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Genetic Medicine: Clinical Genetics and Inborn Errors of Metabolism - Part 1 (20 test)
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1. Parents bring in a 2-week-old Caucasian male infant fearful that he has ingested a poison. They had delayed disposing one of the child’s diapers, and noted a black discoloration where the urine had Later, they realized that all of the child’s diapers would turn black if stored as waste for a day or so. Knowing that phenol groups can complex to form colors, which of the following amino acid pathways are implicated in this phenomenon?
- The phenylalanine, tyrosine, and homogentisate pathway
- The histidine pathway
- The leucine, isoleucine, and valine pathway
- The methionine and homocystine pathway
- The arginine and citrulline pathway (urea cycle)
2. Inherited deficiency of the enzyme methylmalonyl-CoA mutase (MMACoA mutase, MIM*251000) causes serum and urine accumulation of methylmalonic acid with acidosis, neurologic degeneration, and death. Recognition that pernicious anemia (due to deficiency of vitamin B12) can involve accumulation of methylmalonic acid led to successful treatment of some patients with MMACoA mutase deficiency using excess B12. Studies of purified MMACoA mutase enzyme from normal patients then showed enhanced mutase activity when B12 was added to the reaction These facts are best reconciled by which of the following explanations?
- Vitamin B12 is a precursor for methylmalonic acid
- Vitamin B12 is a prosthetic group for the enzyme MMACoA
- Vitamin B12 is a cofactor for the MMACoA mutase
- Vitamin B12 is a competitive inhibitor of MMACoA mutase
- Vitamin B12 is a feedback inhibitor of MMACoA mutase
3. A 13-year-old African American adolescent is brought in by his parents after his physical education teacher gives him a failing The teacher has scolded him for malingering because he drops out of activities after a few minutes of exercise, complaining of leg cramps and fatigue. A stress test is arranged with sampling of blood metabolites and monitoring of exercise performance. Which of the following results after exercise would support a diagnosis of glycogen storage disease in this teenager?
- Increased oxaloacetate, decreased glucose
- Increased glycerol and glucose
- Increased lactate and glucose
- Increased pyruvate and stable glucose
- Stable lactate and glucose
4. A 2-year-old Caucasian girl has ingested cyanide from her parents’ garage and is rushed to the emergency Which of the following components of the citric acid cycle will be depleted first in this child?
- NAD+ cofactor
- Citrate synthase
- Citrate production
- Acetyl-CoA production
5. A 45-year-old insurance executive is found comatose in his garage with the car engine running and transported by ambulance to the emergency He has the typical coal gas breath and red flush to the face and lips with blue (cyanotic) nail beds. Which of the following options indicates the steps of the respiratory chain (as diagramed below) that will be in a reduced state in this patient?
- Steps A and B
- Steps A, B, and C
- Step D alone
- Step E alone
- All steps (A-E)
6. A 2-day-old Caucasian boy becomes progressively lethargic after feeding and increases his respiratory rate. He becomes virtually comatose, responding only to painful stimuli, and exhibits mild respiratory alkalosis. Suspicion of a urea cycle disorder is aroused, and evaluation of serum amino acid levels is In the presence of hyperammonemia, production of which of the following amino acids is always increased?
7. A 2-year-old African American girl has been healthy until the past weekend when she contracted a viral illness at day care with vomiting, diarrhea, and progressive lethargy. She presents to the office on Monday having been unable to eat and drink much over the weekend; she is lethargic with signs of dehydration including cracked lips, sunken eyes, lack of tears, and flaccid skin with “tenting” on pinching. She also has a weak pulse with low blood pressure and increased deep tendon Laboratory tests show low blood glucose, normal electrolytes, elevated liver enzymes, and (on chest x-ray) a dilated heart. Urinalysis reveals no infection and no ketones. The child is hospitalized and stabilized with 10% glucose infusion, and certain admission laboratories come back 1 week later showing elevated medium-chain fatty acyl carnitines in blood and six to eight carbon dicarboxylic acids in the urine. The most likely disorder in this child involves which of the following?
- Defect of medium-chain coenzyme A dehydrogenase
- Defect of medium-chain fatty acyl synthetase
- Mitochondrial defect in the electron transport chain
- Glycogen storage disease
- Urea cycle disorder
8. A 15-year-old Caucasian adolescent has a long history of school problems and is labeled as His tissues are puffy, giving his face a “coarse” appearance. His IQ tests have declined recently and are now markedly below normal. Laboratory studies demonstrate normal amounts of sphingolipids in fibroblast cultures with increased amounts of glycosaminoglycans in urine. Which of the following enzyme deficiencies might explain the intellectual deterioration?
- Hexosaminidase A
9. A 3-month-old African American boy presents with poor feeding and growth, low muscle tone (hypotonia), elevation of blood lactic acid (lactic acidemia), and mild acidosis (blood pH 3-7.35). The ratio of pyruvate to lactate in serum is elevated, and there is decreased conversion of pyruvate to acetyl coenzyme A in fibroblasts. Which of the following compounds should be considered for therapy?
- Free fatty acids
- Ascorbic acid
10. Which of the following characteristics is most typical of multifactorial inheritance?
- Sex predilection
- Mitochondrial inheritance
- Recurrence risks reflect the number of affected relatives
- Major cause of miscarriages
- Maternally derived
11. A physician evaluates a 16-year-old Caucasian adolescent with a slightly unusual facial appearance and poor school performance. A peripheral blood chromosome study reveals a karyotype of 46,XY/47,XY,+8 mosaicism, with 10% of 100 examined cells showing the extra chromosome 8. Which of the following options is most appropriate for the physician during the counseling session that follows the chromosome result?
- Recommend karyotyping of the parents.
- Explain that the recurrence risk for such chromosomal aberrations is about 1%.
- Urge that the school receives a copy of the karyotype, since these boys often have behavior problems.
- Recommend special education.
- Inform the parents that their child will be sterile.
12. A 4-year-old Caucasian boy presents to the physician’s office with coarse facies, short stature, stiffening of the joints, and mental retardation. The physician performs a urine screen that shows elevated mucopolysaccharides and makes a tentative diagnosis of mucopolysaccharidosis. The boy’s parents, a 10-year-old sister, and an 8-year-old brother all appear unaffected but the mother had a brother who died at 15 years of age with similar findings that seemed to worsen with The mother also has a nephew (her sister’s son) who exhibits similar clinical findings. During the evaluation of her son, the mother reveals she is 5 months pregnant. Based on the probable mode of inheritance, which of the following is the risk that her fetus is affected?
- Virtually 0%
13. A couple comes to the physician’s office after having had two sons affected with a similar The first-born son is tall and thin and has dislocated lenses and an IQ of 70. He has also experienced several episodes of deep vein thromboses. The chart mentions deficiency of the enzyme cystathionine-β-synthase, but a diagnosis is not given. The second son was treated from an early age with pyridoxine (vitamin B6) and is less severely affected. No other family members are affected. While taking a family history, the physician discovers that the parents are first cousins. The 38-year-old mother is pregnant, and amniocentesis has demonstrated that the fetus has a 46,XY karyotype. What is the risk that the fetus will be affected with the same disease?
- Virtually 0%
14. A 35-year-old African American male affected with Crouzon syndrome (MIM*123500) has craniosynostosis (ie, premature closure of the skull sutures) along with unusual facies that includes proptosis secondary to shallow orbits, hypoplasia of the maxilla, and a prominent nose. His son and brother are also affected, although two daughters and his wife are The patient and his wife are considering having another child. Their physician counsels them that their child might inherit Crouzon syndrome from his father. Which of the following risk percentages are most likely?
- Virtually 0%
15. Waardenburg syndrome (MIM*193500) is an autosomal dominant condition that accounts for 1.4% of cases of congenital In addition to deafness, patients with this condition have an atypical facial appearance, including lateral displacement of the inner canthi (eye corners), hypertelorism (widely spaced eyes), poliosis (white forelock), and white patches of skin on the ventral midline (partial albinism or piebaldism). A mother has Waardenburg syndrome, her husband is unaffected, and they plan to have a family with three children. What is the probability that only one of the three children will be affected?
- c. 3/8
- d. 1/3
16. Phenylketonuria (PKU—MIM*261600) is an autosomal recessive disease that causes severe mental retardation if it is Two normal parents are told by their state neonatal screening program that their third child has PKU. Assuming that the initial screening is accurate, what is the risk that their first child is a carrier for PKU?
- Virtually 0%
17. Individuals with Parkinson disease (PD-MIM*168601) have dopamine deficiency in the substantia nigra of the central nervous Which of the following would comprise the best strategy for therapy?
- Feedback inhibition of dopamine oxidation
- Competitive inhibition of biosynthesis from histidine
- Provision of metabolites in the tyrosine pathway
- Stimulation of monoamine oxidase
- Provision of metabolites in the alanine pathway
18. A 3-year-old Caucasian girl is scheduled for a tonsillectomy. As she is prepared for the operating room, her father becomes agitated and insists on accompanying her. He says that he lost a son several years ago when the child did not wake up after an Which of the following options is the best response to the father’s anxiety?
- Postpone the operation until the psychiatric state of the father can be evaluated
- Proceed after explaining that problems in a previous child are unlikely to be present in his daughter
- Proceed after reassuring the father that drug reactions are environmental and unlikely to have a genetic basis
- Postpone the operation until a more detailed family history is obtained
- Proceed after explaining that modern anesthetic procedures are much safer than in the past
19. A couple request prenatal diagnosis because a maternal uncle and a male cousin on the wife’s side were diagnosed with Lesch-Nyhan syndrome (MIM*308000). DNA analysis of the family is performed using Southern blotting with VNTR probes near the HGPRT gene, shown below. What is the chance that the fetus will have Lesch-Nyhan syndrome?
- Virtually 0%
20. A 6-year-old girl is referred to a physician for evaluation. She is known to have mild mental retardation and a ventricular septal defect (VSD). On physical examination, the patient is noted to have some facial dysmorphism, including a long face, a prominent nose, and flattening in the malar In addition, the patient’s speech has an unusual quality. Which of the following descriptions best explains the patient’s condition?
- Single birth defect