Morquio A: Burden of Disease

Report
Morquio A:
Burden of disease
Morquio A is a multisystemic disorder
Clinical manifestations:
Skeletal dysplasia
Short stature
Cervical spine instability
Spinal cord compression
Impaired endurance
Respiratory disease
Hearing loss
Corneal clouding
Heart valvular disease
Dental abnormalities
Normal intelligence
Morquio A is progressive
3 mo
4 yr
3 yr
10 yr
7 yr
16 yr
14 yr
17 yr
18 yr
26 yr
28 yr
30 yr
Morquio A disease process leads to progressive multisystemic manifestations
Patients typically require surgery
30%
25.5%
25%
22.2%
% Subjects
20.1%
20%
18.5%
17.5%
15%
10.8%
9.2%
10%
5.5%
5%
0%
Ear tube
insertion
Adenoidectomy
Spinal
decompression
Osteotomy
Spinal fusion
surgery
Tonsillectomy
Epiphyseal
surgery
Hip surgery
n = 325 Morquio A subjects (mean age= 14.5 years)
Data based on medical history reviews
> 70% of 325 Morquio A subjects had at least one surgical procedure
MorCAP baseline data
Harmatz et al, Mol Genet Metab, 2013
Mobility is compromised
Use of wheelchairs and walking aids is common
MorCAP baseline data (Harmatz et al, 2013)
revealed:
– 49% of 300 Morquio A subjects required
wheelchairs (mean age= 14.5 years)
– 26% of 298 Morquio A subjects used walking
aids (mean age= 14.5 years)
Data from the International Morquio A Registry
(Montano et al, 2007) revealed:
– 31% of 326 Morquio A patients needed
wheelchairs (mean age = 14.2 ± 11.1 years)
– 19% of 326 Morquio A subjects used walking
aids (mean age = 14.2 ± 11.1 years)
Harmatz et al, Mol Genet Metab, 2013; Montano et al, J Inherit Metab Dis, 2007
Patients often experience difficulties in
activities of daily living
Upper limb abnormalities contribute significantly to
activity limitations
Wrist hypermobility and weak hand grip cause difficulties with
tasks requiring strength, such as lifting heavy objects and
pouring from a bottle (Aslam et al, 2012)
MorCAP baseline data (Harmatz et al, 2013) revealed
limitations in patients’ ability to perform day-to-day tasks
– Of the 153 Morquio A subjects ≥ 12 years of age:
– 30% could not cut their fingernails
– 22% could not tuck in shirts
– 22% were unable to open jars
– 20% were unable to tie shoelaces
Aslam et al, JIMD Rep, 2013; Harmatz et al, Mol Genet Metab, 2013; BioMarin data on file
Endurance is impaired
Mean 6MWT
220
35
218
Steps/min
205
200
193.1
195
30
24.1
25
210
m
31.6
30
212.6
215
Mean 3MSCT
20
15
10
190
5
185
0
180
Age ≤ 18 years
n=248
Age > 18 years
n=68
All
n=316
Age ≤ 18 years
n=215
Age > 18 years
n=59
Mean 6MWT = 212.6 ±152.2 m (n = 316 subjects)
Mean 3MSCT = 30.0 ±24.0 stairs (n= 274 subjects)
MorCAP baseline data
Harmatz et al, Mol Genet Metab, 2013
All
n=274
Patient quality of life declines
with disease progression
In Morquio A, patient quality of life is compromised by:
deteriorating vision, hearing, and oral health
progressive musculoskeletal, cardiac and respiratory
impairments
decreasing mobility and endurance
increasing dependence on caregivers
Harmatz et al, Mol Genet Metab, 2013; Hendriksz et al, J Inherit Metab Dis, 2012; Montano et al, J Inherit Metab Dis, 2007
Maximizing functional capacity
is the key to optimizing quality of life
Optimizing the functional status of major organ
systems and, consequently, the quality of life of
Morquio A patients requires:
multidisciplinary management
regular assessments
timely interventions
timely post-operative rehabilitation
Endurance testing assesses functional capacity
Endurance tests measure the efficiency of performing a task and provide
assessments of:
Functional status of the cardiac, respiratory and musculoskeletal systems
Overall disease progression
Quality of life
Response to treatments
McDonald et al, J Pediatr Rehabil Med, 2010; Hendriksz et al, J Inherit Metab Dis, 2012
Submaximal intensity tests are sensitive
indicators of endurance for MPS patients
Recommended endurance tests for assessing submaximal
functional capacity in Morquio A patients include:
6 minute walk test (6MWT)
measures how far a person can walk on a hard, flat
surface in 6 minutes
a standardized test (American Thoracic Society, 2002)
used to assess endurance in patients with MPS VI
(Harmatz et al, 2005) and Morquio A (Harmatz et al, 2013)
Image courtesy of Elizabeth Wright
3 minute stair climb (3MSCT)
measures how many steps a person can ascend in 3
minutes, using rails and resting as needed
used to assess edurance in patients with MPS VI (Harmatz
et al, 2005) and Morquio A (Harmatz et al, 2013)
Harmatz et al, Mol Genet Metab, 2013; Harmatz et al, Pediatrics, 2005; McDonald et al, J Pediatr Rehabil Med, 2010;
Hendriksz et al, J Inherit Metab Dis, 2012
Regular assessments are recommended
for optimal patient quality of life
At
diagnosis
Annually
As clinically
indicated
Evaluation by physiotherapist
X
X
X
6 MWT (if physically and developmentally able)
X
X
X
3 MSCT (if physically and developmentally able)
X
X
X
Assessment
Hendriksz et al, J Inherit Metab Dis, 2012

similar documents