Pertinent Findings: The physical examination was remarkable for the presence of thickened, scaly areas (actinic keratosis) and hyperpigmented areas on skin exposed to ultraviolet (UV) radiation from the sun. Small dilated blood vessels (telangiectasia) were also seen. Tissue from several sites on his face was biopsied, and two were later determined to be squamous cell carcinomas.
Diagnosis: AZ has xeroderma pigmentosum, a rare defect in nucleotide excision repair of DNA.
Treatment: Protection from sunlight through use of sunscreens such as protective clothing that reflect UV radiation and chemicals that absorb it is essential. Frequent skin and eye examinations are recommended.
Prognosis: Most patients with xeroderma pigmentosum die at an early age from skin cancers. However, survival beyond middle age is possible.
Case-Related Questions: Choose the ONE best answer.
Q1. Which of the following statements about DNA repair mechanisms is correct? DNA repair:
A. is performed only by eukaryotes.
B. of double-strand breaks is error free.
C. of mismatched bases involves repair of the parental strand.
D. of UV radiation–induced pyrimidine dimers involves removal of a short oligonucleotide containing the dimer.
E. of uracil produced by the deamination of cytosine requires the actions of endo-and exonucleases to remove the uracil base.
Q2. Which one of the following statements about DNA synthesis (replication) is correct? Replication:
A. in both eukaryotes and prokaryotes requires an RNA primer.
B. in eukaryotes requires condensation of chromatin.
C. in prokaryotes is accomplished by a single DNA polymerase.
D. is initiated at random sites in the genome.
E. produces a polymer of deoxyribonucleoside monophosphates linked by 5′→3′-phosphodiester bonds. . What is the difference between DNA proofreading and repair?
Case 6: Dark Urine and Yellow Sclerae
Patient Presentation: JF is a 13-year-old boy who presents with fatigue and yellow sclerae.
Focused History: JF began treatment ~4 days ago with a sulfonamide antibiotic and a urinary analgesic for a urinary tract infection. He had been told that his urine would change color (become reddish) with the analgesic, but he reports that it has gotten darker (more brownish) over the last 2 days. Last night, his mother noticed that his eyes had a yellow tint. JF says he feels as though he has no energy.
Pertinent Findings: The physical examination was remarkable for JF’s pale appearance, mild scleral icterus (jaundice), mild splenomegaly, and increased heart rate (tachycardia). JF’s urine tested positive for hemoglobin (hemoglobinuria). A peripheral blood smear reveals a lower-than-normal number of red blood cells (RBC), with some containing precipitated hemoglobin (Heinz bodies; see image at right), and a higher-than-normal number of reticulocytes (immature RBC). Results of the complete blood count (CBC) and blood chemistry tests are pending.
Diagnosis: JF has glucose 6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder that causes hemolysis (RBC lysis).
Treatment: G6PD deficiency can result in a hemolytic anemia in affected individuals exposed to oxidative agents. JF will be switched to a different antibiotic. He will be advised that he is susceptible to certain drugs (for example, sulfa drugs), foods (fava or broad beans), and certain chemicals (for example, naphthalene), and must avoid exposure to them.
Prognosis: In the absence of exposure to oxidative agents, G6PD deficiency does not cause mortality or significant morbidity.
Case-Related Questions: Choose the ONE best answer.