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Free STEP1 Exam Braindumps (page: 69)

Page 68 of 213
PDF with 845 Questions

A6-month-old who is failing to thrive is brought to your clinic. Tests reveal hepatosplenomegaly, muscle weakness and atrophy, hypotonia, and decreased deep tendon reflexes. Blood tests reveal that the infant has normal glucose levels. Biopsy of the liver reveals initial stages of cirrhosis due to the accumulation of an abnormal glycogen with few branch points, whose structure resembles amylopectin. The clinical and laboratory results presented are indicative of which glycogen storage disease?

  1. Andersen disease (type IV glycogen storage disease)
  2. Cori or Forbes disease (type III glycogen storage disease)
  3. McArdle disease (type V glycogen storage disease)
  4. Tarui disease (type VII glycogen storage disease)
  5. von Gierke disease (type I glycogen storage disease)

Answer(s): A

Explanation:

Andersen disease (also referred to as type IV glycogen storage disease) manifests its symptoms as a result of the accumulation of glycogen, with unbranched long outer chains in tissues. This structure of glycogen resembles that of plant amylopectin. Symptoms appear within the first year of life and lead to failure to thrive and pronounced heptosplenomegaly. Hypoglyemia is rarely seen with this disorder. Cori disease (choice B) affects both liver and muscle with accumulations of glycogen that has short outer chains (resembles limit dextrin). Symptoms include hepatomegaly, hypoglycemia, hyperlipidemia, and retarded growth. McArdle disease (choice C) usually manifests in adulthood and characteristic symptoms include exercise intolerance, muscle cramping with exercise, and myoglobinuria. The affected tissue in this disease is only skeletal muscle. Tarui disease (choice D) also affects skeletal muscle and as such manifests with clinical symptoms very similar to those of McArdle disease with the exceptions that Tarui patients also experience hemolytic anemia and myogenic hyperuricemia. Symptoms of von Gierke disease (choice E) result from the excessive accumulation of glycogen in liver, kidney, and intestinal mucosa.
Symptoms include growth retardation, hypoglycemia, heptomegaly, hyperlipidemia, lactic acidemia, and hyperuricemia.



Analysis of a tumor cell line indicates that there is a dramatically increased level in the activity of the transcription factor E2F. Which of the following is the most likely explanation for this observation?

  1. an increase in the expression of pRB resulting in increased binding of pRB to E2F
  2. hypophosphorylation of pRB so that it can no longer interact with E2F
  3. loss of expression of pRB which normally activates E2F
  4. mutation in pRB that prevents its phosphorylation so that it cannot interact with the gene to which it normally binds and coactivates with E2F
  5. mutation in the domain of pRB to which E2F binds, the consequences of which lead to constitutive E2F activity

Answer(s): E

Explanation:

Members of the E2F family of transcription factors play critical roles in regulating cell-cycle transit through the G1-S restriction point. The activity of E2F is regulated by interaction with the protein product of the retinoblastoma susceptibility tumor suppressor gene, pRB. Interaction of pRB and E2F occurs when pRB is in a hypophosphorylated state (below figure).

Members of the cyclin-dependent kinase family of cell-cycle regulating kinases target pRB for phosphorylation. When phosphorylated, pRB dissociates from E2F allowing E2F to enter the nucleus and transcriptionally activate genes involved in DNA synthesis, as well as activate its own transcription.
Transcription of both cyclin E and CDK2 are activated by E2F. These two proteins form a complex that promotes progression through S-phase of the cell cycle and also act to keep E2F active by adding to the phosphorylation state of pRB (below figure). Thus, any defect in the ability of pRB to bind to E2F will lead to constitutive activation of DNA synthesis leading to unrestrained proliferation. None of the other options (choices AD) represent viable phenomena to account for the observed increase in E2F activity.



Chromatin remodeling is associated with alterations in the transcriptional activity of genes in the region of the remodeling. Which of the following statements is most correct concerning the events of chromatin remodeling?

  1. Chromatin remodeling occurs predominantly in regions enriched in CpG dinucleotides.
  2. Histone acetylation tends to destabilize chromatin structure.
  3. Methylation of cytosine residues induces the remodeling event.
  4. Methylation of histone H1 is sufficient to stimulate remodeling.
  5. Remodeling is necessary to induce the property of genomic imprinting.

Answer(s): B

Explanation:

The posttranslational modification of histone proteins has considerable effect on numerous activities at the level of the chromatin. In particular, the acetylation and/or methylation of histones in the nucleosome (H2A, H2B, H3, and H4) results in an altered stability of the 30-nm chromatin fiber as well as other higher order chromatin structure. No specific regions of remodeling have been identified relative to sequence content such as CpG islands (choice A). Methylation of cytosine residues in the DNA (choice C) has an effect on transcriptional activity but not on chromatin structure. Methylation of the linker histone, H1 (choice D) has not been demonstrated. Chromtin remodeling does not direct imprinting (choice E). Imprinting is regulated by the state of DNA methylation.



A 4-month-old Caucasian male infant with a temperature of 38.4°C is examined by his pediatrician. His mother indicates that he has had the fever for the past 4 days, been listless, vomiting, and has watery stools. Blood work indicates the infant is hypoglycemic but this condition does not respond to either epinephrine or glucose administration. In addition, his blood pH is slightly acidic and shows reduced bicarbonate. Other untoward blood chemistry includes elevated triglycerides, cholesterol, and liver enzymes. The child has a protruberant abdomen, thin extremities, and a doll-like face. The pediatrician suspects a specific condition and orders a liver biopsy to test for the activity of which of the following enzyme activities?

  1. glucose-6-phosphatase
  2. glycogen synthase
  3. muscle phosphofructokinase
  4. muscle phosphorylase
  5. pyruvate kinase

Answer(s): A

Explanation:

Deficiency in glucose-6-phosphatase (choice A) is one cause of glycogen storage disease type I (specifically type Ia, von Gierke disease). Hallmarks of the disease are hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. If symptoms do not appear until the third or fourth month they include hepatomegaly and hypoglycemic seizures. Afflicted children have a protruberant abdomen due to the massive hepatomegaly. Outward physical signs also include extremely thin extremities, short stature, and chubby doll-like faces. Liver glycogen synthase deficiency (choice B) presents with morning fatigue and ketotic hypoglycemia on fasting--both of which rapidly disappear on feeding. Symptoms can be rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and nighttime feedings of suspensions of uncooked corn starch. Adeficiency in muscle phosphofructokinase (choice C) results in glycogen storage disease type VII (Tarui disease). Clinically, the symptoms seen in Tarui disease are very similar to those seen in muscle phosphorylase deficiency (choice D), glycogen storage disease type V (McArdle disease) such as exercise-induced cramping and early fatigue. There are five clinical characteristics allowing distinction betweeen Tarui and McArdle disease: exercise intolerance is evident in childhood and more severe and is associated with nausea and vomiting; the intolerance is particularly acute following meals rich in carbohydrates; hyperuricemia is more severe; compensated hemolytic anemia is evidenced by increased serum bilirubin and reticulocyte count, and lastly; an abnormal polysaccharide is present in muscle fibers. Deficiency in PK (choice E) is the most common enzyme deficiency leading to hemolytic anemia and the disorder is characterized by lifelong episodes. The most severe deficiency will result in embryonic lethality.






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