Chapter 21: Lipids: Sphingolipids, Ceramides, and Glycosphingolipids
The appearance of which of the following in the blood and/or urine would be predictive of a defect in glycosphingolipid metabolism?
Answer B: Glucocerebrosides are only intermediates in the synthesis of complex gangliosides or are found at elevated levels only in disease states such as Gaucher disease, where there is a defect in the catabolism of the complex gangliosides. Thus, the presence of high concentrations of glucocerebrosides in cells such as monocytes and macrophages is indicative of a metabolic defect.
A loss of the ability to correctly process prosaposin into its functional peptides (saposins A, B, C, and D) would most likely result in which of the following disorders of complex glycolipid metabolism?
Answer A: Gaucher disease is characterized by the lysosomal accumulation of glucosylceramide (glucocerebroside) which is a normal intermediate in the catabolism of globosides and gangliosides. Gaucher disease results from defects in the gene encoding the lysosomal hydrolase: acid β-glucosidase, also called glucocerebrosidase. Acid β-glucosidase exists as a homodimer in human cells. In addition to the enzyme itself, an active hydrolytic complex requires an additional activator protein, saposin C. The saposins (A, B, C, and D) are all derived from a single precursor, prosaposin. The mature saposins, as well as prosaposin, activate several lysosomal hydrolases involved in the metabolism of various sphingolipids. Prosaposin is proteolytically processed to saposins A, B, C, and D within lysosomes but also exists as an integral membrane protein not destined for lysosomal entry.
An impaired ability to look upward without raising the head is diagnostic of vertical supranuclear gaze palsy. This defect is associated with which of the following diseases?
A. Familial intrahepatic cholestasis type 1
C. GM2 activator deficiency
Answer E: The characteristic phenotypes associated with “classic” NPC disease are variable hepatosplenomegaly, progressive ataxia, dystonia, dementia, and vertical supranuclear gaze palsy (VSGP). These individuals will present in childhood and death will ensue by the second or third decade. Because of the variable clinical ...