RESUMO
OBJECTIVE: Aminoglycoside ototoxicity remains a major problem in developing countries and accounts for 3 percent to 30 percent of hearing loss. This high prevalence rate may be related to genetic susceptibility from mitochondrial mutations in the 12S rRNA gene, comorbidity factors, or unregulated use of the medication. This study investigates the risk factors and prevalence of mtDNA mutations in serum from rural Nicaragua children with aminoglycoside-related hearing loss. STUDY DESIGN: Cross sectional study. SUBJECTS: Deaf children from rural Nicaragua. METHODS: Mitochondrial DNA isolated from serum collected from 31 deaf children with childhood or in utero exposure to gentamicin was amplified, sequenced, and analyzed for mutations in the 12S rRNA gene. RESULTS: No known pathologic mutations of the 12S rRNA gene were identified in this subpopulation of deaf children. In addition, patients with gentamicin exposure were often likely to have other comorbidity factors. CONCLUSION: These results suggest that genetic susceptibility is not a major factor in the high rate of gentamicin ototoxicity in this population sample. The high prevalence of gentamicin ototoxicty in this population is presumed to be due to unrestricted access to the drug.
Assuntos
Aminoglicosídeos/toxicidade , DNA Mitocondrial/efeitos dos fármacos , Predisposição Genética para Doença/genética , Perda Auditiva/induzido quimicamente , Perda Auditiva/genética , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Dopaminérgicos/toxicidade , Feminino , Gentamicinas/toxicidade , Humanos , Masculino , Mutação , Nicarágua , RNA Ribossômico/genética , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE/HYPOTHESIS: The prevalence and causes of pediatric hearing loss (HL) in the developing world are largely unknown. Infectious sequelae, ototoxic medications, and genetic causes may play a larger role in developing countries. In addition, the significance of GJB2 mutation gene in poorly developed areas remains unclear. The intent of this study is to investigate the prevalence and etiology of HL in children living in a remote, impoverished region of northern Nicaragua. STUDY DESIGN: Cross-sectional study. METHODS: Clinical data from two sources were analyzed: data from screening examinations performed in rural schools in the Department of Jinotega, Nicaragua (group A) and pediatric HL patients seen at the Otolaryngology and Audiology Clinic in Jinotega, Nicaragua (group B). Patients with congenital HL were offered a genetic test for GJB2 mutations. Comparisons were made using parametric (analysis of variance) and nonparametric (Kruskal-Wallis) tests. RESULTS: School-based screening examinations (group A) revealed a high prevalence of significant HL (>30 dB) of 18%. The majority of these children had normal otoscopic examinations (58%). A family history of HL was seen in 24% of children who failed screening exams. Positive family history was more common in patients with HL (P < .01) and in specific schools (P < .05). Clinic-based evaluations (group B) reveal a population with predominantly severe-profound HL. Physical dysmorphism was common, yet identifiable syndromic HL was rare. Although familial HL was common (33%), there were no pathologic GJB2 mutations. Other common risk factors in this population were maternal infection during pregnancy, neonatal distress, low birth weight or prematurity, and gentamicin exposure. CONCLUSIONS: HL in this rural, third world environment is more prevalent, and the etiologies responsible in this study group are different from those encountered in industrialized nations. Poor perinatal health care, infectious causes, gentamicin exposure, and hereditary HL are potentially preventable causes that play a major role in this population.