A 4-day-old girl is brought to the office for a routine newborn visit.  She was born at 39 weeks gestation via an uncomplicated spontaneous vaginal delivery to a gravida 5 para 5 woman.  The patient has been breastfed exclusively but has had increasing difficulty feeding over the past 24 hours.  Her parents say that she is “too sleepy to eat” and has been vomiting.  The infant has 3 healthy, living siblings; a brother died in infancy from “low sugar in his blood.”  Physical examination is notable for tachypnea and signs of dehydration.  The patient is responsive to painful stimuli only.  After acute treatment and stabilization, urine testing reveals a significantly elevated methylmalonic acid level.  Which of the following sets of laboratory findings is most likely to be found in this patient?

A 3-year-old boy who recently immigrated to the United States is brought to the physician by his parents because he has not yet begun to walk or speak.  Assessment of his developmental milestones shows severe intellectual disability.  He dies 6 months later from refractory seizures resulting in respiratory failure.  Autopsy shows pallor of the substantia nigra, locus ceruleus, and vagal nucleus dorsalis.  The underlying condition responsible for this patient’s death is most likely caused by a deficiency of which of the following enzymes?

As part of an experiment, healthy volunteers undergo a 12-hour fast and then drink a solution containing radiolabeled alanine.  Consecutive blood samples are drawn every 15 minutes for the next 3 hours.  Initial blood samples detect the radiolabeled alanine, but analysis of later samples shows that the radiotracer is present in blood primarily in the form of glucose.  Before alanine can be converted to glucose, its amino group is transferred to which of the following?

A 4-day-old boy born to a 23-year-old woman is brought to the office for evaluation of poor feeding and vomiting.  The pregnancy was uneventful and the mother had a normal delivery.  Family history is noncontributory.  The patient’s temperature is 37.2 C (99 F), blood pressure is 60/30 mm Hg, pulse is 110/min, and respirations are 56/min.  Physical examination reveals a lethargic newborn with exaggerated deep tendon reflexes and clonus.  Further investigation reveals that the patient has an inherited condition that results in impaired transport of ornithine from the cytosol to the mitochondria.  Nutritional restriction of which of the following substances can improve this patient’s condition?

A 7-day-old neonate born to a 28-year-old woman is brought to the office due to progressive lethargy, vomiting, and poor feeding.  The mother reports an uneventful pregnancy and perinatal course.  She exclusively breastfeeds the infant and has no medical problems in any of her other children.  On examination, the infant is somnolent and dehydrated with decreased muscle tone.  Laboratory studies reveal metabolic acidosis with an elevated anion gap, ketosis, and hypoglycemia.  Further evaluation reveals a markedly elevated propionic acid level due to defective conversion of propionyl-CoA to methylmalonyl-CoA.  This patient is most likely unable to use which of the following amino acids for energy production?

A 5-month-old boy is brought to the office by his parents who are concerned that he has developmental delay.  He has 3 older siblings, and the parents report that his siblings were much more active and interactive at the boy’s age.  The family has just moved to the United States from South America and did not have consistent primary care previously.  Physical examination shows that the boy is unable to roll from front to back or back to front and does not seem to recognize his parents.  Comprehensive laboratory evaluation reveals impaired tetrahydrobiopterin synthesis.  Which of the following is most likely deficient in this patient?

A 3-year-old boy is brought to the office due to abnormal motor development.  He was born at 40 weeks gestation and had an unremarkable perinatal course.  The boy developed normally during the first year of life.  However, for the past 2 years, he has had progressive bilateral leg stiffness and abnormal involuntary movements.  His cognitive and motor development is also delayed.  There is no significant family history of neurological or muscular disorders.  The patient’s height, weight, and head circumference are below the 3rd percentile.  Examination shows bilateral spastic paresis of his lower extremities and frequent choreoathetoid movements.  Comprehensive laboratory testing reveals significantly elevated arginine levels in plasma and cerebrospinal fluid.  The deficient enzyme in this patient is normally involved in the production of which of the following?

A 38-year-old man comes to the office due to pain in multiple joints.  He has a 5-year history of lumbar pain and a 2-year history of bilateral knee pain.  The patient works in construction and his pain is worst after a long day on his feet.  He has taken ibuprofen intermittently, but the pain is no longer tolerable.  The patient has a paternal aunt with osteoarthritis.  Physical examination shows blue-black spots on his sclerae and diffuse darkening of the auricular helices.  Which of the following is the most likely cause of this patient’s arthritis?

A 2-year-old boy is brought to the office by his parents.  He is currently toilet-training during the day and at nighttime.  After he urinated in the toilet last night, his parents forgot to flush the toilet and noticed that the boy’s urine turned black overnight.  The child has no significant past medical history and takes no medications.  He can say 2-word sentences, follow 2-step directions, and jump with 2 feet off the ground.  Examination shows a well-nourished child with no swelling or tenderness of any joints.  Urinalysis results are as follows:

Which of the following conversion pathways is most likely deficient in this patient?

A 12-year-old boy is brought to the emergency department with severe chest pain.  He has had intermittent substernal chest pain for the past few months that typically occurs after heavy activity.  The boy’s activities have been limited due to the chest pain, and he is no longer able to play on the soccer team.  The patient does not use tobacco or illicit drugs.  His temperature is 36.7 C (98 F), blood pressure is 130/80 mm Hg, pulse is 132/min, respirations are 24/min, and pulse oximetry is 98% on room air.  BMI is 17 kg/m².  Physical examination shows an anxious-appearing boy with a rapid but regular pulse.  No abnormalities are seen.  Troponin is elevated, and ECG reveals ST segment elevations in leads II, III, and aVF.  After acute stabilization and treatment, further laboratory workup shows an increased serum methionine level.  Which of the following amino acids is most likely essential in this patient?

A 5-year-old boy with developmental delay is brought to the office due to difficulty “seeing the board” at school.  Examination shows a boy with a tall, thin habitus with elongated limbs.  Funduscopy shows bilateral lens subluxation.  Four years later, the patient dies suddenly of a massive cerebrovascular accident.  Autopsy shows middle cerebral artery thrombosis and old renal infarcts.  His parents wish to know if anything could have been done to have prevented his death.  Which of the following would have been the most appropriate supplementation for this patient?

A 3-day-old boy is brought to the emergency department due to vomiting, poor feeding, and progressively worsening lethargy.  The parents report that his diapers have a sweet smell unlike what they experienced with their older children.  The mother and infant were discharged from the hospital yesterday after a normal pregnancy and spontaneous vaginal delivery.  The mother is exclusively breastfeeding.  Her other 2 children are healthy and have no medical conditions.  On physical examination, the infant is lethargic with dry mucous membranes and generalized hypertonia.  Which of the following should be restricted from this infant’s diet?

A 4-day-old infant is brought to the emergency department due to abnormal movements.  The patient has had intermittent episodes of tonic posturing over the past 3 hours as well as vomiting, poor feeding, and irritability for the past 2 days.  The mother also reports that the infant’s diapers smell like caramelizing sugar.  There are no known medical conditions in the family, but the mother’s sister died “sometime in the first year” of life from unknown causes.  On examination, the patient is lethargic and demonstrates intermittent posturing and increased generalized muscle tone.  Laboratory evaluation of plasma and urine samples confirms the suspected diagnosis.  This patient is most likely deficient in an enzyme that requires which of the following substances?

A group of investigators is studying the regulation of catecholamine synthesis in response to severe stress.  In the experiments, subject rats are randomly assigned to either an experimental or a control group.  The experimental rats undergo resection of the pituitary gland, and the control rats undergo craniotomy without pituitary resection.  The experimental animals are subsequently found to have decreased production of epinephrine by the adrenal medulla and cortisol from the adrenal cortex compared with the control animals.  Decreased activity of which of the following enzymes is most likely responsible for the lower epinephrine in the experimental animals?

A 2-year-old boy is brought to the emergency department with fever, vomiting, and sleepiness.  He had several episodes of emesis this morning, and his mother was unable to wake him from his afternoon nap.  The boy has had mild rhinorrhea and fever for the past 3 days.  Since the newborn period, the parents say that the patient has had multiple illnesses characterized by vomiting and sleepiness.  Prior laboratory testing revealed increased blood ammonia levels during these episodes and markedly increased orotic acid excretion in the urine.  Physical examination shows a tachypneic boy who is unresponsive to all stimuli.  Which of the following enzymes is most likely to be deficient in this patient?