic fluid cells are discussed in the light of eight consecutive cases in which the foetuses had a 1 in 4 chance of being homozygous for a lysosomal storage disease. There were 2 possible cases of GM1 gangliosidosis, 2 of neuropathic Gaucher's disease, 1 of Krabbe's disease and 2 of Pompe's disease. Each infant was predicted to be unaffected; the assessments were confirmed to be correct postnatally--7 by enzyme studies. Using a micro technique, 5 of the assessments were available in 28 days or less following amniocentesis. It is concluded that in certain circumstances skin fibroblasts may be used as valid controls and that the variability of assay results strongly militates against the confident assignment of heterozygous status and may cause difficulties in the identification of the homozygote in cases where 'residual' enzyme activity is high; concomitant family studies assist in the resolution of such problems.