Glucose-6-phosphate dehydrogenase (G6PD) deficiency is inherited in an X-linked recessive fashion (Figure E).
This patient is a poorly compliant, most likely immunocompromised, HIV+ patient who has become infected with nocardia, a gram-positive, acid fast, aerobe known to cause pulmonary infections in immunocompromised hosts. The treatment for nocardia are sulfonamide antibiotics. Sulfonamides are a known precipitant of hemolytic crises in G6PD deficiency. G6PD deficiency is an X-linked recessive disorder with an increased prevalence among blacks. 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. Of note, G6PD deficiency is the most common enzyme deficiency worldwide. This is thought to be due to its ability to infer resistance to malaria. In regards to treatment of malaria, primaquine is the only available agent that targets the hypnozoites or dormant form of P. vivax. However, due to the lack of testing for G6PD deficiency in most of the developing world, is not used initially due to fears of precipitating hemolytic crisis.
Gomez et al. correlated the location of the mutation sites in G6PD with the resulting phenotypes. To do this they studied four naturally occurring G6PD variants: Yucatan, Nashville, Valladolid, and Mexico City. It was found that the mutations corresponding to more severe phenotypes are related to the structural NADP+ binding region in G6PD.
Frank reviews the diagnosis and management of G6PD deficiency. He states glucose-6-phosphate dehydrogenase deficiency, the most common enzyme deficiency worldwide, causes a spectrum of disease including neonatal hyperbilirubinemia, acute hemolysis, and chronic hemolysis. Furthermore, he states 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.
Figures A-D are described below in the incorrect answer section.
Answer 1: Figure A is a pedigree that represents an autosomal recessive pattern of inheritance.
Answer 2: Figure B is a pedigree that represents an maternal pattern of inheritance (as seen in mitochondrial diseases).
Answer 3: Figure C is a pedigree that represents an autosomal dominant pattern of inheritance.
Answer 4: Figure D is a pedigree that represents an autosomal dominant pattern of inheritance.
Gómez-Manzo S, Terrón-Hernández J, De la Mora-De la Mora I, González-Valdez A, Marcial-Quino J, García-Torres I, Vanoye-Carlo A, López-Velázquez G, Hernández-Alcántara G, Oria-Hernández J, Reyes-Vivas H, Enríquez-Flores S. The stability of G6PD is affected by mutations with different clinical phenotypes. Int J Mol Sci. 2014 Nov 17;15(11):21179-201. doi: 10.3390/ijms151121179. PubMed PMID: 25407525; PubMed Central PMCID: PMC
PMID:25407525 (Link to Abstract)
Frank JE. Diagnosis and management of G6PD deficiency. Am Fam Physician. 2005 Oct 1;72(7):1277-82. Review. PubMed PMID: .
PMID:16225031 (Link to Abstract)