Aminoglycoside-induced deafness during treatment of acute leukaemia

Bitner‐Glindzicz, Maria; Osei-Lah, V; Colvin, I; Sirimanna, Tony; Lucas, D; Ardle, Breege Mac; Webb, David C.; Shankar, Ananth; Kingston, J. E.; Jenkins, Lucy; Rahman, Shamima

doi:10.1136/adc.2009.158220

Cited by 8 publications

(4 citation statements)

References 6 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, many people at risk of aminoglycoside-induced hearing loss are likely to have normal hearing if they have not been exposed to aminoglycosides and will not be suspected of being susceptible by any means other than genetic testing. Rapid genetic testing prior to aminoglycoside administration would be ideal in order to prevent avoidable deafness21 22 because those who have the mutation should be prescribed alternative antibiotics. Currently, all genetic screening is performed on an elective basis rather than in an acute situation because no rapid testing is available.…”

Section: Discussionmentioning

confidence: 99%

Hearing in 44–45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study

Rahman

Ecob²,

Costello³

et al. 2012

BMJ Open

View full text Add to dashboard Cite

Background: The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss).Objectives: To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the costebenefit argument for genetic testing prior to aminoglycoside administration.Design: Population-based cohort study. Setting: UK. Participants: Individuals from the British 1958 birth cohort.Measurements: Hearing thresholds at 1 and 4 kHz at age 44e45 years; m.1555A>G genotyping.Results: 19 of 7350 individuals successfully genotyped had the m.1555A>G mutation, giving a prevalence of 0.26% (95% CI 0.14% to 0.38%) or 1 in 385 (95% CI 1 in 714 to 1 in 263). There was no significant difference in hearing thresholds between those with and without the mutation. Single-nucleotide polymorphism analysis indicated that the mutation has arisen on a number of different mitochondrial haplogroups.Limitations: No data were collected on aminoglycoside exposure. For three subjects, hearing thresholds could not be predicted because information required for modelling was missing.Conclusions: In this cohort, hearing in those with m.1555A>G is not significantly different from the general population and appears to be preserved at least until 44e45 years of age. Unbiased ascertainment of mutation carriers provides no evidence that this mutation alone causes non-syndromic hearing impairment in the UK. The findings lend weight to arguments for genetic testing for this mutation prior to aminoglycoside administration, as hearing in susceptible individuals is expected to be preserved well into adult life. Since global use of aminoglycosides is likely to increase, development of a rapid test is a priority. ARTICLE SUMMARY Article focus-Individuals who have the m.1555A>G mutation are exquisitely sensitive to rapid-onset hearing loss after receiving aminoglycosides at normal therapeutic levels. -We sought to determine whether a cohort of mature individuals with the m.1555A>G mutation have hearing loss by their mid-40s because the mutation has been reported to cause lateronset less severe hearing loss in people who have never been exposed to aminoglycosides. We wished to determine whether genetic screening prior to aminoglycoside administration is justified. Key messages-This study demonstrates the prevalence of m.1555A>G to be 1 in 385 (95% CI 1 in 714 to 1 in 263) in the 1958 British birth cohort, confirming that this mutation occurs frequently in Caucasian populations. -The hearing of individuals with the m.1555A>G mutation is no different to that of the general population at age 44e45 years, in contrast to previous reports which suggested that hearing decreases with age in people with m.1555A>G; any such effect is not large and likely to be subject to previous ascertainment bias. -...

show abstract

Section: Discussionmentioning

confidence: 99%

Hearing in 44–45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study

Rahman

Ecob²,

Costello³

et al. 2012

BMJ Open

View full text Add to dashboard Cite

show abstract

“…Variants m.1555 A > G and m.1494 C > T in MT‐RNR1 alter the secondary structure of the human mitochondrial 12S rRNA such that it more closely resembles the homologous region of bacterial 16S rRNA and are the two most common variants associated with aminoglycoside‐induced hearing loss (AIHL) 2,3 . Hearing loss associated with aminoglycoside exposure can occur even after a single dose, may be bilateral, irreversible, and severe enough to necessitate cochlear implantation in rare cases 4–9 . The severity and onset of hearing loss in individuals with the associated pathogenic mitochondrial variants range from profound congenital deafness to mild to moderate late‐onset hearing loss.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Hearing loss associated with aminoglycoside exposure can occur even after a single dose, may be bilateral, irreversible, and severe enough to necessitate cochlear implantation in rare cases. [4][5][6][7][8][9] The severity and onset of hearing loss in individuals with the associated pathogenic mitochondrial variants range from profound congenital deafness to mild to moderate late-onset hearing loss.…”

Section: Introductionmentioning

confidence: 99%

Aminoglycoside induced ototoxicity risk in the cystic fibrosis population: The utility of large‐scale screening

Lopes

Vidal‐Folch²,

Lundquist³

et al. 2022

Pediatric Pulmonology

View full text Add to dashboard Cite

Background MT‐RNR1 variants are a well‐known cause of aminoglycoside‐induced hearing loss (AIHL). Individuals with cystic fibrosis (CF) routinely receive aminoglycosides and are at high risk of AIHL. However, genetic testing before treatment is not routinely performed due to perceived rarity of risk, and cost ineffectiveness with traditional technologies. Aim Assess the utility of large‐scale screening for AIHL risk in the CF population, using digital droplet polymerase chain reaction (ddPCR), a novel and scalable low‐cost molecular technique. Methods Using a clinically validated ddPCR assay, we performed retrospective testing on 122 and prospective testing on 32 individuals with CF for the two most common pathogenic variants associated with AIHL, MT‐RNR1 m.1555 A > G and m.1494 C > T. Our study screened the largest known cohort of pediatric cases of CF (94/154) for these specific alterations. Results We identified two individuals positive for MT‐RNR1 m.1555 A > G and no positives for m.1494 C > T. Of 32 prospective cases, 17 had aminoglycoside exposure. The positive case in our prospective group recently began inhaled tobramycin and denied hearing issues. The clinician adjusted to care for both the patient and sibling with CF (not included in cohort) who is presumed positive for m.1555 A > G due to the nature of mitochondrial inheritance. Conclusion Our findings demonstrate the utility of pretreatment screening in the cystic fibrosis population for AIHL risk using ddPCR, a scalable and robust testing methodology at a fraction of the cost as compared to other sequencing‐based methods. Therefore, the use of large‐scale screening for AIHL risk in the cystic fibrosis community should be re‐visited.

show abstract

“…Application of these factors may be useful for some groups of patients who require aminoglycoside treatment (e.g. gentamicin) and are at risk of developing hearing loss (Talaska et al, 2006;Bitner-Glindzicz et al, 2010;Prayle and Smyth, 2010). Regarding the protection/ regeneration of SGNs, administration of NFs, electrical stimulation and anti-oxidative treatment are the approaches most extensively studied (Pettingill et al, 2007;.…”

Section: Protection Via Administration Of Survival Factorsmentioning

confidence: 99%

Terapia celular dirigida contra la sordera: estudio de la capacidad de transdiferenciación de células madre mesenquimales humanas y de fibroblastos hacia células sensoriales del oído interno

Redondo¹

View full text Add to dashboard Cite

Aminoglycoside-induced deafness during treatment of acute leukaemia

Cited by 8 publications

References 6 publications

Hearing in 44–45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study

Hearing in 44–45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study

Aminoglycoside induced ototoxicity risk in the cystic fibrosis population: The utility of large‐scale screening

Terapia celular dirigida contra la sordera: estudio de la capacidad de transdiferenciación de células madre mesenquimales humanas y de fibroblastos hacia células sensoriales del oído interno

Contact Info

Product

Resources

About