Related Terms

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

Background

• 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.

Risk Factors

• Exposure to aminoglycoside antibiotics can increase an individual's risk of developing aminoglycoside-induced deafness (AID). Evidence has shown that even a single dose of aminoglycoside antibiotic results in irreversible hearing loss in individuals with a mutation in the MTRN1 gene. However, hearing loss is not always dependent on aminoglycoside exposure. Some cases of AID may also be caused by other genetic mutations. In about one-third of people who develop AID, a genetic mutation is present. Furthermore, if an individual's mother has a defective MTRN1 gene, he or she is at increased risk for developing AID, because the MTRN1 gene is located in the mitochondrial DNA, which is passed on from mother to child. Individuals who inherit this defective gene may lose their hearing even if they are not exposed to aminoglycoside antibiotics. About 40% of individuals with the mutation who have not received these drugs develop hearing loss by age 30, and in people over age 65 with the mutation, this proportion increases to 80%. AID appears to affect males and females and all races and ethnicities equally.

Causes

• Aminoglycoside-induced deafness (AID) may be dose dependent, meaning that the risk of AID increases as the dose of aminoglycosides increases. AID may also be unrelated to dose and instead be caused by a genetic predisposition, meaning that an individual must have a mutated form of the MTRN1 gene.

• Individuals are susceptible to AID if they have a genetic mutation or defect in the mitochondrial MTRN1 gene. The MTRN1 gene is located within mitochondrial DNA. The AID mutation is therefore transmitted by maternal inheritance, as mitochondrial DNA is passed down only from mother to child. Mitochondrial DNA is the DNA located in organelles called mitochondria, which are responsible for generating most of the cell's energy supply. Evidence has shown that a single dose of an aminoglycoside antibiotic results in irreversible hearing loss in individuals with this mutation. The genetic mutation associated with AID is present in about 1% of the population. AID can occur even if the mother does not have AID, since this mutated gene in the mitochondrial DNA can occur spontaneously. However, if a mother carries the genetic mutation in her mitochondrial DNA, the child will certainly inherit the mutation. There is a lack of information on whether individuals can be asymptomatic carriers of AID.

• Mitochondria are known as the "power houses" of the 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, which are pieces of DNA that carry many genes inside the nucleus of the cell, the mitochondria contain 37 genes, all of which are necessary for normal mitochondrial functioning. Researchers believe that the defective MTRN1 gene causes improper production of hair cells in the cochlea, a necessary part of the ear for hearing. Information on the exact mechanisms of how the gene becomes defective is currently lacking. Some cases of AID may also be caused by other genetic mutations, but little is known about this.

Signs and Symptoms

• Aminoglycoside-induced deafness (AID) is characterized by profound hearing loss. The onset and severity of hearing loss may vary, even among members of the same family. AID is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic. However, individuals who inherit the defective MTRN1 gene may lose their hearing even if they are not exposed to aminoglycoside antibiotics. About 40% of individuals with the mutation who have not received these drugs develop hearing loss by age 30. By age 65, this proportion increases to 80%.

• Because there are no other symptoms associated with AID, the only factor that can distinguish AID from age-related deafness is a family history of the disorder that shows a pattern of maternal inheritance, and that onset of hearing loss occurs following administration of an aminoglycoside antibiotic.

Diagnosis

• General: Diagnosis of AID is usually based on a hearing test and genetic testing in order to distinguish it from other causes of hearing loss. A review of the patient's medical history would be conducted to determine if he or she had recently taken an aminoglycoside antibiotic.

• Hearing test: An audiogram, a type of hearing test, may help diagnose AID. During an audiogram, the patient wears headphones and is exposed to various sounds of different pitches and frequencies. The patient is asked to identify each time a sound is heard. The audiologist may also say various words aloud to evaluate the patient's hearing ability.

• Genetic testing: If AID is suspected, a DNA test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the MTRN1 gene. If this defect is detected, a positive diagnosis is made.

• Prenatal DNA testing: If there is a family history of AID, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose AID. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional before doing so.

• During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus. A small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about 0.25%-0.5% in patients who undergo this procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

• During CVS a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the MTRN1 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Treatment

• General: Aminoglycoside-induced deafness (AID) is not a curable condition. Instead, treatment focuses on managing hearing loss. AID is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic. About 40% of individuals with a mutation in the MTRN1 gene who have not received aminoglycoside antibiotics develop hearing loss by age 30. By age 65, this proportion increases to 80%.

• Hearing aids: People with AID who experience hearing loss may benefit from hearing aids. These battery-operated devices allow people to hear a greater range of sounds by amplifying sounds and are available in three basic styles: behind the ear, in the ear, and inside the ear canal. Patients should talk to their healthcare provider to determine the type of hearing aid that is best for them. A behind-the-ear device is used for mild-to-profound hearing loss. The device is worn behind the ear and is attached to a plastic ear mold inside the outer ear. In-the-ear hearing aids are worn inside the outer ear and are used for mild-to-severe hearing loss. Canal hearing aids are smaller hearing aids that fit inside the patient's ear canal. They are used for mild-to-moderately severe hearing loss.

• If hearing loss is severe, patients may benefit from cochlear implants. These electronic devices are surgically implanted inside the ears. Unlike a hearing aid, which amplifies sound, a cochlear implant compensates for damaged parts of the inner ear.

Integrative Therapies

• Currently, scientific evidence on the use of integrative therapies for the treatment or prevention of aminoglycoside-induced deafness (AID) is lacking.

Prevention

• General: Aminoglycoside-induced deafness (AID) may be prevented by obtaining a rigorous family history and undergoing molecular testing. Once people who have the defective MTRN1 gene are identified, they can be educated to avoid exposure to aminoglycoside antibiotics, including streptomycin, gentamicin, kanamycin, tobramycin, and neomycin. However, some individuals with the genetic mutation can develop hearing loss even without exposure to aminoglycoside antibiotics.

• Genetic testing and counseling: Individuals who have AID may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with family histories of AID, but who have not been diagnosed with the syndrome themselves, may meet with a genetic counselor to determine whether they carry the defective MTRN1 gene.

• If an individual who has not yet been diagnosed with AID is found to have inherited one of the defective genes, he or she may undergo genetic counseling before conceiving a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and CVS.

• PGD may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective MTRN1 gene, and only the embryos that are not affected may be selected for implantation. Because AID can be detected in a fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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