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Patient Presentation: RL, a male newborn, is showing signs of cerebral edema at 40 hours of age.
Focused History: RL was born at full term following a normal pregnancy and delivery. He displayed no abnormalities at birth. However, at 36 hours old, he began exhibiting irritability, lethargy, and hypothermia. RL showed poor feeding and vomiting. Additionally, he had rapid breathing (tachypnea) and neurologic posturing. By 38 hours old, RL experienced a seizure.
Pertinent Findings: RL's condition revealed respiratory alkalosis (increased pH and decreased CO2 [hypocapnia]), elevated ammonia levels, and decreased blood urea nitrogen. An amino acid screen showed a significant increase (>60-fold over baseline) in argininosuccinate and a four-fold increase in citrulline. Glutamine levels were elevated, while arginine (Arg) levels were lower than normal.
Diagnosis: RL is diagnosed with neonatal onset urea cycle enzyme defect.
Treatment: Hemodialysis was conducted to eliminate ammonia from RL's system. RL received sodium phenylacetate and sodium benzoate to aid in the excretion of waste nitrogen, along with arginine (Arg). Long-term treatment involves a restricted dietary protein intake, supplementation with essential amino acids, and administration of arginine (Arg), sodium phenylacetate, and sodium phenylbutyrate.
Prognosis: RL has the possibility of surviving into adulthood. The severity of neurologic impairment is dependent on the extent and severity of hyperammonemia.
Case-Related Questions: Choose the ONE best answer.
Q1. Based on the findings, which enzyme deficiency in the urea cycle is most likely present in this patient?
A. Arginase
B. Argininosuccinate lyase
C. Argininosuccinate synthetase
D. Carbamoyl phosphate synthetase I
E. Ornithine transcarbamoylase
Q2. Why is arginine (Arg) supplementation beneficial in this case?
Q3. In individuals with partial (milder) deficiency of urea cycle enzymes, which one of the following is expected to decrease during periods of physiologic stress?
A. Alanine
B. Ammonia
C. Glutamine
D. Insulin
E. pH
Case 10: Calf Pain
Patient Presentation: CR, a 19-year-old female, is currently being evaluated for pain and swelling in her right calf.
Focused History: CR underwent a splenectomy ten days ago due to a bicycle accident resulting in a fractured tibial eminence that required immobilization of her right knee. The surgical procedure was successful, and CR has recovered well. She no longer requires pain medication but continues to take oral contraceptives (OCP).
Pertinent Findings: CR's right calf appears reddish (erythematous), warm to the touch, visibly swollen, while her left calf shows no abnormalities or pain. An ultrasound has been ordered for further evaluation.
Diagnosis: CR has a deep venous thrombosis (DVT). The use of oral contraceptives (OCP), surgery, and immobilization are risk factors for DVT.
Treatment (Immediate): CR is administered heparin and warfarin.
Prognosis: Within 10 years of a DVT occurrence, approximately one third of individuals experience recurrence.
Case-Related Questions: Choose the ONE best answer.
Q1. A deep venous thrombosis (DVT) is characterized by a blood clot that obstructs the lumen of a deep vein, most commonly in the leg. Which statement accurately describes the clotting cascade?
A. Deficiency in factor (F)IX of the intrinsic pathway leads to hemophilia A.
B. FIII of the extrinsic pathway functions as a serine protease.
C. The formation of the fibrin meshwork is referred to as primary hemostasis.
D. Thrombin activates components of the extrinsic, intrinsic, and common pathways via proteolysis.

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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.