Sickle cell disease (SCD) is an autosomal recessive genetic hemolytic disorder affecting red blood cells.1,2 The most common of all the genetic hemolytic disorders, it affects approximately 100,000 Americans and occurs roughly in one of every 365 and one of every 16,300 black or African-American and Hispanic-American births, respectively.3 The inherited hemolytic disorder results from an amino acid substitution (i.e., valine for glutamic) on the sixth position of the hemoglobin beta chain. In normal healthy individuals, hemoglobin is genetically coded HbAA. In those with SCD, a mutated gene (HbS) or a copy of HbS plus another beta-globin variant replace the normal genes that code for hemoglobin. In addition to the homozygotic HbSS, five major sickle genotypes have been identified: HbSβ0, HbSβ+, HbSC, HbSD, and HbSE.1,2
Interestingly, SCD has a genetic advantage in that it protects against malaria. Unfortunately, those with SCD experience significant morbidity and mortality. The characteristic sickle shaped red blood cells associated with SCD, compared with the normal disc shaped red blood cells, have numerous pathophysiologic disadvantages. These include hemolytic anemia and vaso-occlusion. The sequela of anemia and vaso-occlusion includes local hypoxia, increased erythrocyte sickling, and spread of occlusion to adjacent tissue. This can lead to “crisis” episodes where the individual with SCD suffers from intense pain and organ malfunction.1,2
SCD AND HEARING LOSS
The hearing system is not immune to SCD. Histopathological and degenerative changes have been observed in the temporal bone and organ of Corti in those with SCD.4 These findings are consistent with hypoxia and would be expected considering the microvasculature of the cochlea. Functional changes in the hearing status of those with SCD are also consistent with the histopathology. Hearing loss in those with SCD includes sensory, conductive, and central etiologies.5,6 The prevalence of sensorineural hearing loss among those with SCD is higher than the general population. Estimates of prevalence range from 11 to 66 percent in adults with SCD.4
In the United States, the prevalence of hearing loss among children with SCD ranges from 12 percent to 26 percent.8,9 This is well above the general prevalence of hearing loss in pediatric cohorts in Canada and the United States (7.7% to 15.2%, respectively).10,11 In addition, the degree of hearing loss rises with increasing age.12 Compared with adults, children with SCD have a lower prevalence of sensory hearing loss.13 These observations may suggest that sensory hearing loss in childhood is progressively slow and insidious in nature, which is supported by our previous research. We found that normal hearing children with SCD present with sub-clinical cochlear damage in the form of abnormal otoacoustic emissions relative to age- and sex-matched normal hearing children.14-17 Also, normal hearing children and adolescents with SCD have abnormal acoustic reflexes and auditory brainstem responses.18 Individuals with SCD, who have been identified with sensorineural hearing loss in childhood, as a rule, passed their newborn hearing screening consistent with an acquired hearing loss.19
FOCUS ON CHILDREN
Recently, we examined a large medical and research database from the Children's Hospital of Philadelphia to further investigate the emergence and prevalence of hearing loss in children with homozygous SCD.20 Normal hearing was defined as hearing thresholds ≤ 15 dB HL for pure tone air conduction audiometry and ≤ 20 dB HL for sound-field testing. Children were identified as having hearing loss if a hearing threshold at any frequency was > 15 dB HL for pure tone air conduction audiometry or > 20 dB HL minimal response level for sound-field testing. The degree of hearing loss was categorically defined by degree of threshold or minimal response level elevation as slight (16-25 dB HL), mild (26-30 dB HL), moderate (31-50 dB HL), severe (51-70 dB HL), or profound (≥ 71 dB HL). Hearing loss etiology was categorized as conductive, sensorineural, mixed, or unspecified. A three-frequency pure tone average (PTA; 500, 1000, and 2000 Hz) was also calculated when available data permitted.
From the initial database of over 95,000 patients, 128 children were identified with homozygous SCD who had at least one audiogram. Ear specific information was obtained on 255 of the total 256 ears. The prevalence of hearing loss in this group of children ranged from 29 percent to 51 percent depending on the calculation method employed. When defining hearing loss as the presence of one elevated threshold, prevalence was as high as 51 percent. The ear-specific prevalence was 43 percent when defining hearing loss the same way by elevated audiometric threshold. Using the three-frequency PTA, prevalence estimates were lower at 34 percent and the ear specific prevalence was 29 percent. Regardless of the calculation method, the prevalence of hearing loss in children with homozygous SCD is high compared to normal children.
Several trends were also identified in the data. Bilateral hearing loss was found to be more common among children compared to unilateral deficits. The degree of hearing loss ranged widely among children with homozygous SCD. The majority of losses were in the slight degree category, with a positive skewness in distribution. No visible differences were found between the right and left ears with respect to normal hearing and degree of hearing loss. Conductive hearing loss was found to be more prevalent than sensorineural loss. The first audiometric evaluation of children with homozygous SCD and sensorineural hearing loss occurred at a mean age of 8.9 years. The sensorineural hearing loss diagnosis followed shortly after at a mean age of 9.6 years. Children identified with conductive hearing loss had a slightly lower age of first audiometric evaluation of 6.9 years. Figure 1 illustrates the percentage of normal hearing and hearing loss as a function of degree and ear. Figure 2 shows the prevalence of hearing loss as a function of etiology and laterality.
Multiple developing comorbidities typically accompany children with SCD as they transition to adult medical care.21 Considering the high prevalence and emergence of hearing loss in children with homozygous SCD, hearing loss must be viewed as one of those complications. Understanding this leads one to advocate for audiometric evaluation as part of the ongoing assessment of children with SCD. Unfortunately, current management practice for children with SCD does not include hearing assessment.22 Diagnosed and treated hearing loss minimizes the impact on language, speech, communication, cognition, and academic performance. Audiologists should, therefore, advocate for early and ongoing hearing assessments of children with SCD as part of their ongoing hearing care.
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