The OtoDx™ Aminoglycoside
Hypersensitivity Test, #327

The ototoxic effects of aminoglycoside antibiotics have long been recognized. Recent studies show that patients who carry a certain mutation in their mitochondrial genome, known as the A1555G mutation, have an increased susceptibility to the ototoxic effects of these drugs. Identifying patients who have this mutation is critical, since the hearing loss can be prevented in most patients if aminoglycoside antibiotics are avoided.^1-4

Research has shown that even one dose of aminoglycoside antibiotics has caused hearing loss in A1555G individuals.⁶ Additionally, since mitochondrial DNA is inherited exclusively from mothers, maternal family members of A1555G positive patients will likely have this mutation and the associated aminoglycoside hypersensitivity. ^1-4

The hearing loss associated with the A1555G mutation is non-syndromic, sensorineural, and symmetric. It originates in the inner ear and does not appear to affect the cochlear nerve. ⁴ The A1555G mutation occurs in the 12S ribosomal RNA gene in the mitochondria, but the mechanism of interaction between the mutant gene and antibiotics that leads to hearing loss is not yet fully understood.⁷

Identify hypersensitive patients before they are placed at risk of hearing loss

• The A1555G mutation is known to cause aminoglycoside hypersensitivity, also known as antibiotic-induced deafness. ^1-9 
• Patients with the A1555G mutation should avoid the use of aminoglycoside antibiotics. ^1-9 
• A single dose of aminoglycosides may be ototoxic to these patients. ⁶  
• 100% of maternal family members are also at risk for sensorineural hearing loss. ¹ 
• A1555G mutations can also cause non-syndromic sensorineural hearing loss even in the absence of aminoglycoside exposure. ^4,7 
• Testing is critical for obtaining the best patient outcomes:
  • Individuals with A1555G mutations should be identified before starting aminoglycoside antibiotics. 
  • Many A1555G positive patients can avoid hearing loss if protected from aminoglycoside exposure. ^1-9
     
• Athena's OtoDx Aminoglycoside Hypersensitivity Test, #327 can identify your patients with this mutation.

References

1. Fischel-Ghodsian, N. et al., Mitochondrial Ribosomal RNA Gene Mutation in a Patient with Sporadic Aminoglycoside Ototoxicity. J. Otolaryngol 1993; 14:339-403.
2. Prezant, T. R. et al., Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genet 1993; 4(3):289-294.
3. El-Schahawi, M. et al., Two large Spanish pedigrees with nonsyndromic sensorineural deafness and the mtDNA mutation at nt 1555 in the 12S rRNA gene: Evidence of heteroplasmy. Neurology 1997; 48:453-456.
4. Estivill, X. et al., Familial Progressive Sensorineural Deafness Is Mainly Due to the mtDNA Al555G Mutation and Is Enhanced by Treatment with Aminoglycosides. Am. J. Hum. Genet 1998; 62:27-35.
5. Fischel-Ghodsian, N. Mitochondrial Deafness Mutations Reviewed. Human Mutation 1999; 13:261-270.
6. Usami, S. et al., Sensorineural Hearing Loss Associated with the Mitochondrial Mutations. Adv. Otorhinolaryngol 2000; 56:203-211.
7. Usami, S. et al., Genetic and Clinical Features of Sensorineural Hearing Loss Associated with the 1555 Mitochondrial Mutation. Laryngoscope 1997; 107:483-90.
8. Guan, Min-Xin. et al., A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity. Human Molecular Genetics 2000; 9(12): 1787-1793.
9. Hutchin, T. P. et al., Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromic sensorineural hearing impairment. J Med Genet 2001; 38:229-231.