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Aminoglycoside-induced deafness
This condition causes hearing loss or deafness after exposure to aminoglycoside antibiotics, typically affecting those with specific changes in their mitochondrial DNA. It can impact individuals of any age who receive these medications.
Overview
Aminoglycoside-induced deafness refers to hearing loss or deafness that develops after an individual is treated with a class of antibiotics called aminoglycosides. This reaction does not affect everyone who takes these antibiotics; it primarily occurs in individuals who have an underlying genetic susceptibility. The condition is permanent and typically affects both ears [PMID:24817112].
Aminoglycoside antibiotics, such as gentamicin, amikacin, and streptomycin, are commonly used to treat severe bacterial infections when other antibiotics may not be effective. While these medications are important for certain medical conditions, for those with a genetic predisposition, exposure can lead to irreversible hearing damage. The genetic change often makes the inner ear cells more vulnerable to the toxic effects of these drugs.
Symptoms & clinical features
The primary symptom of aminoglycoside-induced deafness is a sudden or rapid onset of hearing loss. This usually begins shortly after a person has received aminoglycoside antibiotics, sometimes even after only a few doses [PMID:24817112]. The hearing loss is typically permanent and can range from partial to profound deafness.
In some cases, individuals may also experience tinnitus, which is a ringing or buzzing sound in the ears, and occasionally problems with balance, as the inner ear also plays a role in balance. The severity of hearing loss can vary, but it commonly affects both ears symmetrically.
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Affected organs
Aminoglycoside-induced deafness primarily affects the inner ear, specifically the specialised hair cells within the cochlea. The cochlea is the part of the ear responsible for converting sound vibrations into nerve impulses that the brain interprets as sound. Damage to these hair cells is irreversible and leads to permanent hearing loss.
While the main impact is on hearing, structures involved in balance, also located in the inner ear, can sometimes be affected. This might lead to issues with balance or dizziness in some individuals, though hearing loss is the more common and prominent symptom.
Risks & severity
The risk of developing aminoglycoside-induced deafness is directly linked to an individual's genetic susceptibility and exposure to aminoglycoside antibiotics. Without the genetic predisposition, this type of deafness does not typically occur. The exact prevalence of this genetic susceptibility within the general population is estimated to be around 0.2% in the UK [PMID:33671239].
The severity of hearing loss can vary among affected individuals, but it is generally permanent and can be profound. The onset of hearing loss can be rapid, even after a short course of medication. Once hearing loss has occurred, it is irreversible. The condition does not typically progress further if there is no subsequent exposure to aminoglycosides.
Genetic causes
Aminoglycoside-induced deafness is caused by specific changes in the mitochondrial DNA (mtDNA). Mitochondria are often called the 'powerhouses' of our cells, and they contain their own small circular piece of DNA distinct from the DNA found in the cell's nucleus.
One particular change in mtDNA, typically denoted as m.1555A>G, makes the individual significantly more susceptible to the ototoxic, or ear-damaging, effects of aminoglycoside antibiotics. This change alters a component of the mitochondrial ribosome, making it resemble the bacterial ribosome, which is the target of aminoglycoside antibiotics. When these antibiotics are present, they can inadvertently bind to the altered mitochondrial ribosomes in inner ear cells, disrupting protein production and leading to cellular damage and death, resulting in permanent hearing loss [PMID:24817112].
Inheritance pattern
Aminoglycoside-induced deafness follows a mitochondrial inheritance pattern. This means the genetic information is passed down exclusively from the mother to all her children.
Both males and females born to a mother with the genetic change in her mitochondrial DNA have a 100% chance of inheriting the change. However, only those who inherit the change and are then exposed to aminoglycoside antibiotics will develop hearing loss. Fathers with the genetic change do not pass it on to their children.
Diagnosis & testing
Diagnosis of aminoglycoside-induced deafness is typically suspected when hearing loss develops after exposure to aminoglycoside antibiotics. This is then confirmed through genetic testing to identify the specific mitochondrial DNA change, such as m.1555A>G.
In the UK, individuals suspected of having this condition, or those with a family history who may be at risk, can be referred to a clinical genetics service. Genetic testing for mitochondrial changes is available as part of the NHS Genomic Medicine Service (GMS) under specific R-codes for deafness and mitochondrial conditions. Genetic counsellors can provide information about testing and its implications.
Management & lifestyle
The most important aspect of managing aminoglycoside-induced deafness is prevention. If an individual is known to carry the predisposing genetic change, or if there is a family history of aminoglycoside-induced deafness, avoiding aminoglycoside antibiotics is crucial. This information should be clearly documented in an individual's medical records and communicated to all healthcare providers.
For individuals who have already developed hearing loss, management focuses on supportive care. This may include hearing aids or, in cases of profound deafness, cochlear implants to help restore some hearing sensation. Audiology services within the NHS can assess hearing loss and advise on appropriate devices. Genetic counselling is also important for affected individuals and their families to understand the inheritance pattern and risks for other family members.
UK care pathway
In the UK, individuals with suspected genetic hearing loss or a family history of aminoglycoside-induced deafness can be referred through their GP or an audiology specialist to a regional Clinical Genetics service within the NHS. These services offer genetic counselling and coordinate genetic testing as part of the NHS Genomic Medicine Service (GMS).
Genetic testing for deafness-related conditions, including mitochondrial causes like m.1555A>G, falls under specific R-codes within the GMS National Genomic Test Directory. A genetic counsellor can provide detailed information about the condition, inheritance patterns, and the implications of genetic testing for individuals and their families. This ensures families receive consistent and evidence-based information and support.
Frequently asked questions
Can I get tested for the genetic change?
Yes, if there's a family history of aminoglycoside-induced deafness or if you've experienced hearing loss after taking these antibiotics, your doctor can refer you to an NHS Clinical Genetics service for genetic testing. This can identify if you carry the specific mitochondrial genetic change.
If I have the genetic change, does it mean I will definitely go deaf?
No, carrying the genetic change for aminoglycoside-induced deafness does not guarantee hearing loss. It only means you are highly susceptible. Hearing loss will typically only occur if you are exposed to aminoglycoside antibiotics. Avoiding these medications is crucial for preventing deafness.
Which antibiotics should I avoid if I have this genetic change?
If you carry the genetic change for aminoglycoside-induced deafness, you should avoid all aminoglycoside antibiotics. Common examples include gentamicin, amikacin, streptomycin, and tobramycin. Always inform your healthcare providers about your genetic susceptibility before receiving any antibiotics.
Is the hearing loss reversible?
Unfortunately, the hearing loss caused by aminoglycoside-induced deafness is typically permanent and irreversible. The damage to the inner ear hair cells cannot usually be repaired. Management focuses on preventing further damage and providing support for existing hearing loss, such as hearing aids or cochlear implants.
Can fathers pass on this genetic change?
No, aminoglycoside-induced deafness follows a mitochondrial inheritance pattern, meaning the genetic change is passed exclusively from the mother to all her children. Fathers who carry the genetic change will not pass it on to their children.
References
- Cortopassi G, Hutchin T. A molecular and cellular hypothesis for aminoglycoside-induced deafness. Hearing research. 1994. PMID: 7961174
- Zhao H, Li R, Wang Q. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. American journal of human genetics. 2004. PMID: 14681830
- Chen J, Yang L, Yang A. Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees. Gene. 2007. PMID: 17698299
- Huang S, Xiang G, Kang D. Rapid identification of aminoglycoside-induced deafness gene mutations using multiplex real-time polymerase chain reaction. International journal of pediatric otorhinolaryngology. 2015. PMID: 25959403
- Yuan H, Chen J, Liu X. Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss. Biochemical and biophysical research communications. 2007. PMID: 17698030
- Bacino C, Prezant TR, Bu X. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995. PMID: 7550368
- Prezant TR, Agapian JV, Bohlman MC. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature genetics. 1993. PMID: 7689389
- Igumnova V, Veidemane L, Vīksna A. The prevalence of mitochondrial mutations associated with aminoglycoside-induced deafness in ethnic Latvian population: the appraisal of the evidence. Journal of human genetics. 2019. PMID: 30523288