A 50-year-old man came to the doctor with painful blisters on the backs of his hands. He worked as a golf instructor and mentioned that the blisters appeared after the golf season started. He denied recent exposure to common skin irritants. The patient had a history of partial complex seizure disorder, which began about 3 years ago after a head injury. Since the onset of the seizure disorder, he had been taking only one medication called phenytoin. He admitted to consuming an average of 18 12-oz cans of beer per week. The patient's urine had a reddish orange color. Cultures taken from the skin lesions did not show any growth of organisms. A 24-hour urine collection revealed elevated uroporphyrin levels (1,000 mg; normal, <27 mg). The most probable diagnosis is porphyria cutanea tarda (E). This condition is associated with a deficiency in uroporphyrinogen III decarboxylase (UROD). However, the clinical manifestation of this enzyme deficiency is affected by liver damage caused by environmental factors like ethanol and infectious agents such as hepatitis B virus. Sunlight exposure can also trigger the symptoms. Typically, the disease presents in the fourth or fifth decade of life. Accumulation of porphyrins leads to cutaneous symptoms and urine that appears red to brown. Phenytoin treatment for the seizure disorder resulted in increased synthesis of δ-aminolevulinic acid synthase and, consequently, increased production of uroporphyrinogen, which is the substrate of the deficient UROD. The laboratory and clinical findings do not align with other types of porphyrias.

A patient arrives with jaundice, abdominal pain, and nausea. The clinical laboratory results are as follows:

- Bilirubin: Elevated levels
- Urine bilirubin: Present
- Stool color: Pale
- Urinary urobilinogen: Not present

The most likely cause of the jaundice is decreased secretion of bile into the intestine (C). The data suggests an obstructive jaundice where a blockage in the common bile duct hinders the release of bile containing conjugated bilirubin into the intestine. As a result, the conjugated bilirubin regurgitates into the blood (causing conjugated hyperbilirubinemia). The excess conjugated bilirubin is excreted in the urine, darkening its color. Since the source of urinary urobilinogen is intestinal urobilinogen, its absence is expected. The other options do not match the given data.

A 2-year-old child was taken to the pediatrician for gastrointestinal issues. The parents reported that the child had been lethargic for the past few weeks. Laboratory tests revealed a microcytic, hypochromic anemia, and elevated blood lead levels. In the liver of this child, the enzyme most likely to have higher-than-normal activity is δ-aminolevulinic acid synthase (A).
1.2. A 50-year-old man presented with painful blisters on the backs of his hands. He was a golf instructor and indicated that the blisters had erupted shortly after the golfing season began. He did not have recent exposure to common skin irritants. He had partial complex seizure disorder that had begun ~3 years earlier after a head injury. The patient had been taking phenytoin (his only medication) since the onset of the seizure disorder. He admitted to an average weekly ethanol intake of ~18 12-oz cans of beer. The patient’s urine was reddish orange. Cultures obtained from skin lesions failed to grow organisms. A 24-hour urine collection showed elevated uroporphyrin (1,000 mg; normal, <27 mg). The most likely diagnosis is:
A. acute intermittent porphyria.
B. congenital erythropoietic porphyria.
C. erythropoietic protoporphyria.
D. hereditary coproporphyria.
E. porphyria cutanea tarda.
Correct answer = E. The disease is associated with a deficiency in uroporphyrinogen III decarboxylase (UROD), but clinical expression of the enzyme deficiency is influenced by hepatic injury caused by environmental (for example, ethanol) and infectious (for example, hepatitis B virus) agents. Exposure to sunlight can also be a precipitating factor. Clinical onset is typically during the fourth or fifth decade of life. Porphyrin accumulation leads to cutaneous symptoms and urine that is red to brown. Treatment of the patient’s seizure disorder with phenytoin caused increased synthesis of δaminolevulinic acid synthase and, therefore, of uroporphyrinogen, the substrate of the deficient UROD. The laboratory and clinical findings are inconsistent with other porphyrias.
21.3. A patient presents with jaundice, abdominal pain, and nausea. Clinical laboratory results are shown below.
What is the most likely cause of the jaundice?
A. Decreased hepatic conjugation of bilirubin
B. Decreased hepatic uptake of bilirubin
C. Decreased secretion of bile into the intestine
D. Increased hemolysis
Correct answer = C. The data are consistent with an obstructive jaundice in which a block in the common bile duct decreases the secretion of bile containing conjugated bilirubin (CB) into the intestine (stool will be pale in color). The CB regurgitates into the blood (conjugated hyperbilirubinemia). The CB is excreted in the urine (which darkens) and is referred to as urinary bilirubin. Urinary urobilinogen is not present because its source is intestinal urobilinogen, which is low. The other choices do not match the data.
1.4. A 2-year-old child was brought to his pediatrician for evaluation of gastrointestinal problems. The parents report that the boy has been listless for the last few weeks. Lab tests reveal a microcytic, hypochromic anemia. Blood lead levels are elevated. Which of the enzymes listed below is most likely to have higher-than-normal activity in the liver of this child?
A. δ-Aminolevulinic acid synthase
B. Bilirubin UDP glucuronosyltransferase
C. Ferrochelatase
D. Heme oxygenase
E. Porphobilinogen synthase