Download - Morquio A: Burden of disease
Morquio A: Burden of disease
Clinical manifestations:Skeletal dysplasia Short statureCervical spine instabilitySpinal cord compression Impaired enduranceRespiratory diseaseHearing lossCorneal cloudingHeart valvular diseaseDental abnormalitiesNormal intelligence
Morquio A is a multisystemic disorder
Morquio A is progressive
18 yr3 mo 14 yr3 yr 7 yr 26 yr
17 yr16 yr4 yr 30 yr10 yr 28 yr
Morquio A disease process leads to progressive multisystemic manifestations
Patients typically require surgery
> 70% of 325 Morquio A subjects had at least one surgical procedure
Harmatz et al, Mol Genet Metab, 2013
0%
5%
10%
15%
20%
25%
30%
25.5%
22.2%20.1%
18.5%17.5%
10.8%9.2%
5.5%
% S
ubje
cts
MorCAP baseline data
n = 325 Morquio A subjects (mean age= 14.5 years) Data based on medical history reviews
Harmatz et al, Mol Genet Metab, 2013; Montano et al, J Inherit Metab Dis, 2007
Mobility is compromised
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)
Use of wheelchairs and walking aids is common
Aslam et al, JIMD Rep, 2013; Harmatz et al, Mol Genet Metab, 2013; BioMarin data on file
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
Mean 6MWT Mean 3MSCT
n=248 n=68 n=316 n=215 n=59 n=274Age ≤ 18 years Age > 18 years All
180
185
190
195
200
205
210
215
220 218
193.1
212.6
m
Age ≤ 18 years Age > 18 years All 0
5
10
15
20
25
30
3531.6
24.1
30
Ste
ps/m
inMean 6MWT = 212.6 ±152.2 m (n = 316
subjects) Mean 3MSCT = 30.0 ±24.0 stairs (n= 274
subjects)
Harmatz et al, Mol Genet Metab, 2013MorCAP baseline data
Endurance is impaired
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
Patient quality of life declines with disease progression
In Morquio A, patient quality of life is compromised by:
Optimizing the functional status of major organ systems and, consequently, the quality of life of Morquio A patients requires:
multidisciplinary managementregular assessmentstimely interventionstimely post-operative rehabilitation
Maximizing functional capacity is the key to optimizing quality of life
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 systemsOverall disease progressionQuality of lifeResponse to treatments
McDonald et al, J Pediatr Rehabil Med, 2010; Hendriksz et al, J Inherit Metab Dis, 2012
Image courtesy of Elizabeth Wright
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)
3 minute stair climb (3MSCT) measures how many steps a person can ascend in 3 minutes, using rails and resting as neededused 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
Submaximal intensity tests are sensitive indicators of endurance for MPS patients
Assessment 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
Regular assessments are recommended for optimal patient quality of life
Hendriksz et al, J Inherit Metab Dis, 2012