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Free STEP1 Exam Braindumps (page: 80)

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PDF with 845 Questions

A 28-year-old man has the following symptoms: diffuse grayish corneal opacities, anemia, proteinuria, and hyperlipemia. Renal function is normal and serum albumin level is only slightly elevated. Plasma triglycerides and unesterified cholesterol levels are elevated, as are levels of phosphatidylcholine. These symptoms are indicative of which lipoproteinassociated disorder?

  1. Bassen-Kornzweig syndrome
  2. familial hypercholesterolemia (FH)
  3. familial hypertriacylglycerolemia
  4. familial lecithin-cholesterol acyltransferase (LCAT) deficiency
  5. Wolman disease

Answer(s): D

Explanation:

Two familial syndromes directly involve defects in LCAT. Familial LCAT deficiency is characterized by near complete absence of the enzyme activity from the plasma. Fish eye disease is characterized by an absence of LCAT activity toward high-density lipoproteins (HDLs) but presence of activity toward LDLs.
Clinical features of familial LCAT deficiency include corneal opacities, anemia, and proteinuria. Due to the lack of LCAT activity, the plasma level of esterified cholesterol is lower than normal and phosphatidylcholine (the principal source of fatty acid for esterification to cholesterol) levels are higher than normal. The profile of all classes of plasma lipoproteins in patients with familial LCAT deficiency is abnormal. Bassen-Kornzweig syndrome (choice A), also identified as abetalipoproteinemia, is due to a defect in apo B expression. Clinical symptoms include retinitis pigmentosa, ataxic neuropathy, and erythrocytes that appear thorny (acanthocytosis). FH (choice B) is characterized by reduced LDL clearance, which leads to severe hypercholesterolemia. Major clinical symptoms are arterial deposition of LDL-cholesterol, which leads to atherosclerosis and coronary artery disease. Deposition of LDL- cholesterol is also seen in tendons and skin resulting in xanthomas. Familial hypertriacylglycerolemia (choice C), also identified as hyperlipoproteinemia type IV, is a form of LPL deficiency. The defect leads to increased levels of circulating VLDLs and is associated with glucose intolerance and hyperinsulinemia. This disorder is frequently associated with Type II diabetes. Wolman disease (choice E) is cholesterol ester storage disease that leads to massive accumulation of cholesteryl esters and triglycerides in most tissues.
This disease is almost always fatal within the first year of life and thus would not be present in a 28-year- old.



A 23-year-old man sees his physician to ask about the recent appearance of several large closely spaced bumps on his elbows. Suspecting that these are fatty eruptions, the physician tests the man's blood for lipid, cholesterol, and lipoprotein levels. Results show elevated cholesterol and triglycerides and the presence of a variant form of very low-density lipoprotein (VLDL) identified as beta-migrating VLDL (- VLDL). Amore careful analysis of the biochemical properties of the apoproteins associated with the beta- VLDL particles identifies a form of apo E that has a more negative charge than apo E from normal individuals. These results indicate the individual is afflicted with which of the following hyperlipoproteinemias?

  1. type I (familial LPL deficiency)
  2. type II (FH)
  3. type III (dysbetalipoproteinemia)
  4. type IV (familial hypertriglycerolemia)
  5. Wolman disease

Answer(s): C

Explanation:

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) results from a genetic variant in the apo E gene that causes poor interaction of chylomicron remnants and VLDLs with the apo E receptor. This results in the presence, in the serum, of beta-migrating VLDL (- VLDLs), which are cholesterol- rich remnants of both intestinal chylomicrons and hepatic VLDL. Diagnosis of type III hyperlipoproteinemia is indicated by elevated plasma cholesterol and triglyceride, xanthomas (fatty eruptions under the skin), and of course the presence of -VLDL. Type I hyperlipoproteinemia (choice A) results from defects in the activity or activation of LPL and results in the massive accumulation of chylomicrons in the plasma. The disease is usually detected in childhood following recurrent attacks of abdominal pain, hepatosplenomegaly, and pancreatitis.
Familial hypercholesterolemia (choice B) is the result of defects in the LDL receptor. The defects lead to characteristic elevation in LDL, deposition of LDL-derived cholesterol in the tendons and skin and in the arteries. Individuals homozygous for defective LDL receptors have severe hypercholesterolemia (6501000 mg/dL) and coronary heart disease begins early in childhood with death caused by myocardial infarct before the age of 20. Type IV hyperlipoproteinemia (choice D) is associated with overproduction VLDLs. An associated glucose intolerance and hyperinsulinemia are also seen in this disorder. Wolman disease (choice E) is caused by a deficiency in lysosomal acid lipase and results in massive accumulation of cholesteryl esters and triglycerides in most tissues. The disease is almost always fatal before the age of 1 year.



I-cell disease (also identified as mucolipidosis type II) is characterized by the presence of inclusion bodies in fibroblasts (hence the derivation of the term I-cell), severe psychomotor retardation, corneal clouding, and dystosis multiplex. These symptoms arise from a defect in the targeting of lysosomal enzymes due to an inability to carry out which of the following processes?

  1. produce mannose-6-phosphate modifications in lysosomal enzymes
  2. recycle the lysosomal receptor for mannose-6-phosphate present on lysosomal enzymes
  3. remove mannose-6-phosphates from lysosomal enzymes prior to their transport to the lysosomes
  4. synthesize the mannose-6-phosphate receptor found in lysosomes
  5. transport mannose-6-phosphate receptors to lysosomes

Answer(s): A

Explanation:

Enzymes that are destined for the lysosomes (lysosomal enzymes) are directed there by a specific carbohydrate modification. During transit through the Golgi apparatus a residue of Nacetylglucosamine- 1- phosphate is added to carbon 6 of one or more specific mannose residues that have been incorporated into these enzymes. The N-acetylglucosamine is activated by coupling to UDP and is transferred by an Nacetylglucosamine phosphotransferase yielding N-acetylglucosamine-1- phosphate-6-mannoseprotein. A second reaction removes the Nacetylglucosamine leaving mannose residues phosphorylated in the sixth position. Aspecific mannose-6-phosphate receptor is present in the membranes of the Golgi apparatus.
Binding of mannose-6-phosphate to this receptor targets proteins to the lysosomes. Defects in the proper targeting of glycoproteins to the lysosomes can also lead to clinical complications. Deficiencies in N- acetylglucosamine phosphotransferase lead to the formation of dense inclusion bodies in fibroblasts. Two disorders related to deficiencies in the targeting of lysosomal enzymes are termed I-cell disease (mucolipidosis II) and pseudo-Hurler polydystrophy (mucolipidosis III). I-cell disease is characterized by severe psychomotor retardation, skeletal abnormalities, coarse facial features, painful restricted joint movement, and early mortality. Pseudo- Hurler polydystrophy is less severe; it progresses more slowly, and afflicted individuals live to adulthood. Each of the other choices (B, C, D, and E) represent other potential pathways that are not affected in the processing, delivery, or presentation of lysosomal enzymes or the receptors that recognize the properly processed enzymes.



A30-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?

  1. Hunter syndrome
  2. Hurler syndrome
  3. Maroteaux-Lamy syndrome
  4. Morquio syndrome type B
  5. Sanfilippo disease type A

Answer(s): B

Explanation:

Although multiorgan involvement, liver and spleen enlargement, and skeletal abnormalities are common to all the mucopolysaccharidotic (MPS) diseases, each encompasses features that allow for specific diagnosis. Hurler syndrome is characterized by progressive multiorgan failure and premature death.
Hallmark features include enlargement of the spleen and liver, severe skeletal deformity, and coarse facial features (which are associated with the constellation of defects referred to as dystosis multiplex). The disease results from a defect in alpha-L-iduronidase activity, which leads to intracellular accumulations of heparin sulfates and dermatan sulfates. The accumulation of these GAGs (glycosaminoglycan) in Hurler syndrome patients severely affect development of the skeletal system leading, primarily, to defective long bone growth plate disruption. Hunter syndrome (choice A) hasfeatures similar to that of Hurler with a lack of corneal clouding. Additionally, symptoms progress slower, with onset of symptoms occurring between 2 and 4 years of age. Maroteaux-Lamy syndrome (choice C) encompasses symptoms similar to Hurler but with normal mental development. Morquio syndrome (choice D) comprises two related disorders, both of which are characterized by short-trunk dwarfism, fine corneal deposits, and a skeletal dysplasia (spondyloepiphyseal) distinct from other MPS. Sanfilippo syndrome (choice E) comprises four recognized types characterized by severe CNS degeneration with only mild involvement of other organ systems.
Symptoms do not appear until 26 years of age.






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