A 4-year-old boy is brought to the paediatrician because of gastroenteritis for 3 days, followed by a brief generalized seizure that left him semicomatose. The blood glucose level at admission is 18 mg/dL (0.10 mM) and urine is negative for glucose and ketones, but positive for a variety of organic dicarboxylic acids. Intravenous administration of glucose improves his condition within 10 minutes. Following diagnosis of an enzyme deficiency, his parents are cautioned to make sure he rats frequently. Which of the following is the most likely diagnosis?

A 27-year-old medical student is unable to eat lunch and dinner during her clinical rotation. Which of the following enzymes is responsible for helping to maintain blood glucose levels by releasing glucose from its storage form in the liver?

A 2-year-old boy has a past medical history significant for mental retardation, hepatosplenomegaly, foam cells in the bone marrow, and neurologic deficits. The boy dies by the age of 3. Which of the following enzymes was most likely deficient in this child?

A 17-year-old high-school student comes to the school health clinic. She has missed her last menstrual period and is worried about being pregnant. In the past history, it is noted that she has sickle cell trait and mild asthma but is otherwise healthy. She has never been pregnant before and is sexually active with one boyfriend. They use barrier contraception on an irregular basis. She reports that her boyfriend once told her that he too had sickle cell trait. She is determined to continue with the pregnancy if the urine pregnancy test turns out to be positive. Her main concern is whether her child will have sickle cell anemia. At this stage, it is appropriate to counsel her that in cases where both parents have sickle cell trait the risk of having a baby born with sickle cell anemia is which of the following?

A 36-year old Greek man with viral pneumonia has a self-limiting episode of hemolysis. Over the next week, he as an increased rate of reticulocytosis. Which of the following serves as a precursor in a pathway that allows the newly matured erythrocytes to participate in oxygen transport ?

Pseudogenes are homologues of functional genes that lack promoters and are therefore part of the unexpressed DNA. It is thought that at least some of these pseudogenes were produced by reverse transcription of mRNA and insertion of the resultant cDNA into a chromosome by a virus. In addition to lacking a promoter and other regulatory elements, a pseudogene produced in this manner will also differ from the authentic gene in which one of the following ways ?

A 69-year-old edentulous alcoholic man, who lives alone, is admitted to the hospital for evaluation of a shoulder wound that is not healing well. On physical examination, numerous ecchymoses are noted on the posterior aspect of his legs and thighs. Careful examination of the man’s skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds. Laboratory examination is remarkable for a hemoglobin of 10 g/dL; no other hematologic abnormalities are noted. Which of the following is the most appropriate therapy for this disorder?

A 28 year old woman and a 25 year old man present for generic counselling. Both are white and have one sibling affected with cystic fibrosis. Which of the following is the most appropriate method for assessing the risk of cystic fibrosis transmission to the child ?

A lethal mutation occurs in a bacterium, rendering it incapable of replicating its chromosome. Because of this mutation, DNA synthesis produces many short fragments of DNA that have RNA sequences at their 5′ ends. The mutation is most likely in a gene encoding which of the following?

Liver cells in culture were kept at 0o C (32.0oF) and treated with trypsin to digest the receptors on the cell surface. The temperature was then raised to 37.0oC (98.6oF), and radioactive LDL was added to the culture media. Several hours later, the labeled LDL was found to be inside the cells. Which of the following represents the process of LDL uptake by hepatocytes?

A 23-year-old, single, unemployed woman in her eighth month of pregnancy is seen in a volunteer-staffed obstetrics clinic. Her first child, born at home and exclusively breast-fed, had prolonged diarrhea and died from an intracranial hemorrhage at 1 month of age. To help prevent a similar problem in this pregnancy, the resident gives her a free prescription for a vitamin and advises her to take one 20-mg tablet each day. He also informs her that the infant should receive an injection of this vitamin soon after birth. The vitamin prescribed is required as a coenzyme by which of the following enzymes?

A newborn vomits after each feeding of milk-based formula and does not gain weight. Biochemical testing reveals a severe deficiency of galactose- 1 -phosphate uridyltransferase, consistent with homozygosity. If this condition goes untreated, which of the following is the likely outcome for this patient?

A 45-year-old man is diagnosed with cancer of the proximal portion of the colon. His father died of colon cancer at the age of 52. He has three siblings. His 55-year-old brother has not been diagnosed with cancer, but his 57-year-old sister has an endometrial carcinoma, and his other sister died of ovarian cancer. A diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) is made. Which of the following types of mutations most likely occurred in this family?

A 5 year old mentally retarded boy is brought to the city from a rural community for evaluation. A careful history reveals mental retardation in a number of other family members, especially the males. Physical examination is remarkable for a long face with large ears, a large jaw, and bilateral enlargement of the testes. This presentation is suggestive of

A 22-year-old woman presents with a fusiform swelling of the Achilles tendon, which, when biopsied, shows cholesterol-laden macrophages (foam cells) dispersed among the collagen fibers. She had been troubled with joint pains for several years. Both her mother and father developed arthritis associated with production of xanthomas, but their first symptoms occurred in middle age. She was referred to a nutritionist and treated with an enzyme inhibitor. Which of the following is most likely elevated in the blood of this woman?

A 62 year old man is prescribed a pharmaceutical agent that inhibits the activity of the enzymes HMF-CoA reducatase. This patient most likely has which of the following conditions ?

Several members of a family have an autosomal recessive disease characterized by intellectual deterioration, weakness, ataxia, seizures, and death at a young age. Special studies demonstrate a deficiency of cytochmme C oxidase activity. Which of the following subcellular organelles is defective in affected members of this family?

A 12-year-old boy has a particular genetic disease. His mother is a carrier of the mutated gene, but his father is not clinically affected and is not a carrier. The man has four siblings: a sister and 2 brother who are not clinically affected and are not carriers; a sister who is a carrier but is not clinically affected-and a brother who is clinically affected. This inheritance pattern is consistent with which of the following diseases?

A previously normal child begins deteriorating developmentally at about 6 months of age. She is seen by an ophthalmologist because she no longer responds to visual stimuli. A cherry-red spot on the macula is noted on ophthalmologic examination. The enzyme that is deficient in this child normally carries out which of the following functions?

A 4-year-old retarded child hurls himself into walls and bites his fingertips so severely that they must be heavily bandaged. This child most likely has a deficiency of which of the following enzymes?

A patient with acute lymphocytic leukemia is treated appropriately with antineoplastic therapy. Inhibition of which of the following enzymes will help prevent side effects of this therapy?

Methotrexate is used as therapy for rheumatoid arthritis, but has many side effects related to competitive inhibition of the enzyme dihydrofolate reductase. These side effects can be decreased without interfering with the efficacy of methotrexate by ingestion of additional folate. If patients treated with methotrexate are given sufficient folate, which of the following would most likely occur?

A college student goes to a fraternity party and consumes large quantities of beer. The alcohol in the beer is metabolized by the liver, with almost half the alcohol being oxidized to acetaldehyde. In which of the following sites does this reaction occur?

The pregnant mother of a 6-year-old son with glucose¬6-phosphate dehydrogenase deficiency is very worried that her female fetus will have the disease. The father and mother are clinically normal. Which of the following is true about her baby?

A 24-year-old woman with phenylketonuria (PKU) gives birth to her first child. Although there is no history of PKU in the father’s family, the couple could not afford genetic testing of the father or consistent prenatal care. At birth, the child is small, microcephalic, and has elevated blood phenylalanine. What is the most likely explanation for this neonate’s symptoms?

A rapid way to purify proteins that are targeted to lysosomes would be to use affinity chromatography. An appropriate antibody to use on an affinity chromatography column would be one directed against:

A 5-year-old boy has temporary weakness and cramping of skeletal muscle after exercise. He has normal mental development. This child most likely has a deficiency of which of the following enzymes?

Following the ingestion of glyburide, a type 2 diabetic patient begins to experience anxiety, diaphoresis, and hunger. The patient subsequently ingests a health food bar containing glucose. Which of the following is required to initiate the process of energy production from the ingested glucose?

A 30-year-old vegetarian presents to his physician complaining of diminished sensation in his lower extremities. He has not eaten meat for the past 15 years. A complete blood count reveals hypersegmented neutrophils and elevated mean corpuscular volume. Which of the following findings would be expected on urinalysis?

A 50-year-old chronic alcoholic presents with dementia, paralysis of lateral gaze, and difficulty walking. The vitamin deficient in this patient is required as a cofactor for which of the following enzymes?

A 30-year-old man has been fasting for religious reasons for several days. His blood glucose level is now about 60% of its normal value, but he does not feel lightheaded because his brain has reduced its need for serum glucose by using which of the following substances as an alternate energy source?

When a cloned DNA fragment is used as a probe, a restriction fragment length polymorphism (RFLP) is revealed in the region adjacent to the centromere of chromosome 21. Four haplotypes exist: A, B. C, and D. An AB woman and a CD man have an ACC child with trisomy 21. Nondisjunction most likely occurred during which of the following?

A 7 year old is brought to the emergency department by her parents with a complaint of severe polyuria and polydipsia. Laboratory examination reveals ketones in her urine. Which of the following is the most likely source of the ketones ?

A 58 year old woman is admitted to the hospital with fever, abdominal cramps, and severe watery diarrhea. The symptoms began one day after attending a banquet. She was treated with ciprofloxacin, but her condition did not improve. PCR amplification and analysis of a gene region in the bacteria isolated from the patient revealed a missense mutation that conferred resistance to ciprofloxacin. The missense mutation is most likely in the gene encoding an enzyme essential for which of the following functions ?

A 2-year-old boy is diagnosed with a biochemical defect involving hexosaminiclase A. The patient’s condition would be most appropriately categorized as belonging to which of the following general classes of defects?

A 26-year-old pregnant woman complains of persistent, dry, ulcerated skin over her knees and elbows. Examination of her eyes reveals small, gray plaques on the conjunctiva. Which of the following is the most likely diagnosis?

On physical examination, a newborn is found to have micrognathia, a prominent occiput, low-set ears, and rocker-bottom feet. There is very little mental development during the first months of life, and the infant dies of cardiac complications after 8 months. A complete karyotype of this child would show which of the following?

A patient with short stature presents with hypoglycemia, hepatomegaly, bleeding diathesis, hepatic adenomas, and enlarged kidneys. Laboratory evaluation reveals the presence of increased lactate, cholesterol, triglyceride, and uric acid. This patient most likely has a deficiency of which of the following enzymes?

A gene product thought to be involved in the down-regulation of fetal hemoglobin expression is being investigated. Samples of primary tissue cultures of fetal, neonatal, and adult liver and bone marrow, as well as adequate amounts of a DNA probe believed to contain the studied gene, are provided. Which of the following techniques is the best for determining the tissue culture sample that is expressing the gene of interest?

A researcher is trying to identify a specific protein within a mixture. He subjects the mixture to gel electrophoresis and then transfers the separation to nitrocellulose filters. The filters are incubated with antibody to the specific protein, and the excess antibody is washed off. The antibody-protein complex is then incubated with a radiolabelled protein that hinds to the antibody. Autoradiography is performed to detect the presence of the protein. Which of the following is the technique being carried out by the researcher?

A neonate with ambiguous genitalia and microcephaly is suspected of having a genetic disease characterized by failure to metabolize 7-dehydrocholesterol to cholesterol. Which of the following is the most likely diagnosis?

A newborn presents with severe acidosis, vomiting, hypotonia, and neurologic deficits. Laboratory analysis reveals elevated levels of lactate and alanine. These observations suggest a deficiency of which of the following enzymes?

A prokaryotic operon codes for two enzymes and one regulatory protein. The operon is expressed only in the presence of a particular sugar. Initial mapping of the operon has differentiated the nontranscribed sequences from the transcribed sequences. Deletion of 10 nucleotides from one of the nontranscribed sequences results in transcription of the operon in both the presence and absence of the sugar. Which of the following sequences was most likely affected?

A genetics researcher is trying to identify a potential gene from a gene signature/motif that encodes a seven-helix transmembrane domain. Which of the following is most likely the protein encoded by the researchers’ target gene?