Patient Presentation: RL is a 40-hour-old male with signs of cerebral edema.
Focused History: RL is the full-term product of a normal pregnancy and delivery. He appeared normal at birth. At age 36 hours, he became irritable, lethargic, and hypothermic. He fed only poorly and vomited. He also displayed tachypneic (rapid) breathing and neurologic posturing. At age 38 hours, he had a seizure.
Pertinent Findings: Respiratory alkalosis (increased pH, decreased CO2 [hypocapnia]), increased ammonia, and decreased blood urea nitrogen were found. An amino acid screen revealed that argininosuccinate was increased >60fold over baseline, and citrulline was increased 4-fold. Glutamine was elevated, and arginine (Arg) was decreased relative to normal.
Diagnosis: RL has a urea cycle enzyme defect with neonatal onset.
Treatment: Hemodialysis was performed to remove ammonia. Sodium phenylacetate and sodium benzoate were administered to aid in excretion of waste nitrogen, as was Arg. Long-term treatment will include lifelong limitation of dietary protein; supplementation with essential amino acids; and administration of Arg, sodium phenylacetate, and sodium phenylbutyrate.
Prognosis: Survival into adulthood is possible. The degree of neurologic impairment is related to the degree and extent of the hyperammonemia.
Case-Related Questions: Choose the ONE best answer.
Q1. Based on the findings, which enzyme of the urea cycle is most likely to be deficient in this patient?
A. Arginase
B. Argininosuccinate lyase
C. Argininosuccinate synthetase
D. Carbamoyl phosphate synthetase I
E. Ornithine transcarbamoylase Q2. Why is Arg supplementation helpful in this case?
Q3. In individuals with partial (milder) deficiency of urea cycle enzymes, the level of which one of the following would be expected to be decreased during periods of physiologic stress?
A. Alanine
B. Ammonia
C. Glutamine
D. Insulin
E. pH
Case 10: Calf Pain
Patient Presentation: CR is a 19-year-old female who is being evaluated for pain and swelling in her right calf.
Focused History: Ten days ago, CR had her spleen removed following a bicycle accident in which she fractured her tibial eminence, necessitating immobilization of the right knee. She has had a good recovery from the surgery. CR is no longer taking pain medication but has continued her oral contraceptives (OCP).
Pertinent Findings: CR’s right calf is reddish in color (erythematous) and warm to the touch. It is visibly swollen. The left calf is normal in appearance and is without pain. An ultrasound is ordered.
Diagnosis: CR has a deep venous thrombosis (DVT). OCP are a risk factor for DVT, as are surgery and immobilization.
Treatment (Immediate): Heparin and warfarin are administered.
Prognosis: In the 10 years following a DVT, about one third of individuals have a recurrence.
Case-Related Questions: Choose the ONE best answer.
Q1. A DVT is a blood clot that occludes the lumen of a deep vein, most commonly in the leg. Which of the following statements about the clotting cascade is correct?
A. A deficiency in factor (F)IX of the intrinsic pathway results in hemophilia A.
B. FIII of the extrinsic pathway is a serine protease.
C. Formation of the fibrin meshwork is referred to as primary hemostasis.
D. Thrombin proteolytically activates components of the extrinsic, intrinsic, and common pathways.