Chediak-Higashi syndrome in the cat: prenatal diagnosis by evaluation of amniotic fluid cells.

Chediak-Higashi syndrome (CHS) is an autosomal recessive disease in humans, cats, and 8 other species. The homology of CHS in humans and cats has been demonstrated. Since human CHS is a progressive, serious, and eventually fatal disease, a method for prenatal diagnosis would be desirable. This study was designed to determine whether CHS could be diagnosed prenatally by examination of amniotic fluid cells. The amniotic fluid samples were obtained from CHS and control cat fetuses on the 45th day of gestation and cultures of cells were established. Because the underlying enzyme deficiency in CHS has not been identified, it was necessary to use a secondary manifestation of the syndrome in these studies. The secondary manifestation used was the characteristic enlargement of lysosomes associated with the disease. The lysosomes of these cells were stained by acid phosphatase histochemistry and the diameter of the largest lysosome in each cell was measured by light microscopy with a calibrated ocular micrometer. The diameters of the largest lysosomes in cells of normal fetuses ranged from 0.5 to 7.0 micron (means ranged from 0.9 to 1.8 micron), whereas the diameter of the largest lysosomes in the cells of CHS fetuses ranged from 0.5 to 30 microns (means ranged from 6.4 to 12.8 microns). The approximate t-test for independent samples with unequal variances disclosed that the largest acid phosphatase-positive lysosomes in amniotic fluid cells of CHS cat fetuses were significantly larger than the lysosomes in the cells of normal cat fetuses (P less than 0.0001). This information should, by extrapolation, provide the basis for the prenatal diagnosis of human CHS by amniocentesis.