Keywords otorhinolaryngology - pediatrics - mucopolysaccharidosis - audiology
Palavras-chave otolaringologia - pediatria - mucopolissacaridoses - audiologia
Introduction
Mucopolysaccharidoses (MPS) represent a group of diseases characterized by the deficit
of lysosomal enzymes lowering the glycosaminoglycans (GAGS), which are carbohydrate
polymers and proteins. They are a part of a group of hereditary metabolic diseases
known as inborn errors of metabolism. MPS are rare diseases separately, but jointly
they have an estimated incidence of 1:10000 to 1:25000[1 ].
There are seven known types of mucopolysaccharidosis based on both clinical characteristics
and the deficient enzyme ([Table 1 ]). All of them present an autosomal recessive inheritance, except for the type II
(Hunter's syndrome) presenting an X- associated inheritance. Accumulating these metabolites
causes several alterations, and these children are generally born without these alterations
and develop them progressively[2 ].
Table 1.
Subtypes of MPS and the main otorhinolaryngological alterations
Subtype of MPS
Main otorhinolaryngological alterations
MPS I (Hurler, Scheie, Hurler-Scheie)
Sleep apnea, IVAS, otitis media, sensorineural hearing loss
MPS II (Hunter)
Adenoamydgale hypertrophy, otitis media, sensorineural hearing loss
MPS III (Sanfilippo) TYPE A,B,C and D
Otitis media, adenoamygdale hypertrophy
MPS IV (Morquio) TYPE A and B
Otitis media, adenoamygdale hypertrophy
MPS VI (Maroteaux-Lamy)
Progressive and diffuse narrowing of airways, otitis media, adenoamygdale hypertrophy
MPS VII (Sly)
Similar to Hurler's syndrome
MPS IX (Natowicz)
Not described
The diagnosis is made by the GAG standard in urine and confirmed by the analysis of
lysosomal enzymes in blood, leukocytes or, in addition to a genetic study. In suspected
cases, amniocentesis and biopsy of chorionic vilosities allow for the prenatal diagnosis[3 ].
Clinical presentation can be wide-ranging, and the most common manifestations are:
skeletal and cardiac alterations, mental retardation, organomegaly and characteristic
facies[3 ].
The otorhinolaryngologic alterations of these patients can be divided into three groups:
otologic alterations, adenotonsillar hypertrophy and airway alterations.
Adenotonsillar hypertrophy is sensibly universal by reason of the deposit of glycosaminoglycans,
therefore, an indication of adenoamygdalectomy is frequently noticed on these patients.
This type of deposit can as well be seen on the pharynx walls and, when in association
with macroglossia and mandible abnormalities (occasionally they are seen on MPS cases),
there is the risk of progressive obstruction of upper airways and sleep apnea. Additionally,
infections recurring from the upper respiratory tract can also cause tonsillar diseases
associated with this disease. With respect to managing the obstruction of the upper
airways, firstly adenoamygdalectomy is performed and, in most of the cases, it is
the only necessary treatment. Occasionally, in extreme cases, there is a need for
tracheotomy[2 ].
In association with adenotonsillar hypertrophy, there can still be a deposit of glycosaminoglycans
on both pharynx and larynx walls, especially in arytenoid cartilages and aryepiglottic
membranes. In extreme cases, due to the accumulation of mucopolysaccharides, there
is a prolapse of laryngeal wall, provoking stridor and a severe obstruction of the
airways. Besides, there is a possibility of deposit on tracheal walls with a subsequent
narrowing of lumen[2 ].
In the present study, we shall emphasize the otologic alterations. The most common
alterations are: otitis media with effusion (OME), which can lead to both conductive
hearing and sensorineural alterations[4 ].
The objective of this study is o evaluate a number of patients with mucopolysaccharidosis
at Pequeno Principe Hospital, emphasizing their audiologic alterations and establish
a permanent evaluation protocol for these patients.
Method
The present work is characterized as a backward-looking study of audiologic evaluation
by using records of 18 patients diagnosed with mucopolysaccharidosis and attended
at Pequeno Principe Hospital between January 2005 and November 2010.
The evaluation of the hearing loss was performed by analyzing the data achieved by
a pure-tone threshold audiometry, impedance audiometry, AEP (Brainstem Auditory Evoked
Potential) and TOE (transient otoacoustic emissions), and the degree of hearing loss
is analyzed in accordance with the International Bureau for Audiophonology's classification[5 ].
The collection of information was performed by filling out a form based on each patient's
records ([Annex 1 ]).
Annex 1.
Form - MPS.
The research project was evaluated and approved by the Ethical and Research Committee
of Human Beings of Pequeno Principe Hospital (registration N° 0822-10).
Patients – inclusion criteria
The criteria to include patients in this study are as follows:
To present a diagnosis of mucopolysaccharidosis;
To present an audiologic evaluation and description of an otorhinolaryngologic physical
examination in the record;
Absence of erasures and/or unintelligible writing;
Selecting patients
The selection of patients for this study complied with the following plan:
To acquire at Pequeno Principe Hospital's SAME a list of the patients served and diagnosed
with mucopolysaccharidosis in the period between January 2005 and November 2010;
Patients' conformity with the inclusion criteria.
Outlining the study
After selecting the records, their data were analyzed by filling out a specific form
([Annex 1 ]).
The described audiologic alterations were divided into conductive, sensorineural and
mixed. The degree of hearing loss was analyzed in accordance with International Bureau
for Audiophonology's classification[5 ].
The therapeutics established for each specific situation was equally analyzed.
Results
On the whole, the records of 18 patients diagnosed with mucopolysaccharidosis served
in the period between January 2005 and November 2010 were evaluated.
From this total, 7 records were selected in accordance with the inclusion criteria
described in the method. Same were numbered from 1 to 7.
The group's average age was 11 years; 5 patients were male and 2 were female ([Table 2 ]).
Table 2.
List of patients in accordance with age, sex, MPS type, audiologic examination, hearing
loss and procedures performed.
Patient
Age
Sex
MPS type
Exams
Hearing loss
Procedure performed
1
19
F
I
Audio/AEP
SN
None
2
16
F
VI
Audio/Imp
Slight mixed
VT
3
13
M
I
Audio/AEP
Normal
A/Ad
4
11
M
II
Audio/Imp
Moderate mixed
A/Ad/VT
5
10
M
VI
Audio/Imp
Slight conductive
Ad/VT
6
07
M
II
Imp
Suggestive conductive
A/Ad/VT
7
01
M
II
Imp
Suggestive conductive
Ad/VT
Imp = impedance audiometry SN = sensorineural VT = ventilation tube A = amygdalectomy
Ad = adenoidectomy
Two patients had a type 1-MPS diagnosis, three patients had the type II and two patients
had the type IV ([Table 2 ]).
From the seven patients, five performed either audiometry and impedance audiometry
examinations or audiometry and AEP, whilst two performed only impedance audiometry
([Table 2 ]).
With respect to the type of hearing loss, 42.8% (three patients) had exclusively conductive
type, 28.5% (two patients) had the mixed type, 14.3% (one patient) had exclusively
sensorineural type, and in 14.3% (one patient) the examination was normal ([Table 2 ]).
The group, one patient was submitted to adenoamygdalectomy procedure, one patient
was submitted only to ventilation tubes, two patients were submitted to adenoidectomy
with ventilation tubes, two patients were submitted to adenoamygdalectomy and ventilation
tubes, and one patient was not submitted to any otorhinolaryngological surgical procedure
([Table 2 ]).
Discussion
MPS otorhinolaryngologic manifestations can be divided into three groups: otologic
problems, adenotonsillar hypertrophy and airways disorders. Minor degrees attacks,
such as otitis media with effusion, are nearly universal in this group of patients[2 ].
Owing to the deposit of mucopolysaccharides on rhinopharynx, hearing tubes and middle
ear, these patients presented an elevated risk of developing otitis media with effusion
and recurring episodes of acute otitis media. Whenever indicated, symptomatic treatments
must be put into practice as a placement of ventilation tubes and hearing apparatus
when indicated.
It is unclear whether the sensorineural element has a congenital basis or it is secondarily
acquired to the deposit of glycosaminoglycans partially lowered in the cochlear duct,
stria vascularis in the cochlear nerve or even in the central nervous system. This type of sensorineural
loss is particularly noticed in patients with types I and II-MPS[4 ]
[7 ]. Besides, the deposits in the middle ear can explain the inability that some patients
have to recover the difference between the airways and the bone conductions in the
audiometry after performing tympanotomy[4 ]. Unluckily, the hearing loss is frequently noticed at the moment of diagnosis and,
while the conductive hearing loss is unlikely to improve, amplification is usually
required in cases of permanent sensorineural loss[4 ]
[7 ].
In a backward-looking study (n = 9) with the intention of evaluating the otorhinolaryngologic
alterations found in children with a confirmed diagnosis of mucopolysaccharidosis,
it has been noticed the 100%-prevalence of recurring otitis media in the evaluated
group. Additionally, all the patients in the series were submitted to tympanotomy
at least once and 78% of them were submitted to multiple tympanotomy with the placement
of ventilation tubes. Hearing loss was demonstrated by audiometry in 78% of patients.
Of this group, 71% had mixed hearing loss, 14% had only sensorial hearing loss and
14% had only a conductive one[4 ].
Further to the management of the symptoms and individual manifestations, efforts have
been made to control the pathologic processes as a whole, in an attempt to block or
at least adjourn the evolution of the disease. The transplantation of osseous medulla
has been investigated since the 1980's and has been frequently used in MPS children
under 2 years of age or in those patients with slight forms of MPS II, VI or VII[8 ]. Literary data shows a reduction in hepatosplenomegaly, an improvement in airway
obstruction, a reduction in the intracranial hypertension and a reduction of the glycosaminoglycan
deposits in the cephalorachidian liquid, liver and skin of children submitted to the
transplantation of bone marrow, probably due to restoring the ability of the organism
in lowering substrates accumulated on cellular level[9 ]. Besides, comparative studies have suggested that the transplantation would result
in improving both the hearing ability and the voice in comparison with groups without
a treatment[10 ]. More recently, therapies of enzymatic replacement have been developed and used
in the treatment of the different types of mucopolysaccharidosis. Although studies
demonstrate the promising effect of replacement, there is no random clinical essay
demonstrating their actual efficiency yet[4 ].
Conclusion
Mucopolysaccharidosis patients require a permanent care and a follow-up with multidisciplinary
professionals. In this context, the pediatric otorhinolaryngologist plays an important
role when performing the otologic and audiologic evaluation and managing the airways,
since almost all the patients evaluated presented some kind of hearing loss and an
indication of otorhinolaryngologic procedure. The clinical suspicion, the early recognition
of lesions, as well as the rehabilitation are essential to achieve better results,
minimize the sequels and provide a better quality of life to the patients and their
relatives. The pattern determined in our service was at least an initial consultation
when there is a suspicion and/or diagnosis of MPS and sequential consultations that
were at least twice a year or more frequent, if necessary.
