Chediak‐Higashi syndrome: Prenatal diagnosis by fetal blood examination in the feline model of the disease

Abstract

Chediak-Higashi syndrome (CHS) is an autosomal recessive disease of humans, mink, cattle, mice, killer whales, cats, and blue and silver foxes. The disease is characterized by incomplete oculocutaneous albinism, recurrent and severe pyogenic infections, a bleeding tendency secondary to a platelet storage pool deficiency, and enlarged granules in many types of cells. Humans with CHS usually die during childhood. It has been suggested that the prenatal diagnosis of CHS should be possible by the demonstration of enlarged granules in neutrophils of fetal blood. We tested this hypothesis using 20 cat fetuses obtained 18 days at prepartum. Two litters (6 fetuses) were from CHS to CHS matings and four litters (14 fetuses) were from CHS male to heterozygous female matings. Fetuses were identified as CHS or phenotypically normal by histologic examination of the size of melanin granules in the ciliary body and by the size of periodic acid-Schiff-positive granules in renal tubular epithelial cells. The diameter of the peroxidase-positive granules in neutrophils of the 15 CHS fetuses ranged from 0.3 to 3.0 microns whereas those of the five normal fetuses ranged from 0.3 to 1.0 micron. All 20 fetuses were correctly classified as CHS or phenotypically normal. These data indicate that examination of the size of fetal blood neutrophil granules can be used to diagnose CHS prenatally.