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