An 18-month-old boy is brought to the office due to language regression.  He said several words at his 1-year appointment but now no longer speaks any words at all.  His moods have also become more unpredictable over the past 4 months with frequent tantrums.  The parents tried to bring him in sooner for evaluation, but they live in an impoverished part of the city and experienced financial difficulties with transportation to the office.  On physical examination, the boy is quiet and maintains appropriate eye contact throughout the visit.  Hemoglobin is 9 g/dL.  Which of the following enzymes is most likely inhibited in this patient?

A 22-year-old woman comes to the hospital due to a 5-day history of nausea, constipation, and severe, poorly localized abdominal pain.  She also reports anxiety, difficulty concentrating, poor sleep quality, and tingling of the limbs.  The patient has had several similar episodes in the past.  She does not take any medications or use tobacco, alcohol, or illicit drugs.  The patient has been restricting her diet to lose weight.  On examination, the abdomen is soft, nontender, and nondistended.  Bowel sounds are decreased.  The patient receives an intravenous infusion of a heme preparation that leads to rapid resolution of her symptoms.  The improvement in symptoms is most likely due to treatment-induced downregulation of which of the following enzymes?

A 17-year-old girl comes to the office for follow-up on anemia.  She has taken iron supplements regularly since being diagnosed with iron deficiency anemia 3 months ago.  However, the patient still feels fatigued and does not think that the supplements have improved her symptoms.  She has occasional gingival bleeding when brushing her teeth.  Menses occur every 27-28 days and last 7-8 days with heavy flow, sometimes requiring her to change pads every hour.  Platelet count is normal.  Further evaluation reveals that the patient’s platelets do not agglutinate appropriately in response to ristocetin.  When normal plasma is added to the solution of patient platelets and ristocetin, appropriate platelet agglutination occurs.  Which of the following is most likely deficient in this patient?

A 7-year-old African American boy is brought to the office by his parents.  The parents state that the boy has been hospitalized several times for severe pains in his back and extremities.  The patient is very active when he is not in pain but gets quite tired by the end of the day.  He has no other medical problems and takes no medications except acetaminophen for pain control.  On examination, the conjunctivae are pale.  Blood count reveals a hemoglobin level of 7.8 mg/dL and a reticulocyte count of 15%.  A valine for glutamic acid substitution at position 6 of the β globin chain of the hemoglobin molecule is suspected.  This patient’s hemoglobin would most likely aggregate upon which of the following?

A 40-year-old woman comes to the office with a 3-month history of progressively limited physical activity due to fatigue.  The patient says, “I could barely walk from my car to the office.”  Medical history is significant for a positive tuberculin skin test 7 months ago with a normal chest radiograph.  She has been compliant with the prescribed treatment despite its bitter taste.  Physical examination shows a tired-appearing woman with conjunctival and palmar pallor.  Complete blood count is as follows:

A bone marrow aspirate representative of this patient’s disease process is shown below (Prussian blue stain).

Decreased activity of which of the following enzymes most likely explains the anemia found in this patient?

A 2-day-old boy is being examined in the newborn nursery prior to discharge from the hospital.  He was born at 38 weeks gestation by vaginal delivery.  The pregnancy and delivery were uncomplicated, and the boy has been breastfeeding, stooling, and urinating normally.  The patient’s mother has beta-thalassemia trait, and his father has a normal hemoglobin electrophoresis.  Vital signs and physical examination are normal.  Which of the following hemoglobin compositions is most likely predominant in this infant?

An infant born to a Greek immigrant appears healthy at birth but develops transfusion-dependent hemolytic anemia by the age of 6 months.  His erythrocytes contain insoluble aggregates of hemoglobin subunits.  The child developed normally in utero because at that time he produced high quantities of:

Hemoglobin C (HbC) disease is due to a single amino acid substitution (glutamic acid → lysine) at position 6 in the beta globin chain of the hemoglobin molecule.  Hemoglobin S (HbS) is similar to HbC in that it is also formed by an amino acid substitution at position 6 in the beta globin chain.  However, patients homozygous for HbC have mild chronic hemolytic anemia, whereas those homozygous for HbS generally have a more severe anemia complicated by vasoocclusive pain episodes.  Which of the following properties best accounts for the differing clinical severity between the two conditions?

A 6-year-old African American boy is brought to the physician because of easy fatigability.  Physical examination reveals splenomegaly, and his complete blood count shows mild anemia.  Hemoglobin electrophoresis is performed at alkaline pH on a cellulose acetate strip.  Findings for the patient are shown below compared to individuals with normal hemoglobin and known sickle cell disease.

Which of the following is the most likely cause of this patient’s condition?

A 54-year-old man with a history of chronic kidney disease due to hypertension develops anemia.  Evaluation reveals that the cause of anemia is erythropoietin deficiency.  Erythropoietin increases the numbers of erythroid precursor cells in the bone marrow and induces heme production in erythrocyte precursors.  In this patient, mature erythrocytes are found that are unable to synthesize heme even though they contain detectable levels of cytoplasmic enzymes involved in heme synthesis.  Lack of which of the following cellular organelles best explains this phenomenon?

A 14-year-old boy with chronic anemia is being evaluated after experiencing several episodes of chest, back, and extremity pain.  Peripheral blood smear shows sickle-shaped red cells.  Genetic testing reveals that the patient is homozygous for a point mutation in the beta-globin gene, resulting in a glutamic acid to valine substitution at position 6.  Sequencing of the beta-globin gene would most likely reveal which of the following changes? (The genetic code is shown in the figure below.)

A 22-year-old man comes to the office due to recurrent blistering on the back of his hands and forearms for the past several years.  The patient usually develops small itchy spots but lately has had large blisters that heal with hyperpigmentation after rupturing.  He has used over-the-counter topical hydrocortisone and emollients, but the symptoms have not improved.  The patient works as a night security guard and has had no exposure to chemicals or animals.  He drinks 2-3 cans of beer daily.  Physical examination shows vesicles and erosions on the dorsum of both hands.  Which of the following enzymes is most likely deficient in this patient?

A 68-year-old woman comes to the office due to recurrent bacterial sinusitis, pneumonia, and urinary tract infections over the past several months.  The patient has no prior medical conditions or history of severe infections in childhood.  She does not use tobacco, alcohol, or illicit drugs.  Temperature is 36.6 C (97.9 F), blood pressure is 130/76 mm Hg, and pulse is 72/min.  On physical examination, the lungs are clear to auscultation, heart sounds are normal, and the abdomen is soft and nontender with no hepatosplenomegaly.  Laboratory testing reveals normocytic normochromic anemia.  Bone marrow aspirate shows an increased number of cells, as shown below.

Which of the following is the most likely cause of this patient’s increased susceptibility to infections?

A 12-year-old boy experiences excessive bleeding following a tooth extraction.  His past medical history includes episodes of painful joint swelling from minor trauma.  Physical examination shows a soft and nontender abdomen with a liver span of 10 cm.  The spleen is not palpable.  Laboratory results are as follows:

This patient most likely has a deficiency involving which of the following factors?

A 64-year-old man is brought to the emergency department due to severe chest pain, diaphoresis, and shortness of breath.  Symptoms began suddenly on awakening and have worsened over the past 2 hours.  Blood pressure is 150/90 mm Hg and pulse is 102/min.  Physical examination reveals an S4.  ECG shows ST-segment depression and T-wave inversion in the lateral leads.  Coronary angiography reveals a ruptured atherosclerotic plaque, with a thrombus in the left circumflex artery that causes near-total occlusion.  Normal endothelial cells surrounding the lesion have released large amounts of a chemical substance that help decrease thrombus propagation by inhibiting platelet aggregation.  Which of the following substances was most likely secreted by these endothelial cells?

A 63-year-old woman is hospitalized because of dyspnea on exertion and generalized fatigue.  She has been hospitalized 3 times during the past year for heart failure exacerbations.  Her other medical problems include essential hypertension for 20 years, myocardial infarction at the age of 58, and hypercholesterolemia.  She has a 36-pack-year smoking history in addition to a 10-year history of alcohol abuse.  Physical examination reveals tachycardia, distended neck veins, bilateral crackles on lung auscultation, a third heart sound on cardiac auscultation, and pedal edema.  The appropriate therapy is initiated.  On the third day of hospitalization, her hematocrit level increases to 50%, up from 44% on admission.  An arterial blood gas analysis shows an arterial O₂ partial pressure (PaO₂) of 70 mm Hg.  A ⁵¹Cr-tagged red blood cell infusion indicates normal red blood cell mass.  Which of the following is the most likely cause of this patient’s polycythemia?

A 3-year-old boy is brought to the office by his parents due to constipation.  The boy previously had soft stools 1-2 times daily.  However, over the past 3 months, his bowel movements have decreased to 1 stool every 3-4 days with significant straining and production of hard stool balls.  The boy has intermittent diffuse abdominal pain and increased irritability, but these symptoms have not affected his overall appetite.  Family history is notable for a maternal aunt with celiac disease and a paternal grandmother with “thyroid problems.”  Four months ago, the boy and his parents moved into a house owned by their family for generations, and the parents are worried that the stress of the move might be contributing to his symptoms.  Height and weight have been tracking appropriately.  Physical examination shows a pale, tired boy with palpable stool in his abdomen but no abdominal tenderness.  Which of the following is the most appropriate diagnostic test for this patient?

A 72-year-old woman is evaluated due to a month of fatigue and shortness of breath on exertion.  The patient has also had lower back pain but no fever or cough.  She takes valsartan for hypertension.  Temperature is 37.2 C (99 F), blood pressure is 130/80 mm Hg, pulse is 84/min, and respirations are 14/min.  On physical examination, the conjunctivae are pale.  The remainder of the examination is normal.  Laboratory results are as follows:

X-rays of the lower back demonstrate multiple areas of radiolucency in the L4 and L5 vertebrae.  Serum protein electrophoresis reveals a monoclonal gamma globulin spike.  Further studies are most likely to show which of the following?

A 64-year-old man comes to the office due to persistent back pain, constipation, and easy fatigability for the last several months.  Blood pressure is 115/75 mm Hg and pulse is 88/min.  The patient has dry mucous membranes.  Laboratory results are as follows:

Renal biopsy is performed and light microscopy shows atrophic tubules, many of which contain large, obstructing, waxy casts that stain intensely with eosin.  Which of the following is the most likely diagnosis in this patient?

A 4-year-old girl developed acute-onset colicky abdominal pain, vomiting, and loose bloody stools during a family vacation.  She was treated with supportive care and began to feel better.  A few days later, her parents bring her to the emergency department because she has urinated only once in the past 10 hours and the urine was red.  Physical examination shows conjunctival pallor but is otherwise normal.  Laboratory studies are as follows:

Urinalysis shows proteinuria and hematuria.  Which of the following mechanisms is the most likely cause of this patient’s condition?

A 46-year-old previously healthy woman comes to the emergency department due to 4 days of intermittent fever, abdominal pain, and vomiting.  For the past 2 days, she has also had decreased urine output, skin rash, and progressive lethargy.  Temperature is 38.3 C (101 F), blood pressure is 130/80 mm Hg, and pulse is 100/min.  There is a scattered petechial rash, facial puffiness, and 1+ bilateral pedal edema on physical examination.  Laboratory results show hemoglobin of 8.9 g/dL with elevated reticulocyte count and a platelet count of 26,000/mm³.  Bleeding time is prolonged; PT and activated PTT are normal.  The peripheral blood smear shows schistocytes and reduced platelets with presence of giant forms.  Blood urea nitrogen is 46 mg/dL and serum creatinine is 2.3 mg/dL.  Urinalysis is positive for proteinuria and hematuria.  Which of the following is most likely to be seen on this patient’s renal biopsy?