Aminoglycoside-induced deafness


Aminoglycoside-induced deafness (AID) refers to the hearing loss that occurs in some people taking aminoglycosides, a type of antibiotic. Aminoglycosides, including streptomycin, gentamicin, kanamycin, tobramycin, and neomycin, are used to treat bacterial infections. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacter bacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most frequent use of aminoglycosides is for serious infections such as septicemia, complicated intra-abdominal infections, complicated urinary tract infections, and respiratory tract infections.
A single genetic mutation in the MTRN1 gene, which encodes for a type of ribosomal ribonucleic acid (RNA), predisposes individuals to aminoglycoside-induced deafness. The MTRN1 gene is located within the mitochondrial deoxyribonucleic acid (DNA) and is passed on only from mother to child. Mitochondrial DNA is located in organelles called mitochondria, which are responsible for generating most of the cell's energy supply. Evidence has shown that even a single dose of an aminoglycoside antibiotic results in irreversible hearing loss in individuals with this mutation. However, the hearing loss is not dependent on aminoglycoside exposure. Some cases of AID may be caused by other genetic mutations. In about one-third of people who develop AID, a genetic mutation is present.
Mitochondria are known as the "power houses" of cells that convert energy from food into a form that cells can use. While most of the DNA in the human body is contained in chromosomes inside the nucleus of the cell, the mitochondria contain 37 genes, all of which are necessary for normal mitochondrial function. Mitochondrial genes are inherited, or passed down among family members, from mother to child. Only maternal mitochondrial DNA is inherited.
Researchers believe that the defective MTRN1 gene causes improper production of certain cells, called hair cells, in the cochlea, a part of the ear necessary for hearing. The genetic mutation associated with AID is present in about 1% of the U.S. population.
About 40% of people with a mutated MTRN1 gene who have not been treated with aminoglycosides develop hearing loss by age 30. In people over age 65, this proportion increases to about 80%.
A genetic mutation in the MTRN1 gene is inherited, or passed down among family members, in an autosomal dominant pattern, meaning that only one copy of the defective gene is necessary for the susceptibility to be present. This mutation seems to be inherited from the mother, although there have been rare cases in which the father appears to have passed on the genetic mutation. Mitochondrial DNA is passed on from mother to child as a single circular piece of DNA. Therefore, only one copy of mitochondrial DNA is inherited.

Related Terms

AID, aminoglycoside, aminoglycoside ototoxicity, deafness, deafness streptomycin-induced, hearing loss, mitochondrial DNA, mitochondrial mutations, MTCO1, MTRN1, ototoxicity, streptomycin ototoxicity.