Vacuolated lymphocytes in type II glycogenosis ?A diagnostic approach?

Abstract

Using electron microscopy, glycogen-filled lysosomes were found in peripheral lymphocytes in 5 cases of the infantile form of glycogenosis type II. In two infants whose blood smears were available, the ultrastructural demonstration of this pathognomonic storage corresponded to well-delineated vacuoles detected by routine light microscopy. Detection of such vacuoles in peripheral lymphocytes by light microscopy and demonstration of glycogen-filled lysosomes by electron microscopy could be a simple and harmless tool for diagnosing the classical form of type II glycogenosis.

The Natural Course of Infantile Pompe’s Disease: 20 Original Cases Compared With 133 Cases From the Literature

“…Patients were hospitalized at median ages of 2.8 months in the Dutch patient group and 4.0 months in literature, 10,11,18 -21,24,26,27,29,30,33,34,36 -38,40 -46,48,51-53,55,61-63,65,68,70,72,74,78,80,82,84,87,89,90,92,95-97,103 and diagnosed at respective ages of 5.3 and 4.5 months. 2,11,18,22,25,27,28,32,41,44,46,47,58,61,66,73,80,83,85,91,93,99 The median time from diagnosis to death was 2 months in both groups. 2,11,18,22,25,27,28,32,41,44,46,61,73,80,83,85,91,93 In the Dutch patient group, death occurred at a median age of 7.7 months.…”

Blood film examination for vacuolated lymphocytes in the diagnosis of metabolic disorders; retrospective experience of more than 2500 cases from a single centre

“…These diseases include Batten's disease (neuronal ceroid lipofuscinosis), [2][3][4] Salla disease, 5 I cell disease, 6 7 b galactosidase deficiency (GM1 gangliosidosis), 8 9 mucopolysaccharidoses, 10 Niemann-Pick disease, 11 fucosidosis, 12 mannosidosis, 13 Wolman's disease, 14 and glycogenoses. 15 Because peripheral blood sampling is performed for a variety of investigations in children with a history suggestive of or consistent with metabolic disease, and because the volume of blood required for such testing is small, screening of blood films for the presence of vacuolated lymphocytes should be considered as a first line investigation in such cases, especially in childhood. There are case reports and small series reporting the variety of specific metabolic diseases that may be associated with vacuolated lymphocytes in peripheral blood films, 2-15 but routine use of this test is not widespread, and no large scale published screening studies are available.…”

Vacuolated PAS‐positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy

“…In Pompe disease, progressive intralysosomal glycogen accumulation involves all tissues throughout the whole body, including lymphocytes in peripheral blood. Presence of glycogen‐filled lysosomes in peripheral lymphocytes detected by electron microscopy and their correspondence to vacuoles in the same cells observed by light microscopic inspection of blood films in two patients suffering from Pompe disease has been reported since 1977 (von Bassewitz et al, ). Vacuolated lymphocytes were identified in blood films of patients with Pompe disease (both classic infantile and adulthood form), and other diseases such as juvenile Batten's disease, GM1 gangliosidosis, galactosialidosis, mucopolysaccharidosis, and I‐cell disease.…”

“…More recently, measurement of residual GAA activity on dried blood spots (DBS), as well as detection by light microscopy of glycogen-filled vacuoles in lymphocytes on blood smears, have been proposed as screening methods to identify LOPD patients in a series of patients at risk of myopathy (Hagemans et al, 2010;Muntoni, Zafeiriou, Jimenez, Reuser, & Sewry, 2005;Musumeci et al, 2016;von Bassewitz, Bremer, Bourgeois, Grobe, & Stoermer, 1977). However, sensitivity and specificity of DBS are not reported, while high sensitivity and specificity of PAS-positive lymphocytes vacuoles count in distinguishing Pompe patients from healthy controls has been described (Hagemans et al, 2010).…”