2008 Wiley-Liss, Inc.

American Journal of Medical Genetics Part A 146A:1286 1295 (2008)

Growth Charts for Patients Affected

With Morquio A Disease
o,1 Shunji Tomatsu,1* Ana Brusius,1 Mary Smith,2 and Tadao Orii3
Adriana M. Montan
1

Department of Pediatrics, Saint Louis University, St. Louis, Missouri

2
International Morquio Organization, Phoenix, Arizona
3
Department of Pediatrics, Gifu University, Gifu, Japan
Received 10 September 2007; Accepted 15 December 2007

Children with Morquio A disease grow poorly and become

physically handicapped because of systemic bone disease.
The purpose of this study was to describe observed growth
patterns and their relationship with the physical condition of
patients with Morquio A. In a one-center study, questionnaire-based longitudinal and cross sectional data were used
to develop growth curves, to assess physical activity and to
determine the incidence of surgical procedures in 354
patients with Morquio A. Mean birth lengths of boys and
girls were 52.6 and 52.1 cm, respectively. The mean final
heights for males and females at 18 years and older were
122.4
21.5 and 113.1
22.6 cm, respectively. These results
corresponded to 7.4 SD for males and 7.7 SD for females

compared to the normal healthy controls. Mean birth weights

for boys and girls were 3.59
0.58 and 3.5
0.7 kg,
respectively. The mean body mass index for males and
females at over 18 years of age was 24.7
6.1 and
25.6
5.4 kg/m2, respectively. The growth pattern in
Morquio A patients was characterized by impaired growth
velocity after 1 year of age. This is the first report providing
growth charts for patients with Morquio A, which can help
with monitoring the disease and assessing the clinical
efficacy of treatments. 2008 Wiley-Liss, Inc.

Key words: Morquio A disease; growth; MPS IVA; GALNS

o AM, Tomatsu S, Brusius A, Smith M, Orii T. 2008. Growth

How to cite this article: Montan
charts for patients affected with Morquio A disease. Am J Med Genet Part A 146A:12861295.

INTRODUCTION

Mucopolysaccharidosis IVA (MPS IVA; Morquio A

disease: OMIM#253000) is a lysosomal storage
disease in which affected individuals lack the
enzyme, N-acetylgalactosamine-6-sulfate sulfatase
(GALNS, EC: 3.1.6.4). This enzyme hydrolyzes the
sulfate moiety of the glycosaminoglycans (GAGs)
namely, keratan sulfate (KS) and chondroitin-6sulfate (C6S). In absence of this enzyme, the stepwise
degradation of KS and C6S is blocked, resulting in the
intracellular accumulation of the respective GAG in
the lysosomes of a wide range of tissues [Singh et al.,
1976].
Prevalence of Morquio A disease is approximately
1 in 250,000 live births, but the incidence varies
widely among countries [Lowry et al., 1990; Meikle
et al., 1999; Poorthuis et al., 1999; Applegarth et al.,
2000; Baehner et al., 2005]. There are several studies
that have documented the incidence of Morquio A;
the highest is 1 in 76,000 live births in Northern
Ireland [Nelson, 1997], and the lowest is 1 in 450,000
live births in Portugal [Pinto et al., 2004]. The concept
of a founder effect accounts for the discrepancy of
the incidence in different ethnic populations.

More than 150 different mutations in the GALNS

gene have been identified so far. Over 70% of the
known lesions in the GALNS gene derive from
missense mutations [Tomatsu et al., 2006]. This
heterogeneity in GALNS gene mutations accounts
for extensive clinical variability of Morquio A [Orii
et al., 1981; Fukuda et al., 1992; Hori et al., 1995;
Ogawa et al., 1995; Kato et al., 1997; Yamada et al.,
1998; Terzioglu et al., 2002; Montano et al., 2003,
2007a; Tomatsu et al., 2005].
Affected infants seem normal at birth but will
progress to an advanced stage of the disease within
a few years. Over 70% of patients affected with
Morquio A have initial clinical manifestations within
the first 23 years of life although the formal
diagnosis is usually delayed until about 2 years later
[Montano et al., 2007b]. Children with Morquio A

Grant sponsor: International Morquio Organization.

*Correspondence to: Shunji Tomatsu, M.D., Ph.D., Department of
Pediatrics, Saint Louis University, Doisy Research Center Room 307, 1100
South Grand Blvd., St. Louis, MO 63104. E-mail: tomatsus@slu.edu
DOI 10.1002/ajmg.a.32281

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GROWTH CHARTS FOR PATIENTS WITH MPS IVA

exhibit heterogeneity in their phenotypes from

attenuated features to severe systemic bone involvement. Skeletal abnormalities observed during early
childhood include: short trunk dwarfism, odontoid
hypoplasia, pectus carinatum, kyphosis, scoliosis,
genu valgum, coxa valga, hypermobility of joints,
and abnormal gait. Generally, Morquio A patients
exhibiting a severe phenotype do not survive
beyond the second or third decade of life. In contrast,
patients with an attenuated phenotype have been
reported to survive into the seventh decade of life
[Montano et al., 2007b].
Currently no medications are available to prevent
or cure the progressive disease. Surgical interventions may be required to improve the quality of life of
the patients. A recent study based on the information
provided by 326 Morquio A patients showed that
on average, by 5 years of age, Morquio A patients
often require surgical procedures such as adenoidectomy and tonsillectomy. Thereafter, at 10 years of
age the patients undergo major surgical operations
in neck, hip, knee, and leg regions [Montano et al.,
2007b].
Short stature is a critical feature of Morquio A. The
growth retardation of children with classical Morquio
A starts in early childhood and their growth nearly
stops around 7 or 8 years of age, although some
patients with an attenuated phenotype continue
growing into their teens [Montano et al., 2007b]
or even have a normal height [Beck et al., 1986;
Montano et al., 2007a]. The current criteria to
determine the clinical severity in Morquio A are
based on growth and final height. Since growth and
final height differ markedly between Morquio A and
healthy children, standard growth charts should not
be used for children affected with this disorder.
Several syndrome-specific charts have been
described previously including those for Down
[Myrelid et al., 2002], Noonan [Witt et al., 1986],
PraderWilli [Butler and Meany, 1987], Turner
[Gawlik et al., 2006], and Williams syndromes [Martin
et al., 2007], but no charts have been reported for any
mucopolysaccharidoses.
Overall, growth is a fundamental and integral
marker in children with Morquio A. Children with
Morquio A are known to grow poorly compared
to age-matched healthy children, but it is unclear
whether this poor growth is normal for the
Morquio A population or a marker of some secondary condition that requires further evaluation and
treatment. The basic clinical questions are: (1) does
the observed poor growth negatively impact
health of children with Morquio A? and (2) if
growth is improved, are health and well-being also
improved?
However, appropriate growth curves for these
children with Morquio A have not been established.
In this report we describe (1) growth charts based on
a large population of Morquio A patients enrolled in

the International Morquio Registry and (2) the

correlation between growth and markers of health
and physical activity.

MATERIALS AND METHODS

Study Subjects

The details of subject identification, recruitment,

and enrollment were fully described previously
[Montano et al., 2007b]. Briefly, the patients diagnosed with Morquio A were asked to participate in
the International Registry through the registrys web
site (www.morquio.com). The International Morquio Organization (IMO) and our research team
collaboratively created a questionnaire for all members who have Morquio A. The study was approved
by the Institutional Review Boards (IRBs) of the IMO
and Saint Louis University. Between August 1998 and
May 2007, 354 patients or their parents gave informed
consent and returned a completed questionnaire.
A self-completion questionnaire covering each
patients medical history and current situation was
developed. The questions included height and
weight history information, physical activity (walking distance, wheelchair use), and health condition
(incidence of major surgical procedures in neck,
spine, hip, knee, leg, and ankle). Patients provided
information about diagnostic age and the name
and the affiliation of the physician who made the
diagnosis. The clinical and laboratory diagnoses of
the respondents were verified. In order to obtain
confirmatory information from the group of nonresponders to some questions, the board members of
IMO and specialists called or e-mailed to them. The
diagnosis of MPS IVA was confirmed by the enzyme
assay of GALNS (<5% of the enzyme activity in
normal controls).
As a consequence, this study was based on the data
obtained from 354 MPS IVA patients enrolled from 43
countries, Height (n 1,769) and weight (n 1,510)
measurements from 166 girls and 188 boys with
Morquio A were collected. The measurements of
height and weight were obtained from the growth
charts provided by the physicians and were confirmed for all patients. In addition, copies of the
original growth charts provided by the physicians
were obtained for 10% of the patients to confirm the
chronological data deposited in the questionnaire.
Longitudinal data were obtained from 85% of the
patients. Measurements of height in patients were
performed in a standing position. Height measurement was fairly objective, though height might be
affected by different structural abnormalities that
influence how erect one can stand. Since this disease
is so rare and the patients are spread all around the
world, it was not possible to gather the patients in a
few centers to make the measurements.

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The measured value for height in patients over

18 years was considered unchanged. Therefore, the
data from Morquio A patients over 18 years old were
grouped as data at 18 years. No Morquio A patients in
this study were treated with growth hormone.
Statistical Analysis

The data used for the construction of the growth

charts were age (years and months), height (cm),
and weight (kg). The body mass index (BMI) was
calculated by dividing the weight by the square
length or height (kg/m2).
The centile curves for height, weight, and BMI
were derived by using LMS ChartMaker Pro version
2.3 software (Medical Research Council, UK) [Cole
and Green, 1992; Cole et al., 1998].
As described by Cole and Green [1992], the
distribution of height and weight at each age was
determined by three parameters namely, the BoxCox power transformation (L), the median (M), and
the coefficient of variation (S). The values of L, M, and
S changed smoothly with age providing values that
could be used to construct the centile curves. The
obtained reference curves were compared with
those of healthy children provided by the Centers
for Disease Control and Prevention (CDC).
MannWhitney test was performed for comparisons between the patient groups with and without a
history of surgical procedures.
RESULTS
Study Population

Data were collected regarding 354 Morquio A

patients (188 males, 53%; 166 females, 47%). Seventy
percent of the patients were from a Caucasian
background, followed by patients with Hispanic
(17%), Asian (11%), Black (1%), and other (1%)
origins.

The geographic distribution of patients involved in

this study was predominantly as follow: United States
(n 94, 26.5%), Italy (n 38, 10.7%), Germany
(n 34, 9.6%), Canada (n 23, 6.5%), Japan (n
17, 4.8%), Brazil (n 14, 3.9%), Poland (n 13,
3.7%), Colombia (n 10, 3.1%), Spain (n 10, 3.1%),
and other countries with a percentage below 3%
(n 99, 27.9%).
Length and Height

The mean of longitudinal measurements per

patient was 4.6 (SD 4.9, median 3). The mean
of birth length for boys and girls was 52.5
4.0 cm
(n 144) and 52.1
3.0 cm (n 111), respectively,
which corresponded to 1.1 SD for boys
(50
2.7 cm) and 1.4 SD for girls (49.3
2.2 cm)
on the CDC growth charts (Table I).
Until 2 years of age, the 50th centile length/height
of boys and girls with Morquio A closely corresponded to that of the normal population (Figs. 1
and 2). However, at 4 years of age the mean height
of both genders started to fall markedly below the
2 SD value. At 13 and 14 years of age the values
for boys with Morquio A were constant at 5.2 SD
when compared to the height for normal healthy
boys (Table II). The mean height for males at 18 years
old was 122.4
21.5 cm (n 75), resulting in difference of 53.7 cm compared to the mean average for
the age-matched controls. This value corresponded
to 7.4 SD of the height for normal healthy males.
The tendency for girls was similar to that of the boys.
At 8 and 9 years of age the mean height remained
constant with 5.3 SD when compared to the height
for normal healthy girls. At 16 years of age, the mean
height for girls reached 9.2 SD compared to the
normal values for girls. The mean height for females
at 18 years old was 113.1
22.6 cm (n 143),
resulting in difference of 49.9 cm compared to the
mean height for the age-matched controls. This value
corresponded to 7.7 SD of the height for normal
healthy females. Final heights of patients at 18 years

TABLE I. Length in Morquio A Disease Until 12 Months of Age

Boys
Age (months)
0
1
2
3
4
5
6
7
8
9
10
11
12

Girls

Mean (cm)

SD

Age (months)

Mean (cm)

SD

144
6
12
10
10
2
12
7
4
9
2
1
59

52.55
56.03
59.82
63.96
67.93
69
71.6
75.4
73.25
75.01
78.85
80.6
77.84

4.04
2.18
3.36
3.34
3.67
5.65
3.45
4.13
4.65
3.89
7.28
0
5.07

0
1
2
3
4
5
6
7
8
9
10
11
12

111
3
8
5
6
2
9
0
3
4
2
3
35

52.07
55.43
58.68
62.18
66.6
68
71.8
NA
73.5
74
76
75.33
78.79

3.04
1.91
2.52
2.94
1.94
0.7
1.91
NA
1.8
2.94
2.82
3.05
3.92

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TABLE II. Height in Morquio A Disease
Males

Females

Age (years)

Mean (cm)

SD

Age (years)

Mean (cm)

SD

2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18*

75
62
58
49
45
47
38
38
35
22
26
25
16
23
21
20
75

85.06
90.39
93.11
96.95
100.48
104.06
107.08
109.32
109.42
114.04
114.62
115.65
120.86
118.23
119.35
123.32
122.41

5.12
5.3
6
8.23
9.73
11.4
12.46
14.34
14.37
15.44
19.18
20.09
20.88
22.21
22.97
24.22
21.46

2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18*

38
35
39
41
32
28
31
35
26
28
29
27
27
19
23
22
143

84.13
86.71
90.22
93.73
96.25
97.03
97.85
101.07
102.14
102.65
108.23
105.23
101.69
102.94
103.42
107.48
113.14

3.72
3.91
4.84
6.91
7.21
8.23
9.34
12.69
14.12
15.2
18.03
18.23
12.05
14.4
12.98
18.62
22.6

*Includes patients 18 years of age and older.

old for both genders were compared to patients over

18 years of age, resulting in no significant difference.
Thus, secular influences were minimal in final
heights of Morquio patients.

The height velocity curve (mean) of Morquio A

patients is depicted in Figures 3 and 4. For boys with
Morquio A, the height velocity was average during

the first year of life and declined thereafter as rapidly

as that for healthy children. The growth spurts for
Morquio A patients were reduced compared to those
for normal healthy controls. There were three
accelerated peaks between 10 and 11 years of age,
at 13 years of age, and between 16 and 17 years of
age. For girls with Morquio A, the height velocity
dropped fast at 6 months old unlike that for
age-matched healthy controls. Subsequently, we
observed the spurts between 8 and 9 years of

FIG. 1. Growth charts for length/height (cm) of boys with Morquio A from
birth to 18 years of age. The dotted line shows the 50th centile values for normal
boys.

FIG. 2. Growth charts for length/height (cm) of girls with Morquio A from
birth to 18 years of age. The dotted line shows the 50th centile values for normal
girls.

Height Velocity

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FIG. 3. Growth velocity (cm/year) throughout childhood and adolescence

of boys with Morquio A. The gray line shows the height velocity values for the
normal boys.

age and between 11 and 12 years of age. However,

we observed a slow incremental change from 14 to
18 years of age unlike boys with Morquio A.
Weight-for-Age and BMI

Tables III and IV describe the values of weight-forage for Morquio A patients. Table III gives the values
of weight for boys and girls from 0 to 12 months of
age. The mean of birth weight for boys or girls was
3.6
0.6 kg (n 164) and 3.5
0.7 kg (n 137),
respectively, while the mean of birth weight for
normal healthy boys or girls was 3.5
0.6 and
3.4
0.5 kg, respectively, on the CDC growth charts.
Thus, the birth weight of Morquio A patients was a
little heavier than that of normal controls. The weight
of children with Morquio A disease up to age 12 years
was within the 2 SD of the normal children.
Thereafter, most children with Morquio A gained
weight gradually. The mean weight of males and
females with Morquio A at 18 years was 37.6

13.4 kg (n 56) and 35.8
14 kg (n 75), respectively. These values corresponded to 3.5 SD and
3.1 SD of the weight for age-matched normal males
and females (Figs. 5 and 6).
The average BMI for Morquio A males and females
over 18 years of age was 24.7
6.1 and 25.6
5.4 kg/m2,
respectively. These values corresponded to 1.3 SD
and 1.9 SD of the BMI for age-matched normal

FIG. 4. Growth velocity (cm/year) throughout childhood and adolescence

of girls with Morquio A. The gray line shows the height velocity values for the
normal girls.

males and females. BMI above the 95th centile

indicating overweight (34.7 and 34.4 kg/m2 for males
and females, respectively) was observed in 6.8% of
the males and 5.4% of the females with Morquio A of
18 years of age and older (Figs. 7 and 8). BMI above
the 85th centile (31.9 and 32.4 kg/m2 for males and
females, respectively), indicating patients at risk of
overweight, was observed in 15.2% of the males and
9.5% of the females with Morquio A of 18 years of age
and older.
Height, Weight, and Physical Activity

Correlation between final height and physical

activity of Morquio A patients was analyzed based
on the absence or presence of major surgical
procedures. Presence of surgical procedures was
independent of the height of the patients. We did not
observe significantly increased heights in those
patients with fewer surgical procedures (data not
shown).
There was a tendency for patients with heights
between 80 and 100 cm to have a reduced capacity
for walking distance between 0 and 400 m regardless
of the presence or absence of a history of surgical
intervention(s). Among the Morquio A patients over
130 cm tall, who had undergone surgery walked a

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TABLE III. Weight in Morquio A Disease Until 12 Months of Age
Boys
Age (months)
0
1
2
3
4
5
6
7
8
9
10
11
12

Girls

Mean (kg)

SD

Age (months)

Mean (kg)

SD

164
7
14
9
10
3
14
9
5
9
4
2
66

3.59
4.56
5.96
6.69
8.5
8.28
9.04
9.22
9.1
9.97
10.02
10.1
10.62

0.58
0.63
1.59
1.09
1.77
0.31
1.51
1.41
0.93
1.65
1.06
1.69
1.63

0
1
2
3
4
5
6
7
8
9
10
11
12

137
3
6
4
5
1
9
0
3
3
2
3
32

3.53
3.87
5.03
5.85
7.08
6.7
9.38
NA
10.93
9.33
9.1
9.19
10.7

0.69
0.21
0.83
0.72
0.82
0
3.5
NA
4.6
0.57
0.42
2.26
2.07

shorter distance (0200 m) than those without any

history of surgery (over 800 m) (z 3.2, P 0.0005).
Walking aid was required in almost all Morquio A
patients regardless height and weight. Eighty-five
percent of patients who required walking aid
underwent surgeries. Use of a wheelchair was
broadly distributed among Morquio A patients with
widely ranging statures. There were no wheelchairbound cases among over 130 cm patients who had
not undergone surgery (n 14). All bedridden
Morquio A patients were associated with a history
of surgical procedures (n 5).
Eighty-one percent (n 13) of overweight Morquio A patients (above 85th centiles termed as a risk
of overweight) had limited physical activity (walking distance was between 0 and 200 m). In addition,
66.7% of wheelchair-bound males (n 6) and 57.2%
wheelchair-bound females (n 4) were at risk of
overweight.

DISCUSSION

In this study, we made growth charts from birth to

18 years of age for patients with Morquio A. Our
study showed that the newborn body length and
weight in Morquio A appear similar or even slightly
increased compared to those of the normal population. This finding makes diagnosis of Morquio A at
birth a difficult task unless some bone deformities
associated with a skeletal dysplasia are recognized.
The growth pattern of MPS IVA patients is
characterized by impaired growth velocity after
1 year of age. The difference in the pattern of the
velocity at certain ages in comparison with that of
normal controls could be corrected by adding more
data to increase the size of the study group. The
individuals with Morquio A reached their final height
approximately at 11 years of age for males and 9 years
of age for females. We observed taller final heights

TABLE IV. Weight in Morquio A Disease

Males

Females

Age (years)

Mean (kg)

SD

Age (years)

Mean (kg)

SD

2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18*

65
58
54
44
41
40
38
34
31
17
23
13
9
14
12
11
56

12.54
14.27
14.98
16.09
17.33
18.73
20.52
23
25.67
26.65
26.9
30.06
34.86
31.94
30.72
34.02
37.64

1.66
1.94
2.1
3.09
3.42
3.96
4.54
6.63
6.49
7.82
8.7
11.93
10
12.32
11.46
9.56
13.42

2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18*

37
34
33
36
27
22
24
28
19
19
17
15
16
7
8
9
75

11.82
12.72
13.78
14.78
16.47
16.81
17.92
19.64
22.88
23.99
27.61
25.87
24.19
23.16
23.38
31.22
35.77

1.85
1.9
1.76
2.3
3.08
2.95
3.82
5.36
7.95
10.82
10.31
11.76
6.36
3.87
3.61
10.16
14

*Includes patients 18 years of age and older.

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FIG. 5. Body weight (kg) of males with Morquio A. The dotted line shows the
50th centile values for normal males.
FIG. 6. Body weight (kg) of females with Morquio A. The dotted line shows
the 50th centile values for normal females.

FIG. 7. Body mass index [weight (kg)/height2 (m2)] for males with Morquio
A. The dotted line shows the 50th centile values for normal males.

FIG. 8. Body mass index [weight (kg)/height2 (m2)] for females with Morquio
A. The dotted line shows the 50th centile values for normal females.

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GROWTH CHARTS FOR PATIENTS WITH MPS IVA

for both genders at 18 years of age, since the

continually increasing height data from attenuated
Morquio A patients contributed disproportionately
to the total. This study also showed that individuals
with Morquio A had a reduced pubertal growth spurt,
contributing to marked short stature. Some studies of
other genetic diseases showed the same phenomena
[Myrelid et al., 2002].
Two limitations of our study are: (1) Morquio A
disease is quite rare, leading to limited number of
data from each individual population, and (2)
collected data in this study contain patients from
diverse ethnic backgrounds. One argument is how
we can compare our current data with a normal
control population. One would like to compare the
growth charts on the same ethnic background. It
would be also ideal to have growth charts considering different socioeconomic background for each
population. However, current growth charts do not
exist to cover all of the relevant populations. Recent
studies made a compromise by comparing the
growth charts from a certain small population with
those from non-specific normal populations like
CDC growth charts [Clementi et al., 1999; Hauffa
et al., 2000; Marinescu et al., 2000; Erkula et al.,
2002; Ayatollahi and Pourahmad, 2006]. Therefore,
in this study we have selected CDC growth charts
which include update reliable data containing
diverse ethnic backgrounds [Kuczmarski et al.,
2002; Ogden et al., 2002]. We expect that in the
future the databases will be improved by including
higher variation of normal population for better
comparison purposes. In spite of limitations of
data, comparison with the CDC normal growth
charts led us to conclude that the severe growth
impairment of children with Morquio A occurs after
1-year old.
In pediatric practice, poor growth is equated
with poor health. Infant growth is a determinant of
adult bone mass, and poor childhood growth is a risk
for adult hip fracture [Oliver et al., 2007]. Poor growth
is determined by careful measurement and comparison of the results to appropriate reference standards.
Standard curves developed for the general population cannot be used to assess the growth of an
individual affected by Morquio A disease. For this
reason, efforts have been made to develop growth
curves specific for Morquio A. The primary measures
used are stature (height or length), body mass
(weight), and often body proportion (BMI). Growth
charts specific for Morquio A help clinicians evaluate
the body size (stature and weight) and relative
proportions (BMI) of an individual affected child
compared with reference data.
Previously the attenuated and severe phenotypes
for Morquio A patients were classified based on
genotype and height. The resultant phenotypic
classification according to height for classical (severe)
Morquio A was below 120 cm and above 120 cm for the

1293

attenuated type. This study showed that we have also

to take in consideration the gender to classify Morquio
A patients. The mean final height for females is shorter
than that for males (Table II). We propose that the
standard growth chart for each gender of Morquio A
patients should be used to define a more accurate
phenotypic classification. There are reports of patients
with a relatively normal height which reflect the
phenotypic variation of Morquio A [Beck et al., 1986;
Montano et al., 2007a]. According to the isopleth upon
which the patient falls, patients above the 90th centile
on the growth chart for each gender are more likely to
be defined as attenuated.
We associated the physical condition of the
patients, as a marker of health, with their growth.
There was a tendency for patients with short stature
to walk a shorter distance when compared to those
with greater stature. In addition, patients with greater
stature who underwent surgical procedures could
walk less when compared to those who did not have
any kind of surgical procedures. Since it is known
that lack of exercise could lead to psychological and
physical setbacks in any individual, monitoring
exercise is critical for patients with generalized bone
dysplasia like Morquio A patients.
Although the mean weight for Morquio A patients
over 18 years was considerably lighter than the
normal population, 6.8% and 5.4% of males and
females were overweight in the Morquio A population. We also found that most wheelchair-bound
patients were at risk of overweight or indeed,
obese. BMI is considered the best available weightstature index in both children and adults, independent of stature, correlation with body fat, and
prediction of mortality [Nysom et al., 2001]. It is
important to compare the measurements of BMI
with adequate sex- and age-specific reference
values. In this study, we observed that there was
an upward shift of the mean of BMI for both males
and females with Morquio A when compared to the
normal population. In addition, we found the 95th
centile values of 34.7 and 34.4 kg/m2 for males and
females with Morquio A, respectively. These values
are considered as overweight or pre-obese for
Morquio A patients at 18 years of age and older. The
95th centile values of the normal population are
28.9 kg/m2 for males and 30.3 kg/m2 for females,
indicating that the BMI of Morquio A patients is
higher when compared to values of the normal
population.
Morquio A patients with marked short stature
should avoid obesity. There is some consensus that,
in addition to the risks posed by obesity in the
general population, extra weight in those with severe
bone dysplasia may cause stress on susceptible
bones and joints, resulting in premature neurological
and orthopedic complications. Joints in Morquio A
patients are already impaired mainly from epiphyseal dysplasia caused by incomplete endochondral

American Journal of Medical Genetics Part A

1294

O ET AL.
MONTAN

ossification of epiphyseal cartilage. Cartilage with an

abnormal ossification process is fragile, and joints
tend to degenerate rapidly and develop early
arthrosis leading to surgical intervention such as
joint replacement [Kanazawa et al., 2001], especially
in the weight-bearing lower extremities. In general
overweight is a risk factor that will contribute to the
deterioration of Morquio A patients health.
In some genetic diseases, hypogonadism or
insufficient GH secretion can explain reduced
pubertal growth in patients. However, in Morquio
A patients no statistical analyses of GH values with
age have been performed to prove that there is
evidence of GH deficiency in Morquio A. At this
point, there is no evidence that growth hormone
treatment provides a beneficial effect for this disease.
Advanced treatments for Morquio A are currently
being developed including enzyme replacement
therapy. Such treatment may improve the quality of
life by slowing down the underlying disease process
of MPS IVA and preventing further damage of
targeted organs. The efficacy of the treatment has
to be evaluated carefully by monitoring several
clinical end points. The evaluation of growth pattern
before and after treatment will be one of the
important end points.
Our charts can be used to evaluate the spontaneous
growth pattern in the Morquio A population. Growth
charts specific for children with Morquio A are
therefore important tools in medical surveillance as
well as in the monitoring of growth promoting
treatments.
Understanding the impact of growth on health and
physical condition will require more careful measurements and a larger sample size to demonstrate
more statistically significant results. Currently there
are no standardized measurement techniques for
patients with Morquio A disease by each individual
physician. We are trying to define the standards
through the planned Natural History Program and
Enzyme Replacement Therapy clinical trials. A board
of experts from the field of mucopolysaccharidoses
research will review the findings. Nevertheless, we
feel that the current data are suggestive and worthy of
correlation between growth and physical activity in
Morquio A patients.
In conclusion, children with Morquio A have poor
growth compared with typical children. We have
developed growth curves for children with Morquio
A and correlated growth with markers of health and
physical condition. Taller children with Morquio A
had better health and physical status than shorter
children. Further studies are needed to corroborate
these findings and to evaluate whether specific
interventions can improve growth, as well as health
and physical activity. Determining the potential role
of these growth curves in clinical decision-making
will require additional clinical study.

ACKNOWLEDGMENTS

This study was supported by grants from Arianas

Cure Fund for Morquio, the Austrian Research
Society for Mucopolysaccharidoses and Related
Diseases, Bennett Foundation, Care for Carly Foundation, Care for Sota Morquio Foundation, German
MPS Society, International Morquio Organization
(Carol Ann Foundation), Italian MPS Society, Jacob
Randall Foundation, Miracle for Eddie Foundation,
National MPS Society, Muconetwork, and Spanish
MPS Society. We would like to thank Gary S.
Gottesman, M.D. for his editorial advice, Mariana
Goldim for her assistance, and Dr. Raoul Hennekam
for his valuable comments on the manuscript.
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