Ultrastructural pathology of human lymphocytes in lysosomal disorders: a contribution to their morphological diagnosis

Abstract

Ultrastructural examination of peripheral lymphocytes was performed in 28 cases of various lysosomal diseases, including infantile, late infantile and juvenile neuronal ceroid-lipofuscinoses (NCL), mucopolysaccharidoses (MPS), juvenile and adult metachromatic leukocystrophies (MLD), GM1-gangliosidosis, one patient with presumed mucolipidosis type IV, mucolipidosis type III, and glycogenosis type II. Based on our own observations on the ultrastructure of lymphocytes in lysosomal disorders, our results may be divided into the following 3 groups: 1. pathological findings with specific inclusions: each type of NCL, presumed mucolipidosis type IV, glycogenosis type II; 2 pathological findings with vacuoles: types I-H, II, III-A and III-B, IV, VI-A and VI-B of MPS, GM1-gangliosidosis; 3. apparently no pathological findings: juvenile and adult MLD, mucolipidosis type III, GM2-gangliosidosis, Gaucher disease. These results led us to conclude that morphological investigations utilizing lymphocytes do not always offer sufficient diagnostic information although easy accessibility favors diagnostic ultrastructural studies of lymphocytes. Such morphological studies should be supplemented by diagnostic biochemical methods.

Immunelectronmicroscopic characterization of T4 and T8 lymphocytes and natural killer cells in neuronal ceroid‐lipofuscinosis

“…Our data on affected CD4+ and CD8+ lymphocytes corroborate results of previous studies of unlabeled lymphocytes in lysosomal storage diseases [Dolman et al, 1980;Ikeda et al, 1982;Kimura and Goebel, 1988;Leroy et al, 1971;Markesbery et al, 19801.…”

Infantile cardiomyopathy and neuromyopathy with ?-galactosidase deficiency

“…In GM1- [4] and GM2- [3] gangliosidoses, intradermal axons have also been shown to harbour osmiophilic dense bodies. Lysosoreal vacuolisation of lymphocytes is pronounced in GMl-gangliosidosis and this lysosomal pathology in lymphocytes clearly distinguishes GMl-gangliosidosis from infantile type 2 glycogenosis where glycogen containing lysosomal inclusions may be found in lymphocytes instead [13]. Lysosoreal vacuolisation of lymphocytes is pronounced in GMl-gangliosidosis and this lysosomal pathology in lymphocytes clearly distinguishes GMl-gangliosidosis from infantile type 2 glycogenosis where glycogen containing lysosomal inclusions may be found in lymphocytes instead [13].…”

PAS‐positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease

“…Glycogen storage in Pompe disease is found in lysosomes throughout the body, including lymphocytes in peripheral blood (de Barsy and Hers 1975; Ikeda et al 1982; Trend et al 1985). Peripheral blood is easy to obtain, and the presence of glycogen-filled vacuoles in lymphocytes can be detected by microscopic inspection of blood films.…”

“…Pompe disease was the only disease in which lymphocytes were reported to stain positively with periodic acid-Schiff (PAS) reagent (Anderson et al 2005). Based on the literature, the presence of PAS-positive lymphocyte vacuoles seems to be specific for Pompe disease (Anderson et al 2005; de Barsy & Hers 1975; Ikeda et al 1982; Straub 2008a; Trend et al 1985), but it was also noted that vacuolated lymphocytes are less frequent in milder forms of the disease compared with the classic infantile form (Anderson et al 2005). In fact, the actual diagnostic value of the test remains unknown unless the frequency in Pompe disease is compared with a control group.…”