Mucolipidosis type II with evidence of a novel storage site

Abstract

In a case of infantile mucolipidosis type II (I-cell disease), storage was identified at autopsy in serous-type secretory cells in exocrine pancreas, in the tracheal and sublingual salivary glands and in the chief (zymogenic) cells of the gastric oxyntic glands, suggesting a systemic involvement of this type of secretory cells. The content of specific secretory granules was inversely proportional to the intensity of the storage process. The mucus-producing cells were not affected. The serous glandular system is a novel storage site in I-cell disease. Review of archival material in three further cases confirmed the findings.

Intravenous high-dose enzyme replacement therapy with recombinant palmitoyl–protein thioesterase reduces visceral lysosomal storage and modestly prolongs survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis

“…Pancreatic involvement with lysosomal storage, while it occurs [27], is not often commented upon in relation to enzyme replacement therapy and our model provided an opportunity to demonstrate a positive response to a mannose 6-phosphate- modified enzyme in this tissue. The utilization of the mannose 6-phosphate receptor pathway by the pancreas for lysosomal enzyme targeting can be inferred from exocrine pancreatic involvement in I-cell disease [28] and the high abundance of mannose 6-phosphate receptors in the exocrine pancreas [29–30]. Our data is consistent with these findings and show a particular efficacy of a mannose 6-phosphorylated enzyme in this tissue.…”

Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes

“…These morphological abnormalities are similar to those described in the exocrine pancreas, salivary glands, and gastric chief cells of several MLII patients (Elleder and Martin, 1998). On the basis of our analysis of the acinar cells of the salivary and pancreatic glands of Gnptab −/− mice, we now demonstrate that the vacuolization represents the accumulation of autolysosomes in the mucous and serous cells of these organs.…”

“…By contrast, other cell types exhibit few, if any, morphological alterations, including most cells of the hepatic parenchyma, CNS, and muscle (Kenyon et al , 1973; Martin et al , 1975, 1984; Nagashima et al , 1977). Interestingly, a more recent report described striking vacuolization at a novel site: the serous secretory cells of the pancreas and salivary glands of several infants with MLII (Elleder and Martin, 1998). In that study, the origin of the vacuoles was not explained and the acid hydrolase content of these tissues was not determined.…”

Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice

“…Instead, the predominant lesions in both lines of mice were found in the secretory epithelial cells of several exocrine glands, including the pancreas and the parotid, submandibular salivary, nasal, lacrimal, bulbourethral and gastric glands. We initially believed that mice lacking either the α, β or γ subunits displayed clinical and pathological features that differed substantially from those reported in humans having mutations in orthologous genes, but then found a single report describing similar findings in secretory cells of the exocrine pancreas, salivary glands and gastric chief cells in patients with MLII (Elleder and Martin, 1998). The significance of these earlier findings was not fully appreciated until the pathological phenotypes in knockout mice were published (Gelfman et al, 2007; Vogel et al, 2009).…”