Background
MPS Type | Main clinical features | Enzyme deficient | Substrate accumulated |
---|---|---|---|
Skeletal disease, soft tissue storage and a range of central nervous system disease
| |||
I-H Hurler | Developmental delay, coarse facial features, dysostosis multiplex, hepatosplenomegaly, death by age 10 years | Alpha-L-iduronidase | Heparan sulfate |
I-HS Hurler-Scheie | Micrognathia, toe walking, moderate coarse facies, possible normal intelligence, death by 20s (phenotype intermediate between I-H and I-HS) | Dermatan sulfate | |
I-S Scheie | Aortic valve disease, joint disease, corneal clouding, normal facies, survive into adulthood | ||
II Hunter | Severe: Disease course similar to MPS I-H, but clear corneas, aggressive behaviour and developmental delay | Iduronate sulfatase | Heparan sulfate |
Mild: Normal or near-normal intelligence, less pronounced physical features | Dermatan sulfate | ||
MPS VII Sly | Variable intermediate presentation similar to MPS I, from fetal hydrops to mild dysmorphism; dense inclusions in granulocytes | Beta-glucuronidase | Heparan sulfate |
Dermatan sulfate | |||
MPS VI Maroteaux-Lamy | Similar to MPS I without CNS disease, pachymeningitis cervicalis, death in teens and 20s; Hurler phenotype with marked corneal clouding; mild, moderate and severe expression in different families | N-acetylgalactosamine-4-sulfatase (arylsulfatase B) | Dermatan sulfate |
Skeletal, cartilage and ligament disease primarily
| |||
MPS IVA Morquio A | Skeletal disease (bone dysplasia) with short stature, ligamentous laxity, corneal opacities, final height <125 cm | N-acetylgalactosamine-6-sulfatase | Keratan sulfate |
MPS IVB Morquio B | Same as IV-A but milder; adult height >120 cm | Beta-galactosidase | |
MPS IX Natowicz syndrome | Periarticular masses, nodular synovium, popliteal cyst, large joint effusion | Hyaluronidase 1 | Hyaluronan |
MPS IIIA Sanfilippo A | Behavioural problems, sleeping disorder, aggression, progressive dementia, mild dysmorphism, coarse hair, clear corneas, survival to adulthood possible | Sulfamidase | Heparan sulfate |
MPS IIIB Sanfilippo B | Alpha-N-acteylglucosaminidase | ||
MPS IIIC Sanfilippo C | GAC-acteylase | ||
MPS IIID Sanfilippo D | N-acetylglucosamine-6-sulfatase |
Methods
Results and discussion
Manoeuvre tested | pGALS instruction | All MPS (n = 18 patients) 1203 total observations | MPS I (n = 13) | MPS II (n = 4) | Mannosidosis (n = 1) |
---|---|---|---|---|---|
Shoulder abduction, external rotation
|
Hands behind neck
| 49/54 (91%) | 35/39 (90%) | 12/12 (100%) | 2/3 (67%) |
Shoulder flexion
|
Reach arms up
| 48/54 (89%) | 36/39 (93%) | 12/12 (100%) | 0/3 (0%) |
Wrist flexion
|
Hands together back to back
| 41/54 (76%) | 27/39 (69%) | 12/12 (100%) | 2/3 (67%) |
Elbow extension
| Reach up | 39/53 (74%) | 26/39 (90%) | 12/12 (100%) | 1/2 (50%) |
TMJ excursion
| Open mouth wide and try to put 3 fingers inside | 39/54 (72%) | 28/39 (72%) | 10/12 (83%) | 1/3 (33%) |
MCP, DIP, PIP extension
| Hands and wrists together | 37/54 (69%) | 24/39 (62%) | 11/12 (92%) | 2/3 (67%) |
Forward flexion of spine
| Bend forwards. Observe curvature of spine from all sides | 31/50 (62%) | 21/35 (60%) | 8/12 (67%) | 2/3 (67%) |
Spinal deformity
| Observe patient standing and then bending forwards | 28/45 (62%) | 22/34 (65%) | 5/9 (56%) | 1/2 (50%) |
Gait
| Observe patient walking | 28/45 (62%) | 20/32 (63%) | 7/10 (70%) | 1/3 (33%) |
Wrist extension
| Hands palm to palm | 33/53 (60%) | 22/39 (56%) | 11/11 (100%) | 0/3 (0%) |
MCP/DIP/PIP extension
| Hands out in front | 29/52 (56%) | 17/37 (46%) | 12/12 (100%) | 0/3 (0%) |
Cervical spine lateral flexion
| Touch ear to shoulder | 29/53 (55%) | 17/38 (45%) | 12/12 (100%) | 0/3 (0%) |
Elbow extension
| Hands out in front | 22/40 (55%) | 12/27 (44%) | 9/11 (82%) | 1/2 (50%) |
Ankle dorsiflexion
| Walk on heels | 24/45 (53%) | 15/33 (45%) | 7/9 (78%) | 2/3 (67%) |
Neck extension
| Look up to the ceiling | 28/53 (53%) | 19/38 (50%) | 9/12 (75%) | 0/3 (0%) |
Forearm supination
| Turn hand over | 20/42 (48%) | 10/30 (33%) | 9/11 (82%) | 1/1 (100%) |
Opposition of thumb and 3
rd
-5
th
fingers
| Touch tips of fingers with thumb | 23/54 (43%) | 14/39 (36%) | 8/12 (67%) | 1/3 (33%) |
MCP/DIP/PIP flexion
| Make a fist | 20/54 (37%) | 10/39 (26%) | 10/12 (83%) | 0/3 (0%) |
Elbow flexion
| Put hands behind neck | 12/42 (29%) | 6/27 (33%) | 5/12 (42%) | 1/3 (33%) |
Knee extension
| Bring ankle up to bottom | 12/44 (27%) | 7/29 (24%) | 4/12 (33%) | 1/3 (33%) |
Knee flexion
| 11/45 (24%) | 4/30 (13%) | 7/12 (58%) | 0/3 (0%) | |
Opposition of thumb and index finger
| Touch tip of finger with thumb | 10/54 (19%) | 5/39 (13%) | 5/12 (42%) | 0/3 (0%) |
Elbow flexion
| Put hands and wrists together | 7/53 (13%) | 5/39 (13%) | 2/11 (18%) | 0/3 (0%) |
Ankle plantar flexion
| Walk on tip-toes | 4/45 (9%) | 2/33 (6%) | 2/9 (22%) | 0/3 (0%) |
Manoeuvre tested | pGALS instruction | MPS I (Hurler) (n = 5) |
---|---|---|
Spinal deformity
| 15/15 (100%) | |
Shoulder flexion
| Reach arms up | 13/15 (87%) |
TMJ excursion
| Open mouth wide and try to put 3 fingers inside | 13/15 (87%) |
Forward flexion of spine
| Bend forwards. Observe curvature of spine from all sides | 11/15 (73%) |
Shoulder abduction, external rotation
| Hands behind neck | 11/15 (73%) |
Wrist flexion
| Hands together back to back | 10/15 (67%) |
Elbow extension
| Reach up | 9/15 (60%) |
Gait
| Observe patient walking | 9/15 (60%) |
MCP, DIP, PIP extension
| Hands and wrists together | 8/15 (53%) |
Neck extension
| Look up to the ceiling | 7/15 (47%) |
Wrist extension
| Hands palm to palm | 6/15 (40%) |
MCP/DIP/PIP extension
| Hands out in front | 6/15 (40%) |
Ankle dorsiflexion
| Walk on heels | 6/15 (40%) |
Elbow extension
| Hands out in front | 4/11 (36%) |
Cervical spine lateral flexion
| Touch ear to shoulder | 5/15 (33%) |
Forearm supination
| Turn hand over | 4/12 (33%) |
Opposition of thumb and 3
rd
-5
th
fingers
| Touch tips of fingers with thumb | 4/15 (27%) |
Knee extension
| Bring ankle up to bottom | 2/14 (14%) |
Knee flexion
| 1/15 (7%) | |
Elbow flexion
| Put hands behind neck | 1/15 (7%) |
Elbow flexion
| Put hands and wrists together | 1/15 (7%) |
Ankle plantar flexion
| Walk on tip-toes | 0/15 (0%) |
MCP/DIP/PIP flexion
| Make a fist | 0/15 (0%) |
Opposition of thumb and index finger
| Touch tip of finger with thumb | 0/15 (0%) |
Manoeuvre tested | pGALS instruction | MPS Ia (n = 8) |
---|---|---|
Shoulder abduction, external rotation
| Hands behind neck | 24/24 (100%) |
Shoulder flexion
| Reach arms up | 23/24 (96%) |
Elbow extension
| Reach up | 17/24 (71%) |
Wrist flexion
| Hands together back to back | 17/24 (71%) |
Wrist extension
| Hands palm to palm | 16/24 (67%) |
MCP, DIP, PIP extension
| Hands and wrists together | 16/24 (67%) |
Gait
| Observe patient walking | 11/17 (65%) |
TMJ excursion
| Open mouth wide and try to put 3 fingers inside | 15/24 (62%) |
Spinal deformity
| 7/19 (56%) | |
Forward flexion of spine
| Bend forwards. Observe curvature of spine from all sides | 10/19 (53%) |
Neck extension
| Look up to the ceiling | 12/23 (52%) |
Cervical spine lateral flexion
| Touch ear to shoulder | 12/23 (52%) |
MCP/DIP/PIP extension
| Hands out in front | 11/22 (50%) |
Elbow extension
| Hands out in front | 8/16 (50%) |
Ankle dorsiflexion
| Walk on heels | 9/18 (50%) |
MCP/DIP/PIP flexion
| Make a fist | 10/24 (42%) |
Opposition of thumb and 3
rd
-5
th
fingers
| Touch tips of fingers with thumb | 10/24 (42%) |
Elbow flexion
| Put hands behind neck | 5/12 (42%) |
Forearm supination
| Turn hand over | 6/18 (33%) |
Knee extension
| Bring ankle up to bottom | 5/15 (33%) |
Knee flexion
| 3/15 (20%) | |
Opposition of thumb and index finger
| Touch tip of finger with thumb | 5/24 (21%) |
Elbow flexion
| Put hands and wrists together | 4/24 (17%) |
Ankle plantar flexion
| Walk on tip-toes | 2/18 (11%) |
Manoeuvre tested | pGALS instruction | MPS II (n = 4) |
---|---|---|
Shoulder flexion
| Reach arms up | 12/12 (100%) |
Shoulder abduction, external rotation
| Hands behind neck | 12/12 (100%) |
Elbow extension
| Reach up | 12/12 (100%) |
Wrist flexion
| Hands together back to back | 12/12 (100%) |
Wrist extension
| Hands palm to palm | 11/11 (100%) |
MCP/DIP/PIP extension
| Hands out in front | 12/12 (100%) |
Cervical spine lateral flexion
| Touch ear to shoulder | 12/12 (100%) |
MCP, DIP, PIP extension
| Hands and wrists together | 11/12 (92%) |
TMJ excursion
| Open mouth wide and try to put 3 fingers inside | 10/12 (83%) |
MCP/DIP/PIP flexion
| Make a fist | 10/12 (83%) |
Elbow extension
| Hands out in front | 9/11 (82%) |
Forearm supination
| Turn hand over | 9/11 (82%) |
Ankle dorsiflexion
| Walk on heels | 7/9 (78%) |
Neck extension
| Look up to the ceiling | 9/12 (75%) |
Gait
| Observe patient walking | 7/10 (70%) |
Forward flexion of spine
| Bend forwards. Observe curvature of spine from all sides. | 8/12 (67%) |
Opposition of thumb and 3
rd
-5
th
fingers
| Touch tips of fingers with thumb | 8/12 (67%) |
Spinal deformity
| 5/9 (56%) | |
Opposition of thumb and index finger
| Touch tip of finger with thumb | 5/12 (42%) |
Elbow flexion
| Put hands behind neck | 5/12 (42%) |
Knee extension
| Bring ankle up to bottom | 4/12 (33%) |
Knee flexion
| 7/12 (58%) | |
Ankle plantar flexion
| Walk on tip-toes | 2/9 (22%) |
Elbow flexion
| Put hands and wrists together | 2/11 (18%) |