Review Question - QID 106610

This patient is presenting with symptoms consistent with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Glutathione reductase deficiency causes a similar clinical picture and has similar pathophysiology, as both result from defects in the HMP shunt and fail to produce NADPH.

This patient is an immunocompromised HIV patient (CD4 count 149) who has become infected with pneumocystis jiroveci pneumonia (PJP/PCP) causing a diffuse interstitial pneumonia. The first-line treatment of PCP is trimethoprim-sulfamethoxazole. Sulfonamides are a known precipitant of hemolytic crises in G6PD deficiency. G6PD deficiency is an X-linked recessive disorder with an increased prevalence among African Americans. It causes a decrease in NADPH in red blood cells, which leads to hemolytic anemia due to poor RBC defense against oxidizing agents such as fava beans, sulfonamides, and primaquine. This can lead to a hemolytic crisis such as this patient is experiencing. Glutathione reductase deficiency would cause similar symptoms, as this would also result in an HMP shunt defect and prevent NADPH production similar to as occurs in G6PD deficiency (Illustration A).

Frank reviews the diagnosis and management of G6PD deficiency. G6PD deficiency, the most common enzyme deficiency worldwide, causes a spectrum of disease including neonatal hyperbilirubinemia, acute hemolysis, and chronic hemolysis. Furthermore, acute hemolysis is caused by exposure to an oxidative stressor in the form of an infection, oxidative drug, or fava beans, so treatment is geared toward avoidance of these and other stressors.

Ozcicek et al. examine the activities of G6PD, 6-phosphogluconate dehydrogenase, and glutathione reductase in patients with iron deficiency anemia (IDA) to ascertain if additional oxidative stress is observed. They compare 102 premenopausal women with IDA to 88 healthy control subjects. The authors find that the plasma glutathione reductase levels of premenopausal women with IDA were higher compared to healthy subjects. They postulate this could be secondary to erythrocyte protection against oxidative stress commonly seen in IDA.

Figure A is a chest radiograph demonstrating increased opacification in the bilateral lower lung fields, characteristic of PCP. Figure B demonstrates PJP/PCP from a bronchoalveolar lavage; note the characteristic cystic structure. Figure C represents the characteristic Heinz bodies, oxidized hemoglobin which precipitates in red blood cells, seen in G6PD deficiency. Illustration A is a graphic representation of the glutathione reductase pathway.

Incorrect Answers:
Answer 2: Galactokinase deficiency is a relatively mild condition that causes the accumulation of galactitol in the blood. It may present initially with infantile cataracts or a failure to track objects.
Answer 3: Ornithine transcarbamolyase deficiency is the most common urea cycle disorder and interferes with the body's ability to eliminate ammonia. It presents with increased orotic acid in the blood and urine as well as symptoms of hyperammonemia.
Answer 4: Carnitine deficiency causes the inability to transport long chain fatty acids into mitochondria, leading to a toxic accumulation. This results in weakness, hypotonia, and hypoketotic hypoglycemia.
Answer 5: Cystathionine synthase deficiency causes homocystinuria. This manifests as mental retardation, osteoporosis, tall stature, and downward lens subluxation.