CONSTITUTIVE ACHLORHYDRIA IN MUCOLIPIDOSIS TYPE-IV

Mucolipidosis type IV is an autosomal recessive lysosomal storage dise ase of unknown etiology that causes severe neurological and ophthalmol ogical abnormalities, In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evalua ted 15 consecutive patients, aged 2 to 23 years, over a period of 22 m onths, The finding of iron deficiency in some of the patients led us t o the discovery that all patients but one had markedly elevated blood gastrin levels, None had vitamin B12 deficiency, Gastroscopy in three patients showed normal gross appearance of the mucosa in two patients, 4 and 7 years old, and mucosal atrophy in a 22-year-old. Parietal cel ls were present in normal numbers and contained large cytoplasmic incl usions that were confirmed immunohistochemically to be lysosomal in na ture, Other gastric epithelial cells appeared normal, Parietal cells c ontained very few tubulovesicular membranes, suggesting cellular activ ation, whereas apical canaliculi appeared relatively nonactivated, Bot h subunits of the parietal cell H+/K+-ATPase were present, and both pa rtially colocalized with f-actin at the apical membrane, We conclude t hat patients with mucolipidosis type IV are constitutively achlorhydri c and have partially activated parietal cells, We hypothesize that the defective protein in this disease is closely associated with the fina l stages of parietal cell activation and is critical for a specific ty pe of cellular vacuolar trafficking between the cytoplasm and the apic al membrane domain.