Lysosomal Inclusions in Gastric Parietal Cells in Mucolipidosis Type IV

Abstract

Mucolipidosis type IV (ML-IV) is an autosomal recessive lysosomal storage disease that causes severe neurologic abnormalities. The brain disease is characterized by pigmented cytoplasmic granules in neurons and accumulation of lamellated membrane structures in lysosomes. The gastrointestinal disease in ML-IV was not previously recognized. Clinical examination of 20 patients with ML-IV (age range, 2-23 years) at the National Institutes of Health showed hypergastrinemia and constitutive achlorhydria. Endoscopic biopsy specimens from the gastric fundus, body, and antrum and from the duodenum of four such patients (ages 4, 6, 7, and 22 years) were evaluated histologically and by electron microscopy. Histologically, all gastric fundus and body biopsy specimens showed parietal cells in normal numbers. However, a striking cytoplasmic vacuolization of parietal cells was seen on hematoxylin and eosin stain. Electron microscopy showed the parietal cells to be markedly distended by large lysosomes containing lamellar, concentric, and cystic membranous inclusions. Additionally, chronic atrophic gastritis and enterochromaffin-like (ECL) cell hyperplasia were observed. Foveolar and chief cells in stomach and duodenum biopsy specimens were normal. We conclude that the cytoplasmic lysosomal inclusions in gastric parietal cells is a unique histologic feature of gastric biopsy in ML-IV.

Mitochondrial Aberrations in Mucolipidosis Type IV

“…Brain MRI studies of autopsied cases are consistent with demyelinization, neuronal death, and neuronal loss in the cerebral cortex, basal ganglia, and deep cerebellar and brainstem nuclei (13,14). The degenerative processes in MLIV and in most other lysosomal storage diseases (LSDs) are not limited to brain but also involve skeletal and cardiac muscle, skin, parietal cell, and other tissues (15)(16)(17).…”

“…Although psychomotor retardation is a major consequence of MLIV, TRP-ML1 is ubiquitously expressed, and the degenerative processes are not limited to the brain but are also documented in cornea, retina, skeletal muscles, pituitary gland, and other tissues (11,16,57). Indeed corneal opacification and retinal degeneration are often the presenting symptoms.…”

Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis

“…Cells in various tissues from MLIV patients display large heterogeneous vacuoles similar to those found in cup-5 mutant C. elegans coelomocytes; such structures do not have the characteristic morphology of dense core lysosomes (31)(32)(33)(34). The large vacuoles in cells from MLIV patients contain functional lysosomal hydrolases (35) that could start to degrade the internalized membranes, thus contributing to the heterogeneity in content of the large vacuoles.…”

TRPpathies

“…Patients with MLIV display severe psychomotor retardation and a developmental delay (reviewed in Bach, 2001;Slaugenhaupt, 2002). Other clinical manifestations of MLIV include achloridia and hypergastrinaemia (Schiffmann et al 1998;Lubensky et al 1999). At the cellular level, MLIV is a classic lysosomal storage disease with accumulation, in virtually all tissues and cells, of electron-dense vesicles and membranous inclusions containing phospholipids (Bach & Desnick, 1988;Bargal & Bach, 1989) and gangliosides (Zeigler & Bach, 1986).…”