Krabbe disease causing brain damage in West Highland White terriers

Abstract

Two 3-month-old male West Highland White terriers were referred for progressive neurological disease. Histological examination of the central nervous system of the animals euthanized at the owner' request, revealed diffuse, bilateral and symmetrical white matter lesion consisting of varying degrees of demyelination and axonal degeneration. Accumulation of round to ovoid large mononuclear cells was especially observed along the blood vessels in the white matter. These cells were characterized by central or eccentric nuclei and highly eosinophilic, granular and PAS-positive cytoplasm. Stored material was stained with toluidine blue both at pH 4 and pH 11 and exhibited a strong PAC and no PALK activities. Staining for lectins revealed a positivity using Ricinus communis agglutinin-I, Ricinus communis agglutin-II, Triticum vulgaris and Concavalin A. Histochemical evaluation of intracellular material was performed on the kidney and on the liver, too. Ultrastructural investigations allowed to observe the cytoplasmic contents of globoid cells that is an admixture of degraded myelin membranes and different kinds of tubular aggregates. To verify if the two dogs bore the mutation at position 473, a method involving PCR amplification of genomic DNA followed by restriction-digestion was used. The diagnosis of Krabbe's disease was performed based on the clinical evaluation, morphological, histochemical and ultrastructural features.