EVALUATION OF HEARING IN PATIENTS WITH BETA THALASSEMIA MAJOR

This prospective study was conducted in Basrah Teaching Hospital to evaluate the hearing of β thalassemia major patients, and to find the association between desferoxamine (DFO) therapy and hearing loss (HL). Pure tone eudiometry (PTA) and tympanometry was done to determine hearing thresholds of (23) β thalassemia major patients and (50) non thalassemic subjects. All subjects were more than 4 year old to allow PTA to be done. The criteria of evaluation included a full otological history, drug history, otological examination, audiological evaluation using PTA and tympanometry. This study found that (6) out of (23) thalassemic patients and (6) out of (50) non thalassemic patients have hearing loss. From those thalassemic patients with HL, (5) patients have conductive hearing loss (CHL) and one have sensorineural hearing loss (SNHL), while the non thalassemic patients with HL all have CHL, also we found that (3) out of (5) thalassemic patients not on desferoxamine therapy have HL. In conclusion, β thalassaemia major has no significant statistical association with hearing problems, and there is no significant statistical association between desferoxamine therapy and hearing loss. Introduction he first branchial arch contributes Meckel's cartilage, which includes the malleus head and neck, incus body and short process, and anterior malleolar ligament. It also contributes the tensor tympani and the first three hillocks of His. The second branchial arch contributes Reichert's cartilage, which includes the manubrium of the malleus, the long process of the incus, and most of the stapes. It also contributes the last three Hillocks of His. the first branchial pouch contributes the Eustachian tube, mastoid air cells, and inner layer of the tympanic membrane. The first branchial cleft contributes the external auditory canal (EAC) and outer layer of the tympanic membrane. Bony labyrinth developed from otic capsule which encapsulates the otocyst that’s later on forms the membranous labyrinth. The external ear consists of pinna and external auditory canal which divided into cartilaginous and bony parts. the tympanic membrane separates the external from the middle ear by its three layers. The tympanic cavity is an air-containing cavity in the petrous part of the temporal bone contains the ossicular chain with its associated muscles, the aperture of the Eustachian tube, and vascular system. The cochlea is a coiled bony tube, snailshaped makes about 2.5 turns in the temporal bone. It is divided into three compartments; the scala tympani, scala vestibule, and scala media. T


Introduction
he first branchial arch contributes Meckel's cartilage, which includes the malleus head and neck, incus body and short process, and anterior malleolar ligament.It also contributes the tensor tympani and the first three hillocks of His.The second branchial arch contributes Reichert's cartilage, which includes the manubrium of the malleus, the long process of the incus, and most of the stapes.It also contributes the last three Hillocks of His. the first branchial pouch contributes the Eustachian tube, mastoid air cells, and inner layer of the tympanic membrane.The first branchial cleft contributes the external auditory canal (EAC) and outer layer of the tympanic membrane [1][2][3] .Bony labyrinth developed from otic capsule which encapsulates the otocyst that's later on forms the membranous labyrinth 4 .The external ear consists of pinna and external auditory canal which divided into cartilaginous and bony parts.the tympanic membrane separates the external from the middle ear by its three layers.The tympanic cavity is an air-containing cavity in the petrous part of the temporal bone contains the ossicular chain with its associated muscles, the aperture of the Eustachian tube, and vascular system [5][6][7] .The cochlea is a coiled bony tube, snailshaped makes about 2.5 turns in the temporal bone.It is divided into three compartments; the scala tympani, scala vestibule, and scala media.

T
The organ of Corti is a complex sense organ that contains inner and outer hair cells and supporting cells resting on the basilar membrane in the scala media [8][9][10] .Thalassaemia is the name given to a globin gene disorder that results in a diminished rate of synthesis of one or more of the globin chains and, consequently, a reduced rate of synthesis of the hemoglobin or hemoglobin's of which that chain constitutes a part.Thalassaemia may result from the deletion of a large part or all of a gene (as is usual in α thalassaemia) or from a small deletion or other mutation of a gene (as is usual in β thalassaemia) The thalassemias can be classified at different levels.Clinically, it is useful to divide them into three groups: the severe transfusion-dependent (major) varieties; the symptomless carrier states (minor); and a group of conditions of intermediate severity that fall under the loose heading "thalassemia intermedia" Those children with β thalasemia major usually become symptomatic from progressive hemolytic anemia with profound weakness and cardiac decompensation during the second 6 months of life if not treated.Transfusion therapy promotes general health and wellbeing and avoids the consequences of ineffective erythropoiesis.Iron overload is inevitable.Deferoxamine chelates iron and some other divalent cations, allowing their excretion in the urine and the stool if used appropriately [11][12][13] .Types of hearing loss; Conductive hearing loss (CHL): can be caused in external and or middle ear disease, Sensorineural hearing loss (SNHL): the sensory component of the cochlea, acoustic nerve, brain stem or cortex is damaged, Mixed hearing loss: the conduction of sound to the cochlea is impaired, as is the transmission through the cochlea to the cortex 14,15 .

Patients and methods
This is a prospective study conducted on (73) subjects attending the ENT department in Basrah Teaching Hospital, (23) patients have been previously diagnosed as β thalassaemia major were transferred from the thalassemic center in Basrah, while the remaining (50)subjects were non thalassemic selected randomly.All the patients were subjected to the same questionnaire, clinical and audiological examinations.Patients were more than 4 year of age (to allow for pure tone audiometry to be done) The questionnaire form included:

Results
Table I shows that most of the patients in this study are in the age group 1 (age 4-14 years), males are more than female, in regarding to the thalassemic patients.

Discussion
According to the results shown in tables III and IV, the hearing loss is more common in β thalassaemia major patients than in non thalassaemic patients, and the conductive loss is more common than sensorineural type in the former group.
In table V, the number of patients on desferoxamine therapy was more than patients not on desferoxamine, and the later group have more hearing loss than the former group.The data shown in table III were statistically analyzed using odds ratio to find the association between the disease and the suspected risk factor and chisquare test to find statistical significance or relation between two qualitative variables, the result was no statistical significance or relation between the β thalassaemia major and hearing loss (p>0.05).The data shown in table V were statistically analyzed using odds ratio to find the association between the disease *hearing loss* and the suspected risk factor *desferoxamine exposure*, the result found no association between the hearing loss and desferoxamine exposure.
The findings in our study shared with the following studies: Ambrosetti et al (2000) have been studied 57 β thalassaemia major patients over 3 years, he found that there was no significant difference between thalassaemic and non thalassaemic patient of same age; desferoxamine treatment seems to be non ototoxic when employed at the present dosage 16 .Mojabi (2001) have been studied 65 thalassemic patients and 65 non thalassemic, and found that the hearing loss in thalassemic patients was 2.2 times higher than the control group, the type of hearing loss was totally conductive 17 .Bibi shahin shamsian et al (2008) have been studied 67 patients over 5 years, he found that there were no significant difference between SNHL and non SNHL in patient age, sex, serum ferritine level, it seems that SNHL is not directly related to serum ferritin level or desferoxamine dosage and other factors 18 .In contrast, Kontzoglou et al (1996)  studied 88 patients over 6 years, this study confirms that desferoxamine induced auditory neurotoxicity and the necessity of periodical audiological control of β thalassaemia major patient 19 .Albera et al had obtained the results of audiometric screening of 153 children aged 5-18 years affected by β thalassemia and treated with regular transfusion and desferal therapy, they found that 38% of the patients having SNHL at higher frequencies, and CHL was not more than in patients with outthalassemia 20 .Nezameddin Berjis et al (2003) have been evaluated 190 β thalassemia major patients for otorhinolaryngological manifestations, they found that 3.5% have clinical hearing loss and 50% having SNHL 21 .The reason for the difference between this study and studies done by (Umbrosetti, Mojabi, and Shamsian) and other studies (Kontzoglou, Albera, Nezamaddin), is probably due to the higher dose and longer duration of treatment with desferoxamine in the latter studies.

Conclusion and recommendation
The β thalassaemia major has no significant statistical association with hearing problems, and there is no significant statistical association between desferoxamine therapy and hearing loss.A larger study is required to clarify the controversy between different studies about this problems, until then hearing evaluation of β thalassaemia major patients taking desferoxamine and those not taking desferoxamine by audiometry is recommended because of the importance of this complication if it happens and the subsequent disabilities.