Deck 21: Lipids: Sphingolipids, Ceramides, and Glycosphingolipids

Question 1

The appearance of which of the following in the blood and/or urine would be predictive of a defect in glycosphingolipid metabolism?

A) gangliosides
B) glucocerebrosides
C) sphingomyelins
D) sphingosine
E) sulfatides

Answer 1

glucocerebrosides

Question 2

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?

A) Gaucher disease
B) Niemann-Pick type C
C) Sandhoff disease
D) Tay-Sachs

Answer 2

Gaucher disease

Question 3

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
B) Gaucher disease
C) G_M2 activator deficiency
D) Krabbe disease
E) Niemann-Pick type C

Answer 3

E
EXPLANATION: 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 phenotypes of NPC disease it has been subdivided into 5 presentation classifications: perinatal, early infantile, late infantile, juvenile, and adult. VSGP is a characteristic neurological manifestation in NPC disease being found in virtually all juvenile and adult cases of the disease

Question 4

The parents of a 7-month-old boy bring their son to the pediatrician because they have noticed that their child has a dull response to outside stimuli. In addition, they note that their child exhibits an exaggerated startle response (sudden extension of arms and legs) to sharp sounds and that he seems to be losing previously acquired motor and mental skills. The symptoms observed in this infant are most indicative of which of the following disorders?

A) Fabry disease
B) Farber lipogranulomatosis
C) Gaucher disease
D) Krabbe disease
E) Tay-Sachs disease

Question 5

The parents of an 18-month-old girl are alarmed at the rapid deterioration in her motor skills and the appearance of an engorged belly. They note that when their daughter tries to follow the movement of an object she thrusts her head in the direction of movement as if she cannot move her eyes from side to side. Physical and laboratory examination reveals hepatosplenomegaly, skeletal lesions, dry scaly skin, and lipid-laden foam cells that have the appearance of wrinkled paper when viewed unde a microscope. What is the most likely diagnosis in
This infant?

A) Fabry disease
B) Gaucher disease
C) Krabbe disease
D) Niemann-Pick disease type B1
E) Tay-Sachs disease

Question 6

An 8-month-old infant is brought to his pediatrician because he has had difficulty in feeding and frequently vomits following feedings. The parents indicate that their son had been able to sit by himself but now is incapable of doing so. Upon examination the doctor notes that the infant has obvious hepatosplenomegaly and is emaciated. Additional physical signs include thin limbs. Examination of his eyes reveals a cherry-red spot in the central part of the retina. Analysis of monocytes indicates the presence of sphingomyelin-rich lipids. The clinical findings in this infant indicate he is suffering from which of the following disorders?

A) fucosidosis
B) Gaucher disease
C) G_M2 activator deficiency
D) Niemann-Pick disease type A1
E) Tay-Sachs disease

Question 7

An adult man suffered from stable angina pectoris for 15 years, during which time there was progressive heart failure and repeated pulmonary thromboembolism. On his death at age 63, autopsy disclosed enormous cardiomyopathy (1100 g), cardiac storage of globotriaosylceramide (11 mg lipid/g wet weight), and restricted cardiocytes. Which of the following lipid storage diseases would result in these clinical findings?

A) Fabry disease
B) Gaucher disease
C) Krabbe disease
D) Niemann-Pick disease type A1
E) Tay-Sachs disease

Question 8

A 4-month-old boy presents with painful progressive joint deformity (particularly the ankles, knees, elbows, and wrists), hoarse crying, and granulomatous lesions of the epiglottis and larynx leading to feeding and breathing difficulty. Biopsy of the liver indicates an accumulation of ceramides. The observed symptoms and the results of the liver biopsy are indicative of which disease?

A) Farber lipogranulomatosis
B) fucosidosis
C) Gaucher disease
D) Metachromic leukodystrophy
E) Sandhoff-Jatzkewitz disease

Question 9

Clinical evidence indicates aspirin is effective in the control of numerous chronic conditions such as atherosclerosis. One of the principal cardiovascular benefits from taking aspirin is due to its ability to reduce the incidence and severity of thrombotic episodes. The anticoagulant effect of aspirin occurs through its ability to inhibit which of the following activities?

A) cyclooxygenase
B) fibrin cross-linking by factor XIIIa
C) phospholipase A₂
D) thrombin binding to activated platelets
E) von Willebrand factor

Question 10

Which of the following occurs in the lipidosis known as Tay-Sachs disease?

A) ganglioside GM2 is not catabolized by lysosomal enzymes
B) phosphoglycerides accumulate in the brain
C) synthesis of a specific ganglioside is decreased
D) synthesis of a specific ganglioside is excessive
E) xanthomas, due to cholesterol deposition, are observed

Question 11

A 2-month-old infant suffering from increased vomiting and diarrhea is seen in the hospital and observed to have significant abdominal distention due to hepatosplenomegaly. Unfortunately, the infant does not survive. Autopsy reveals calcification of the adrenals and massive accumulation of cholesteryl esters and triglycerides in most tissues. Analysis of enzyme activity in fibroblasts and lymphocytes demonstrates a significant acid lipase (cholesteryl ester hydrolase) deficiency. These clinical findings are indicative of which of the following disorders?

A) hyperlipoproteinemia, type I (familial lipoprotein lipase deficiency)
B) I-cell disease (mucolipidosis type II)
C) Maroteaux-Lamy syndrome
D) Sanfilippo syndrome
E) Wolman disease

Question 12

A 42-year-old man presents with hepatomegaly, jaundice, refractory ascites, and renal insufficiency. Peripheral leukocytes exhibit only 20% of normal glucocerebrosidase activity. Which of the following would explain his symptoms?

A) Fabry disease
B) Gaucher disease
C) Krabbe disease
D) Niemann-Pick disease type C2
E) Tay-Sachs disease

Question 13

A 30-month-old child presents with coarse facial features, corneal clouding, hepatosplenomegaly, and exhibiting disproportionate short-trunk dwarfism. Radiographic analysis indicates enlargement of the diaphyses of the long bones and irregular metaphyses, along with poorly developed epiphyseal centers. Other skeletal abnormalities typify the features comprising dystosis multiplex. The child's physical stature and the analysis of bone development indicate the child is suffering from which of the following disorders?

A) Hunter syndrome
B) Hurler syndrome
C) Maroteaux-Lamy syndrome
D) Morquio syndrome type B
E) Sanfilippo disease type A

Question 14

Hypersensitive individuals have IgE to specific antigens (eg, pollen, bee venom) on the surface of their leukocytes (monocytes, macrophages, basophils, eosinophils). When these individuals are challenged with antigen, the antigen-IgE complexes induce synthesis and release of which of the following physiologically potent lipids?

A) arachidonic acid
B) leukotriene B₄
C) platelet-activating factor (PAF)
D) prostaglandin E₂
E) thromboxane A₂ (TXA₂)

Question 15

A 10-year-old girl exhibits the following symptoms: marked hepatomegaly, variceal bleeding, chronic bilateral pulmonary infiltrates, chronic liver disease, hepatic encephalopathy, and only 5% of normal sphingomyelinase activity in peripheral blood leukocytes. What is the most likely diagnosis?

A) Fabry disease
B) Gaucher disease
C) Krabbe disease
D) Niemann-Pick disease type B1
E) Tay-Sachs disease

Question 16

A 12-month-old female infant exhibits severe developmental delay with associated macrocephaly, dysmorphic facies, hypotonia, and hepatosplenomegaly. Clouding of the corneas is not evident. A pebbly ivory-colored lesion is present over the infant's back. The activity of iduronate sulfatase in the plasma is not detectable. These symptoms are indicative of which of the following diseases?

A) Hunter syndrome
B) Hurler syndrome
C) Maroteaux-Lamy syndrome
D) Morquio B syndrome
E) Sanfilippo A syndrome

Question 17

The parents of 6-month-old are alarmed at the apparent regression of their child's pyschomotor skills. The infant has had difficulty in feeding accompanied by recurrent vomiting. Examination reveals a protuberant abdomen with clear hepatosplenomegaly. Extremities are thin and emaciation is apparent. Opthalmologic examination reveals cherry-red maculae. Histochemical examination of the monocytic fraction of the plasma demonstrates the presence of lipid-laden foam cells engorged with sphingomyelin. These findings are indicative of which of the following disorders?

A) fucosidosis
B) Gaucher disease
C) G_M2 activator deficiency
D) Niemann-Pick disease type A1
E) Tay-Sachs disease

Question 18

A 71-year old man was admitted to the hospital after getting very dizzy upon rising from the toilet seat. At that time his pulse was racing and he remembers that his stool looked very different than usual. Over the last 4 or 5 weeks before the incident, the patient self-medicated with highdose ibuprofen 3 times a day to control some pain in his hips. What is the mechanism of action for nonsteroidal anti-inflammatory drugs (NSAIDs) to cause gastrointestinal bleeding?

A) they inhibit arachidonic acid synthesis
B) they inhibit bradykinin synthesis
C) they inhibit cyclooxygenase
D) they inhibit histamine synthesis
E) they promote prostaglandin synthesis

Question 19

Lipoxygenase converts arachidonic acid to biologically active compounds called leukotrienes. Leukotrienes have been implicated in several disease entities, including allergic asthma, where they are presumed to mediate bronchoconstriction. Introducing leukotrienes into an airway would be expected to cause which of the following responses?

A) decreased airway resistance
B) decreased dead space volume
C) increased functional residual capacity
D) increased lung compliance
E) increased total lung capacity

Question 20

You are studying the effects of serum lipoproteins, of the HDL type, on the migration of endothelial cells in culture. Whereas, in one preparation of HDL from wild-type mice you observe significant increases in cell migration, a preparation from a mutant mouse line shows no increase in migration. Knowing the effects of HDL-associated lipids, which of the following lipid classes is most likely to be missing from the mutant mouse HDL preparation?

A) ceramide
B) galactocerebroside
C) G_M2 ganglioside
D) sphingomyelin
E) sphingosine-1-phosphate

Question 21

You are examining cells extracted from a squamous cell tumor of the neck and find that they metabolize palmitic acid at a reduced rate compared to cells isolated from normal tissue in the same region of the neck. Which of the following lipid metabolic enzymes is most likely expressed at reduced levels in the cancer cells relative to normal cells?

A) ceramide synthase 1
B) serine palmitoyltransferase
C) sphingomyelin synthase
D) sphingomyelinase
E) sphingosine kinase

Question 22

Which of the following lipids would most likely result in a reduced response of adipocytes to the actions of insulin?

A) ceramides
B) galactocerebroside
C) GM
1 gangliosides
D) sphingomyelins
E) sphingosine-1-phosphate

Question 23

Studies with a new cell line, derived from a cancerous tumor, reveal that normal responses to apoptotic signals to TNF-α are absent or significantly reduced when compared to normal cells from the same tissue. Further analysis reveals that the cells take up serine and palmitic acid when added to the culture media. Analysis of the levels of sphingosine show that they fluctuate with the same kinetics in both tumor-derived and normal cells. Which of the following sphingolipid metabolizing enzymes is most likely to be missing or significantly reduced in the tumor cells to explain the observations obtained?

A) acid sphingomyelinase
B) ceramidase
C) hexosaminidase A
D) serine palmitoyltransferase
E) sphingosine kinase

Question 24

All sphingolipid storage diseases are the result of an abnormality in which of the following processes?

A) biosynthesis of cerebrosides in the Golgi complex
B) biosynthesis of gangliosides in the ER
C) lipid trafficking among membranes
D) lysosomal catabolism of ceramide lipids
E) processing of glycolipids in the Golgi complex

Question 25

A 7-month-old girl exhibits an exaggerated startle response, has decreased muscle tone, and demonstrates a loss of hearing. Previously attained developmental milestones appear to be disappearingin this infant. Physical and biochemical examinations show cherry-red spots on the retinas of both eyes and a significant reduction in hexosaminidase A activity. A diagnosis of Tay-Sachs disease is made. Which of the following properties of the lipid substrate for the deficient enzyme is the most likely cause of these symptoms?

A) accumulation in cells
B) failure to enter cells
C) failure to form a physiologically required product
D) failure to interact with a cell membrane receptor
E) shunting via minor metabolic pathways