The Pathobiochemistry of Gastrointestinal Symptoms in a Patient with Niemann-Pick Type C Disease
- 518 Downloads
The molecular basis of gastrointestinal intolerances in a severe case of Niemann-Pick type C disease was analyzed in an intestinal biopsy specimen. The enzyme activities of intestinal sucrase-isomaltase and maltase-glucoamylase are reduced in the patient, while that of lactase is comparable to the control. The association of SI with lipid rafts is reduced in the patient’s biopsy as a consequence of altered composition of membrane microdomains. As association with lipid rafts influences the intracellular transport and the enzyme activities of sucrase-isomaltase and maltase-glucoamylase, these data explain reduced carbohydrate digestion in the intestinal lumen and delineate the effect of deficient cholesterol and sphingolipid homeostasis in development of gastrointestinal symptoms in NPC patients.
KeywordsLipid Raft Lysosomal Storage Disease Substrate Reduction Therapy Microvillus Membrane NPC1 Gene
The authors would like to thank the patient and her family as well as the Clinic of Pediatrics of the University Hospital Bonn, Germany, for donating the biopsy.
During the course of this work Hadeel Shammas was recipient of a Ph.D. scholarship from the German Academic Exchange Service (DAAD), Bonn, Germany.
- Patterson MC, Vanier MT, Suzuki K et al (2001) Niemann-Pick disease type C: a lipid trafficking disorder. In: Scriver CR, Beaudet AL, Sly WS et al (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3611–3634Google Scholar