In Vivo Base Editing for Neonatal Inborn Errors of Metabolism: Clinical Progress, N-of-1 Therapy, and the Ethics of Bespoke Genetic Medicine.

Hearing impairments do not mostly display as hearing damage, and somewhen they appear in the shape of abnormal sound sensitivity, which is called hyperacusis. In this condition, tolerable noises for the general public will be highly loud and intolerable for sufferers. Hyperacusis makes several difficulties in standards of daily living for their victims and damages to their educational, occupational and social positions depending on the patient's age. Hyperacusis sufferers typically have negative emotional relation with their surrounding noise. Their responses to generating sources can be annoyance, impatience, increased heart rate, sweating, nervousness, and etc. They may have central auditory processing disorders (CAPD), since they are more attentive and aware of the circumstantial noises compared to people without CAPD, who can easily filter out background noise (-). Researchers have shown that its incidence is 7% to 23% in the general public (,), and in patients with the chief complaint of tinnitus, its occurrence is 40% (). Approximately 90% of the patients combined hyperacusis report tinnitus, suggesting an association among them (). The underlying mechanisms of hyperacusis and tinnitus are unknown. They can happen without hearing loss and are associated with increased sound-induced arousal in the brainstem and the auditory cortex (). Another possibility is that they may result from increased neural coherence and reorganization of the tonotopic map in the auditory brain (). The brain activity in patients with hyperacusis are enlarged in the frontal and occipital hemispheres. Indeed, their extra-auditory cortices are cooperative for the sound feedback (). While, the right superior temporal gyrus of the auditory brain is principal in normal people (). Hyperacusis can occur due to various neurological and structural causes, such as chronic fatigue syndrome (), head trauma, facial paralysis, depression, anxiety, post-traumatic stress disorder, hearing loss, autism (), metabolic conditions, infections and genetic diseases (). Hyperacusis can distract the health aspects of the sufferers, which consist of emotional comfort, hearing, communication, sleep, and attention (,). The routine measures of auditory evaluations are not suitable for hyperacusis (,,). The appropriate methods including the LDL and hyperacusis questionnaires, which are commonly recommended. They are the most reliable approaches to study of its symptoms (-). Also, two Persian version of the questionnaires {the Inventory of Hyperacusis Symptoms (2) and HQ (3)} show no significant correlation with the pure tone audiometry (). They estimate three parts of attentional, social, emotional significance and also have high validity/reliability for routine procedure of diagnosing and following up the rehabilitation (,). The essential treatments of hyperacusis are cognitive behavioral therapy and sound treatment, which emphasis on responses, emotions and thoughts. They are also two main portion of tinnitus retraining therapy.