International Journal of Pediatric Otorhinolaryngology

58 (2001) 127138
Disordered breathing during sleep in patients with
mucopolysaccharidoses
S.E.J. Leighton
a,
*, B. Papsin
a
, A. Vellodi
b
, R. Dinwiddie
c
, R. Lane
c
a
Department of Otolaryngology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK
b
Metabolic Unit, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK
c
Portex Anaesthesia Intensi6e Therapy & Respiratory Medicine Unit, Institute of Child Health, London WC1N 1EH, UK
Received 20 September 2000; received in revised form 2 January 2001; accepted 2 January 2001
Abstract
Objecti6e: Obstructive sleep apnoea (OSA) has been reported as a feature of children with mucopolysaccharidoses
(MPS). However, the incidence and severity of OSA with respect to disease type is poorly dened. The aim of the
present study was to measure objectively the degree of OSA in a group of children with a range of MPS syndromes.
Methods: In a cross-sectional study, cardiopulmonary sleep studies were performed during unsedated sleep in 26
children with MPS over a period of 2 years. Scores of OSA severity based upon clinical history and upon objective
sleep study data were made in each case and compared. Results: OSA was present in 24/26 patients, and ranged in
severity from mild to severe. OSA was most marked in MPS type IH (Hurler syndrome) followed by types IHS
(HurlerScheie syndrome) and II (Hunter syndrome). Frequent arousals and poor sleep quality, not suspected
clinically, were noted in several patients. There was agreement between the clinical and objective scoring systems in
only 17/26 patients (65%) with clinical history scores tending to underestimate the most severe cases (5/26 cases) and
overestimate the severity in the mild cases (4/26 cases). Conclusions: Obstructive respiratory problems are frequent in
MPS patients and there are differences in severity of OSA between the different MPS types. Assessments of the
severity of OSA based upon clinical history alone are inadequate. Our results suggest that objective sleep studies are
necessary to evaluate these cases, to monitor clinical outcome and to assess the effects of therapeutic intervention.
Prospective studies in larger numbers of patients are needed to validate these observations. 2001 Elsevier Science
Ireland Ltd. All rights reserved.
Keywords: Sleep apnoea; Mucopolysaccharidoses; Sleep; Child
www.elsevier.com/locate/ijporl
1. Introduction
The mucopolysaccharidoses (MPS) are a group
of genetic disorders, classied biochemically by
defective lysosomal catabolism of glycosaminogly-
cans [1] and leading to an accumulation of specic
glycosaminoglycans (Table 1). Respiratory in-
* Corresponding author. Tel.: +44-207-813-8220; fax: +
44-207-829-8644.
E-mail address: kate.king@virgin.net (S.E.J. Leighton).
0165-5876/01/$ - see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0165-5876(01)00417-7
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 128
volvement is common in affected individuals, and
is progressive, with the precise timing, nature and
severity related to the underlying disorder [2].
Affected individuals classically have a number of
anatomical features predisposing them to airway
compromise [2,3]. In the upper airway these in-
clude abnormal cervical vertebrae, a short neck, a
high epiglottis, a deep cervical fossa narrowing
the nasopharynx and a hypoplastic mandible with
short rami [3]. In the lower airway there is a small
thoracic cage, frequently complicated by
kyphoscoliosis. In addition, glycosaminoglycans
are progressively deposited in the tissues sur-
rounding the upper respiratory tract in the
nasopharynx, oropharynx, hypopharynx and lar-
ynx, and this may contribute to upper airway
obstruction (UAO) [2]. Tonsillar [4] and ade-
noidal [5] hypertrophy and macroglossia [3,6] are
recognised features and there is progressive distal
spread of airway obstruction as tracheobronchial
cartilage is affected and tracheobronchial narrow-
ing and tracheobronchomalacia ensue [7,8].
Furthermore, hepatosplenomegaly may limit di-
aphragmatic excursion, and interstitial pulmonary
deposition of mucopolysaccharides may result in
a diffusion defect. Thickened and copious secre-
tions throughout the upper and lower respiratory
tracts are also commonly found and there is a
tendency to frequent upper and lower respiratory
tract infections [9,10]. Chronic hypoxaemia may
result in pulmonary hypertension, and cor pul-
monale [2]; cardiorespiratory failure is the usual
cause of death. Breathing may only be signi-
cantly obstructed when affected individuals are
sleeping [2]. During active (rapid eye movement,
REM) sleep, the upper airway is vulnerable to
collapse, as there is a physiological decrease in
tone of the supporting muscles and consequent
increase in resistance to airow [11]. When this is
superimposed on an already narrow airway, ob-
struction may develop and breathing may become
impaired, resulting in obstructive sleep apnoea
(OSA).
The aim of the present study was to evaluate
and document the breathing patterns during sleep
of untreated children with MPS. It was antici-
pated that the availability of baseline data for
breathing patterns in these children would facili-
tate the diagnosis and quantication of the sever-
ity of UAO. Furthermore objective scoring
systems will assist in the evaluation of the effect
on the airway of therapeutic interventions such as
adenotonsillectomy, tracheostomy, nasal continu-
ous positive airways pressure (n-CPAP) or bone
marrow transplantation.
Our criteria for assessment of respiration dur-
ing sleep based on clinical history and observation
are also reported, and the relationship of the
results of such clinical assessments with those of
objective sleep study results examined. If good
correlation can be achieved, it may reduce the
frequency of need for serial sleep studies in the
management of children with MPS and obstruc-
tive airway disorders.
2. Patients and methods
Twenty-six patients with MPS were studied
over a 2 year period from March 1994 to Febru-
ary 1996. The study group comprised 21 boys and
5 girls aged 0.318.4 years (mean 5). All were
untreated and had diagnoses conrmed by leuko-
cytic enzyme assay [1]. Individual patients details
are summarised in Table 2.
Whilst patients for sleep study were selected on
the basis of clinical need, those studied formed a
relatively balanced cross-section of the total popu-
lation of 75 MPS patients registered at our insti-
Table 1
Classication of the MPS with associated enzyme decits
Syndrome Decient enzyme Type
a-L-Iduronidase MPS IH Hurler
MPS IS Scheie a-L-Iduronidase
a-L-Iduronidase MPS IHS HurlerScheie
MPS II Hunter Iduronate sulfatase
Sanllipo A Heparan N-sulfatase MPS IIIA
MPS IIIB a-N-Acetylglucosaminid Sanllipo B
ase
Sanllipo C MPS IIIC N-Acetyltransferase
MPS IVA Galactose 6-sulfatase Morquio A
b-Galactosidase MPS IVB Morquio B
Maroteaux-Lamy MPS VI N-Acetylgalactosamine
4-sulfatase
Sly MPS VII b-Glucuronidase
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 129
Table 2
Individual patient details giving age at time of study, sex and
MPS diagnosis
a
No. Sex Age (yr) Diagnosis
M 1 MPS-IH Hurler 1.1
2 2.6 F MPS-IH Hurler
M 3 MPS-IH Hurler 0.3
M 5.8 MPS-IH Hurler 4
M 5 MPS-IH Hurler 1.1
M 3.3 MPS-IH Hurler 6
3.4 7 F MPS-IH Hurler
F 1.1 MPS-IH Hurler 8
6.8 9 M MPS-IHS HurlerScheie
M 10 MPS-IHS HurlerScheie 13.8
M 3.0 MPS-II Hunter 11
M 12 MPS-II Hunter 0.7
M 3.5 MPS-II Hunter 13
17.4 14 M MPS-II Hunter
M 2.1 MPS-II Hunter 15
4.4 16 M MPS-II Hunter
M 17 MPS-IIIA Sanllipo A 3.1
M 2.9 MPS-IIIA Sanllipo A 18
M 19 MPS-IIIA Sanllipo A 1.8
M 3.8 MPS-IIIB Sanllipo B 20
9.1 21 M MPS-IV Morquio
M 9.8 MPS-IV Morquio 22
18.4 23 F MPS-IV Morquio
24 4.3 M MPS-IV Morquio
F 2.2 MPS-VI 25
Maroteaux-Lamy
M 26 MPS-VI 3.6
Maroteaux-Lamy
21 Male Mean MPS-I (10) 5.0
S.D. 5 Female 4.9 MPS-II (6)
MPS-III (4)
MPS-IV (4)
MPS-VI (2)
a
Patients 2, 3 and 4 were siblings.
respiratory problems, particularly sleep-related
breathing anomalies. With the aid of a sleep diary
completed by the parents for the week preceding
the sleep study, the areas covered included normal
sleep patterns, normal routine at home, normal
bed-times and bed-time rituals, wakings during
sleep, extent of disturbed or restless sleep, sweat-
ing, snoring, cessation of breathing, cyanosis,
difculty in initiating or maintaining sleep,
difculties in waking from sleep, daytime perfor-
mance and mood. Based upon these reported
symptoms, sleep-respiratory problems were
graded as none, mild, moderate or severe accord-
ing to the criteria listed in Table 3 [12].
Sleep studies were performed overnight during
natural, unsedated sleep in a ward environment.
Studies were of a maximum of 10 h duration and
commenced once the child settled in bed and was
observed to fall asleep. The studies comprised
overnight monitoring with continuous and simul-
taneous recording of the following variables: (1)
rib cage and abdominal respiratory movements
(strain gauges); (2) arterial oxygen saturation
(SaO
2
) and pulse rate (PR) by pulse oximetry; (3)
heart rate (HR) from a single-lead electrocardio-
gram (ECG); (4) video and sound. The CARDAS
(Oxford, UK) computer-based sleep system was
used to record and analyse data. Direct clinical
(video) observation of the sleep study was per-
formed by an experienced observer and sleep stag-
ing was performed according to behavioural
criteria [13]. Behavioural quiet sleep (QS), which
Table 3
Criteria for assessment of respiratory problems based on clini-
cal history
Severity Symptoms and signs
9Mouth breathing Mild
9Slightly increased respiratory efforts
9Snoring
Moderate 9Noticeably increased breathing difculties
9Minor sleep disturbance
9Snoring
Severe 9Markedly increased breathing difculties
9Very disrupted sleep
9Cyanosis
9Snoring
tution during the study period; they comprised 27
MPS IH (36%), 11 MPS II (15%), 14 MPS III
(19%), 10 MPS IV (13%) and 13 MPS VI (17%).
2.1. Sleep studies
Patients were admitted for overnight cardio-res-
piratory sleep studies to assess the baseline
breathing pattern and to evaluate and quantify
the severity of UAO during sleep. Prior to the
sleep study a detailed clinical history was taken by
an experienced clinician with emphasis on any
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 130
corresponds approximately to non-REM deep
sleep was identied as periods during which there
were no facial movements, only occasional
startles, infrequent movements of the extremities,
a relatively constant HR and a regular breathing
pattern. Conversely, behavioural active sleep
(AS), which approximates to REM sleep, was
dened as periods where there were more frequent
movements of the body and extremities, facial
grimaces, REMs, variable HR and an irregular
pattern of breathing.
Individual sleep studies were analysed using an
interactive computer program (CARDAS). Peri-
ods of wakefulness or artefactual signals were
identied by inspection of the raw data signals
with reference to the video and sound recording
and observational notes, and were then excluded
from further analysis. The total time in bed (TIB),
total sleep time (TST; i.e. excluding all periods
classied as awake of \1 min duration, before,
during or after sleep), QS% and AS% were
derived for each study. Time in bed was used to
normalise the data in terms of a sleep efciency
score (TST/TIB100% [14]) since limitations of
the ward environment meant that in the youngest
children the length of the study would otherwise
have failed to include their total sleep period.
Respiratory patterns were analysed manually in
B5-min epochs to allow visualisation of individ-
ual breaths and to facilitate the identication of
both central and obstructive respiratory episodes.
Central pauses were dened as periods in which
there was a cessation of respiratory movements in
both rib cage and abdominal signals. The severity
of the central pause was assessed by the impact on
SaO
2
(see below). Obstructive apnoeas/hypop-
noeas were identied using a combination of
video/sound and polygraphic data. Inspection of
the polygraphic data was used to dene the rela-
tionship between rib cage and abdominal move-
ments, which ranged between being completely
synchronous and being completely paradoxical,
and the extent of the change in SaO
2
caused by
the obstructive episode.
The severity of respiratory anomalies was quan-
titatively assessed by detailed analysis of the SaO
2
signal. SaO
2
and PR data were sampled at 1 Hz.
The mean and standard deviation (S.D.) values
for the SaO
2
signal were calculated for the whole
study and for the periods of QS and AS. Like-
wise, the percentage of time with SaO
2
less than
92% was calculated, and the number of dips in
SaO
2
of 4% or more per hour (4%-dip rate) was
calculated. A normal SaO
2
was taken as being
greater than 96%, a signicant apnoea/hypopnoea
was identied as a dip of 4% or greater below this
level (i.e. SaO
2
B92%) [15].
Based upon the qualitative and quantitative
analysis of the sleep study a diagnosis of the
severity of the respiratory problems as normal,
mild, moderate or severe UAO was made follow-
ing the criteria in Table 4 [12].
3. Results
3.1. Pattern of sleep
The sleep study breakdowns for individual
patients are given in Table 5. The duration of the
sleep studies ranged between 5.4 and 10.0 h (mean
8.3 h), with sleep efciencies between 65% and
100% (mean 93%). The number of awakenings
during sleep ranged from 0 to 7 per night (mean
1.5), with between 0% and 33% (mean 7%) of the
TIB spent awake. For the group overall, sleep was
divided approximately equally between quiet and
AS, with a mean of 44% (range 1464%) of TST
spent in QS and mean of 56% (range 3686%) in
AS.
3.2. Clinical score 6s sleep study score
The assessment of respiratory problems based
upon clinical history (Table 3) resulted in 12
patients being classied as having mild obstructive
respiratory problems during sleep, 10 as having
moderate, and 4 as having severe. Objective anal-
ysis of the sleep study data using our standardised
criteria (Table 3) classied 3 patients as normal,
with 8 cases of mild obstruction, 8 of moderate
OSA, and 7 of severe OSA. In 17/26 (65%) of
cases there was agreement between scores based
upon clinical history and those based upon the
sleep study, however, 2 patients (Nos. 7 and 13)
classied as mild based on clinical history were
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 131
Table 4
Observational and sleep study criteria used for scoring the severity of UAO during sleep
Clinical (video) observations Severity Sleep study criteria
Thoracic and abdominal signals in phase or slightly out of Slightly increased respiratory efforts Mild
phase
SaO
2
within normal limits (\92%) Usually mouth breathing
9Slight intercostal or suprasternal inspiratory 9Few brief mild dips in SaO
2
(never B90%)
recession
9Snoring without restless sleep
Moderate Thoracic and abdominal signals out of phase Moderately increased respiratory efforts
Usually mouth breathing Baseline SaO
2
within normal limits (\92%)
9Moderate intercostal or suprasternal inspiratory More frequent, repeated episodes of desaturation to the
mid-80s (%) recession
9Snoring and snorting with disrupted, restless
sleep
Severe Thoracic and abdominal signals out of phase Markedly increased respiratory efforts
Frequent, prolonged periods of paradoxical breathing Mouth breathing
Marked intercostal or suprasternal inspiratory Frequent, prolonged periods of arterial oxygen desaturation
recession
9Nasal aring
Loud snoring and snorting with disrupted, restless
sleep
found to be moderate by sleep study, whilst 3
patients (Nos. 20, 25 and 26) suspected of mild
OSA based on clinical history were found to be
within normal limits on sleep study. A further 3
patients (Nos. 3, 8 and 15) classied as moderate
from clinical history, were found to be severe
according to the sleep studies, whereas, 1 patient
(No. 19) diagnosed as moderate OSA from clini-
cal history was classied as mild according to the
sleep study.
3.3. Objecti6e respiratory sleep study results
Based upon our standardised criteria (Table 4)
patients were diagnosed as having UAO during
sleep ranging in severity from normal to severe.
Overall, 8 patients were classied as having mild
UAE during sleep, 8 moderate and 7 severe, the
remaining 3 patients were considered normal.
When considered by disease type, the 8 patients
with type IH MPS were scored as the most severe
for OSA with 5/8 cases classied as severe and 3/8
as moderate (Tables 6 and 7). The two patients
with type IHS MPS were both classied as having
moderate OSA. The 6 patients with type II MPS
had UAO severities ranging from mild to severe,
with 2 mild, 2 moderate, and 2 severe. Of the 3
patients with type IIIA MPS, 2 had mild and 1
had moderate OSA, whilst the patient with type
IIIB MPS was classied as normal. The 4 patients
with type IV MPS all had mild OSA, and the 2
patients with type VI MPS were both classied as
normal with respect to their breathing during
sleep.
The mean (range) of results for mean overnight
SaO
2
, mean 4% SaO
2
dip rate, %time SaO
2
B
92%, and mean number of 12 bpm PR rises/h for
each of the MPS types are given in Tables 6 and
7, whilst the mean values for individual patients
are shown in Fig. 1.
The severity of respiratory disturbance during
sleep varied with the clinical syndrome (see be-
low). Overall, respiratory problems were most
marked in MPS IH, followed by MPS types IHS,
and II. One patient with type IIIA (No. 17) also
had signicant respiratory disturbances during
sleep. The severity of the respiratory problems
was markedly lower in the other 3 patients with
MPS type IIIA and all the patients with MPS
types IIIB, IV and VI.
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 132
3.4. Mean SaO
2
The mean overnight SaO
2
for the group as a
whole was 94.0%, with values ranging between a
mean SaO
2
of 98.6% in the mildest case (No. 26)
and 78.6% in the most severe case (No. 4).
In terms of the sleep study scores for severity of
OSA, the mean (range) of SaO
2
value for patients
classied as normal was 97.8% (96.998.6%), with
a value of 96.4% (94.597.3%) for those classied
Table 5
Breakdown of sleep study results: TIB time in bed, TST total sleep time, W no. awakenings during sleep, SE sleep efciency,
QS quiet sleep (%TST), AS active sleep (%TST)
No. SE (%) TIB (h) QS (%TST) AS (%TST) TST (h) W
71 62 38 1 5.4 3.8 1
2 48 52 50 0 3.9 7.9
17 83 100 9.7 0 9.7 3
92 14 86 4 7.5 6.9 0
5.8 3 63 52 5 9.3 48
46 54 99 9.3 9.2 0 6
75 41 59 7 7.5 5.6 1
50 56 44 8 8.2 4.2 0
58 (17.7) 42 (17.7) 7.5 (20.4) 0.6 (1.1) Mean (S.D.) 6.1 (2.3) 8.1 (1.3)
3.89.7 03 50100 1462 3886 Range 5.49.7
49 9 51 6.7 100 0 6.7
86 44 56 3 7.0 6.1 10
93 (n/a) 48 (n/a) Mean (S.D.) 53 (n/a) 6.9 (n/a) 64 (n/a) 1.5 (n/a)
(n/a) (n/a) (n/a) Range (n/a) (n/a) (n/a)
59 96 2 41 8.4 8.9 11
77 57 12 43 9.9 7.6 3
8.4 57 13 43 6.6 79 0
14 24 76 54 3.7 6.7 7
75 38 62 15 10.0 7.5 4
100 24 16 76 10.0 9.9 1
Mean (S.D.) 9.0 (1.3) 7.3 (2.1) 2.8 (2.5) 80 (16.2) 41 (15.2) 59 (15.2)
2459 4176 54100 Range 07 3.79.9 6.710.00
100 54 17 46 6.3 4.1 0
9.9 2 87 52 48 18 8.6
9.8 0 95 46 54 19 9.3
49 (n/a) 51 (n/a) 94 (n/a) 0.7 (n/a) Mean (S.D.) 7.3 (n/a) 8.6 (n/a)
87100 4654 4654 Range 6.39.9 4.19.3 02
20 8.3 8.6 40 1 60 97
n/a n/a Mean (S.D.) n/a n/a n/a n/a
n/a n/a n/a Range n/a n/a n/a
7.4 1 99 64 36 21 7.3
22 88 8.0 43 57 7.1 1
6.8 64 23 36 5.6 82 5
24 28 72 99 7.9 8.0 1
92 (n/a) 43 (15.3) 57 (15.3) Mean (S.D.) 7.6 (n/a) 7.0 (n/a) 2.0 (n/a)
8289 2864 3672 Range 6.88.0 5.67.9 15
39 98 0 61 9.1 9.2 25
95 26 43 8.7 57 8.3 1
9.0 (n/a) 59 (n/a) Mean (S.D.) 41 (n/a) 97 (n/a) 0.5 (n/a) 8.7 (n/a)
n/a n/a Range n/a n/a n/a n/a
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 133
Table 6
Objective analysis of severity of UAO during sleep: Clinical history and sleep study scores for OSA given as severe (+++),
moderate (++), mild (+), normal ()
Clinical history Sleep study UAO score Mean SaO
2
SaO
2
4% dips/h No. %Time SaO
2
B92% Type
+++ +++ 1 92.8 IH 27.0 33.3
2 IH +++ +++ 87.3 7.1 97.8
++ +++ 90.5 3 21.2 IH 70.1
+++ +++ 78.6 IH 56.9 4 99.9
IH 5 ++ ++ 96.1 29.6 8.0
++ ++ 94.4 6 17.2 IH 10.8
+ ++ 94.7 IH 24.2 7 5.2
IH 8 ++ +++ 86.0 86.8 29.0
Mean (S.D.) 3+++, 4++ 5+++, 3++ 90.0 (5.85) 33.7 (25.74) 44.3 (39.54)
1+ 78.696.1 7.186.8 Range 5.299.9
9 IHS ++ ++ 92.5 7.7 34.9
++ ++ 95.5 10 18.5 IHS 15.8
2++ 2++ 94.0 13.1 Mean 25.3
Range 92.595.5 7.718.5 15.834.9
11 II +++ +++ 90.9 9.7 70.1
+ + 96.6 II 9.7 12 1.0
II 13 + ++ 96.1 6.3 0.8
II 14 ++ ++ 95.0 15.5 14.6
++ +++ 93.6 II 51.4 15 24.5
+ + 97.3 6.4 16 0.7 II
1+++, 2++ 2+++, 2++ 94.9 (2.34) 16.5 (17.4) Mean (S.D.) 18.6 (27.0)
Range 3+ 2+ 90.997.3 6.351.4 0.770.1
++ ++ 17 94.5 IIIA 4.1 28.1
+ + 96.7 IIIA 8.0 18 2.3
IIIA 19 ++ + 97.2 3.9 1.4
2++, 1+ 1++, 2+ 96.1 Mean 5.3 10.6
94.596.7 3.98.0 Range 1.428.1
20 IIIB + 97.7 1.2 0.1
1+ 1 n/a Mean n/a n/a
n/a n/a Range n/a
21 IV + + 96.5 1.0 0.2
22 IV + + 95.4 8.1 1.4
+ + 94.5 IV 5.3 23 4.2
IV 24 + + 96.7 6.9 0.7
4+ 4+ 95.8 Mean 5.3 1.6
94.596.7 1.08.1 Range 0.24.2
25 VI + 96.9 0.5 0
26 VI + 98.6 0.5 0
2+ 2 97.8 0.5 Mean 0
Range n/a n/a n/a
as mild, 94.5% (92.596.1%) for the moderate
cases, and 88.5% (78.693.6%) for the cases
classied as severe.
The mean (range) SaO
2
value for each of the
MPS types are given in Tables 6 and 7. In general,
patients with MPS types IH, IHS and II had the
lowest mean overnight SaO
2
values, whilst all the
patients with MPS types IIIA, IIIB, IV and VI
maintained their mean overnight SaO
2
s above
94%.
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 134
3.5. 4% SaO
2
dip rate
The mean 4% SaO
2
dip rate for the group as a
whole was 16.7 dips/h, with a range extending
from 0.5 dips/h in the mildest cases (Nos. 25 and
26) to 86.8 dips/h in the most severe case (No. 8).
In terms of the sleep study scores for severity of
OSA, the mean (range) 4% SaO
2
dip rate values
for patients classied as normal was 0.7 dips/h
(0.51.2), with a value of 6.2 dips/h (1.09.7) for
those classied as mild, 15.4 dips/h (4.129.6) for
the moderate cases, and 37.2 dips/h (7.186.8) for
the cases classied as severe.
The mean (range) of the 4% SaO
2
dip rate for
each of the MPS types is given in Tables 6 and 7.
The rates were highest in MPS types IH, IHS and
II, whilst the rates were found not to exceed 4
dips/h in patients with MPS types IIIA, IIIB, IV
and VI.
3.6. %Time SaO
2
B92%
The average %time SaO
2
B92% for the whole
study was 21.3%, ranging from 0% in the mildest
cases (Nos. 20, 21, 25 and 26) to 100% in the most
severe (No. 4).
When related to the sleep study scores for
severity of OSA, the mean (range) %time SaO
2
B
92% for the patients classied as normal was 0%
(00%), 1.5% (0.24.2%) for those classied as
mild, 14.8% (0.834.9%) for those classied as
moderate, and 60.7% (24.5100%) for the severe
cases.
The mean (range) of the %time SaO
2
B92% for
each of the MPS types is given in Tables 6 and 7.
The highest percentage times were found in pa-
tients with MPS types IH, IHS, and II, with
%time SaO
2
B92% values below 5% in all case of
MPS types IIIA, IIIB, IV and VI, excepting pa-
tient No. 17 who spent 28% of sleep time with
SaO
2
B92%.
4. Discussion
OSA syndrome was rst described in an adult
with MPS IS in 1980 [6] and is now well-recog-
nised in this condition; in one study 12/21 MPS
patients had symptoms suggestive of sleep apnoea
and 89% of those tested had OSA demonstrated
by polysomnography [2]. The consequences of
sleep apnoea in normal children include be-
havioural problems and learning difculties
Table 7
Alternate version of Table 6
Mean (range) Sleep study classication MPS Type
Mean SaO
2
(%) 4% SaO
2
dips/h %Time SaO
2
B92%
5 Severe IH 44.3 (5.2100.00) 90.0 (78.696.1) 33.7 (7.186.8)
3 Moderate
25.3 (15.834.9) 13.1 (7.718.5) 94.0 (92.595.5) 2 Moderate IHS
94.9 (90.997.3) 16.5 (6.351.4) II 18.6 (0.770.1) 2 Severe
2 Moderate
2 Mild
1 Moderate IIIA 96.1 (94.597.2) 5.3 (3.98.0) 10.6 (1.428.1)
2 Mild
1.2 (n/a) 97.7 (n/a) 0.1 (n/a) 1 Normal IIIB
95.8 (94.596.7) 5.3 (1.08.1) IV 1.6 (0.24.2) 4 Mild
2 Normal 97.8 (96.998.6) VI 0.5 (0.50.5) 0.0 (0.00.0)
All 7 Severe 94.0 (78.698.6) 16.7 (0.586.8) 21.3 (0.0100.00)
8 Moderate
8 Mild
3 Normal
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 135
Fig. 1. Mean overnight SaO
2
, 4% SaO
2
dip rate, and %timeB92 for all 26 patients. The patients are classied according to MPS
type. The sleep studies are displayed in total as (A) all sleep, and subdivided into sleep states as (B) QS and (C) AS. The classication
of severity of UAO based upon the sleep study are represented as () severe; () moderate; () mild; () normal.
[16,17], failure to thrive [16,17] and cardio-respira-
tory failure [18,19]. Children with MPS may have
these problems in the absence of OSA, but undi-
agnosed and untreated sleep apnoea may exacer-
bate their symptoms.
Clinical assessments are generally made on the
basis of the medical history taken from the par-
ents, physical examination of the patient, and
imaging of the upper airway. When interpreting
the physical examination of the patient, and the
imaging of the upper airway it is important to
bear in mind that during the assessment the child
may be either awake or sedated. By nature, the
condition of obstruction during sleep is state re-
lated, with increased likelihood of obstruction
during active (REM) sleep when physiological
tone of the upper airway muscles is lost [11].
Assessment of a child in the awake or sedated
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 136
state may fail to reveal the true extent of the
obstructive problem. A functional assessment
(cardio-respiratory sleep study) to assess upper
airway function during unsedated sleep forms an
important part of the diagnosis and assessment of
these patients. Furthermore, the results of the
present study suggest that whilst parental histories
are of value in the assessment of these cases with
agreement between clinical score based on
parental history and sleep study score in 17/26
cases, there are discrepancies with parents tending
to understate the severity of the OSA in the
moderate/severe cases (Tables 6 and 7) whilst over
estimating the severity in the normal/mild cases
(Tables 6 and 7). It is possible that the parents
perception of the importance or severity of the
respiratory problems may be affected by the com-
plexity of their childs condition.
The principal nding of the present study was
that a high proportion of patients studied had
signicant UAO during sleep, and that the sever-
ity of the obstruction was related to MPS type.
Overall, of the 26 patients studied, 7 had severe, 8
had moderate and 8 had mild UAO during sleep.
Only 3 patients had breathing that could be con-
sidered normal (Tables 6 and 7, Fig. 1). When
looked at in terms of MPS type, all 10 patients
with types IH (Hurler) or IHS (HurlerScheie)
had either moderate or severe OSA, whilst the 6
patients with type II (Hunter) were divided
equally between severe, moderate and mild cate-
gories. Patients with type IIIA (Sanllipo A) were
classied as either moderate (1) or mild (2), and
those with type IV (Morquio) were all mild (4).
The single patient with type IIIB (Sanllipo B)
and the 2 patients with type VI (Maroteaux-
Lamy) were all classed as normal. Whilst the
ndings appear consistent for types IH, IHS,
IIIA, IV and VI, those for type II are more varied
and cannot be explained, for example, by the
patients ages. Further studies in a larger group of
these patients are required to clarify the reasons
for the differences between the degree of obstruc-
tion in patients with the same MPS type. The
numbers of patients in groups IHS, IIB, and VI
are small, and further studies are indicated.
The predominant problem found in this group
of patients was obstructive apnoea/hypopnoea.
Whilst the most likely reason for obstruction in
these patients is an anatomical one with alteration
in the conformation and the compliance of their
upper airways, one cannot exclude the possibility
of abnormal neuromuscular control of upper air-
way patency during sleep.
We also examined the respiratory traces of
these patients for evidence of central apnoeas. In
all cases we found infrequent pauses in respiration
that were short and caused no signicant changes
in SaO
2
or HR. The number and frequency of
these pauses fell within the normal ranges de-
scribed by Guilleminault et al. [20] and Carska-
don et al. [21].
Clinically it has been recognised that a number
of children with MPS may have UAO during
sleep which may be anticipated from the anoma-
lous form of the upper airway [38] and copious
mucous secretions [9,10]. However, little objective
documentation exists on either the extent or sever-
ity of the problem.
The study was designed to ascertain the fre-
quency of respiratory problems during sleep in a
group of children with MPS. The majority (23/26)
of the children with MPS assessed had some
degree of respiratory disturbance during sleep;
overall, indicative of this, there was a reversal of
the normal ratio of AS to QS in 14/26 patients
(Table 5). This can be partly explained by a
suppression of QS (deep), which has been de-
scribed as a feature of paediatric sleep apnoea
[22], with probably an additional over-classica-
tion in the present studies using behavioural crite-
ria of AS to include periods of Stage 1 and 2
(light) sleep. It is recognised that obstructive res-
piratory problems predominate during REM, and
Stages 1 and 2 sleep in children [15]; the repeated
obstructive episodes and subsequent arousals dur-
ing Stages 1 and 2 sleep are likely to lead to a
misclassication of these periods as AS when us-
ing behavioural criteria for staging. Sleep prob-
lems were more severe in the syndromes
recognised to have earlier and more pronounced
manifestations of disease (MPS types IH, IHS and
II; Tables 6 and 7, Fig. 1). The severity of UAO
did not seem to be related to age.
A number of therapeutic options have been
reported as successful in the management of OSA
S.E.J. Leighton et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 127138 137
in MPS. These include adenotonsillectomy [23],
bone marrow transplantation [4,24], and n-CPAP
[25]. Each has its disadvantages; for example, the
perceived risk of anaesthesia accompanying ade-
notonsillectomy [26], the risks of bone marrow
transplantation and the difculty of administering
n-CPAP in children. In order to establish the
benets of these interventions more precisely,
scoring systems may prove invaluable. Adenoton-
sillectomy may not always be successful or any
benet achieved may not be maintained [3]. The
outcome obviously depends on the role any ade-
notonsillar hypertrophy is playing in the complex
multifactorial airway obstruction in an individual.
Anecdotal success has also been claimed for tra-
cheostomy [2,6,10] although Ginzburg claims that
n-CPAP, reportedly effective in an adult with
MPS II, is more likely to be successful because of
the diffuse nature of the airway involvement [25].
There are no universally accepted minimum
diagnostic criteria for OSA in children concerning
frequency and duration of obstructive apnoeas.
However, respiratory problems during sleep may
be regarded as a continuum; dening OSA syn-
drome as present or absent based on the apnoea/
hypopnoea index may not be relevant in the
clinical management of patients. Therefore we
have graded respiratory problems during sleep as
absent, mild, moderate or severe both on clinical
grounds and on sleep study results. A poor corre-
lation between clinical and laboratory-based scor-
ing systems has been found before [27] and is
conrmed in this study. This suggests that a clini-
cal scoring system alone is unlikely to prove reli-
able, either for baseline assessments, or for
long-term follow-up. Nevertheless, it may be a
useful adjunct, particularly for patients in whom a
formal sleep study proves impossible owing to
non-compliance.
The laboratory-based system, on the other
hand, could prove to be useful, both to assess
severity of obstruction as well as to evaluate
prospectively any therapeutic intervention, thus
enabling clinical services guidelines to be devel-
oped. Larger numbers of patients, both collec-
tively and within individual subgroups, will need
to be studied in order that our ndings can be
validated. However, they have encouraged us to
embark on a prospective study of therapeutic
intervention in these patients.
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