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 3 yr 7 yr 14 yr 18 yr 26 yr 4 yr 10 yr 16 yr 17 yr 28 yr 30 yr

Morquio A disease process leads to progressive multisystemic manifestations

Patients typically require surgery

30% 25% 20% 15% 10% 5% 0% 25,5% 22,2% 20,1% 18,5% 17,5% 10,8% 9,2% 5,5%

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

220 215 210 205 200 195 190 185 180 218 193,1 Age ≤ 18 years n=248 Age > 18 years n=68 212,6 All n=316

Mean 3MSCT

15 10 5 0 35 30 25 20 31,6 24,1 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)

30 All n=274

MorCAP baseline data

Harmatz et al,

Mol Genet Metab

, 2013

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 Assessment

Evaluation by physiotherapist 6 MWT (if physically and developmentally able) 3 MSCT (if physically and developmentally able)

At diagnosis Annually As clinically indicated

X X X X X X X X X Hendriksz et al,

J Inherit Metab Dis

, 2012