MUCOPOLYSACCHARIDOSES
Lysosomal Storage Disorders | Dysostosis Multiplex | Spinal Instability
MPS CLASSIFICATION BY DEFICIENT ENZYME
Critical Must-Knows
- Dysostosis multiplex - pathognomonic radiographic pattern: J-shaped sella, paddle ribs, anterior vertebral beaking, bullet-shaped metacarpals
- Cervical instability - atlantoaxial subluxation due to odontoid hypoplasia, most severe in MPS IV (Morquio)
- Anaesthetic risks - difficult airway, atlantoaxial instability, restrictive lung disease require specialist input
- MPS IV (Morquio) - unique because intelligence is PRESERVED but skeletal manifestations most severe
- Enzyme replacement therapy - available for MPS I, II, IVA, VI but does NOT cross blood-brain barrier
Examiner's Pearls
- "MPS IV (Morquio) has NORMAL intelligence but most severe skeletal disease
- "Odontoid hypoplasia causes atlantoaxial instability - high anaesthetic risk
- "Carpal tunnel syndrome common in MPS - often first presenting sign in adults
- "HSCT must be done before age 2 for cognitive benefit in MPS I
Critical MPS Examination Points
Cervical Spine Emergency
All MPS patients have potential atlantoaxial instability due to odontoid hypoplasia and ligamentous laxity. ALWAYS assess cervical spine before any procedure. Flexion-extension views required. High anaesthetic mortality without precautions.
Airway Difficulties
Difficult intubation due to: short neck, large tongue, mandibular hypoplasia, tonsillar hypertrophy, tracheal narrowing from GAG deposition. Require experienced paediatric anaesthetist and fibreoptic intubation available.
Morquio Syndrome (MPS IV)
Only MPS with normal intelligence but most severe skeletal manifestations. Universal odontoid hypoplasia (50% symptomatic cord compression), severe genu valgum, thoracolumbar kyphosis. Major surgical candidate.
Dysostosis Multiplex
Classic radiographic pattern in all MPS types: J-shaped sella turcica, paddle ribs, anterior vertebral beaking, proximal metacarpal pointing, flared iliac wings. First thing to look for on X-rays.
At a Glance
Mucopolysaccharidoses (MPS) are lysosomal storage disorders with glycosaminoglycan accumulation causing progressive skeletal abnormalities. The hallmark radiographic pattern is dysostosis multiplex: J-shaped sella, paddle ribs, anterior vertebral beaking, and bullet-shaped metacarpals. MPS IV (Morquio syndrome) is unique—normal intelligence but most severe skeletal disease, with 50% having symptomatic atlantoaxial instability due to odontoid hypoplasia. All MPS patients carry significant anaesthetic risks (difficult airway, cervical instability, restrictive lung disease). Enzyme replacement therapy is available for MPS I, II, IVA, and VI but does not cross the blood-brain barrier; HSCT must be performed before age 2 for cognitive benefit in MPS I.
MPS Types by Features - HHMMSS
Memory Hook:HHMMSS - like counting seconds, count the MPS types. Double letters for the key ones
Dysostosis Multiplex X-ray Features - JARS PB
Memory Hook:JARS PB - GAGs stored in JARS cause PB (peanut butter) thick bones
Orthopaedic MPS Complications - STICK
Memory Hook:Things STICK in MPS - GAGs stick in tissues causing all these problems
Overview and Epidemiology
The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficiency of enzymes required for the degradation of glycosaminoglycans (GAGs), formerly called mucopolysaccharides. Accumulation of GAGs in tissues leads to progressive multisystem disease with prominent skeletal manifestations. [1]
Pathophysiology: GAGs are complex carbohydrates that form essential components of connective tissue matrix, including dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate. In MPS, deficient lysosomal enzymes cannot break down specific GAGs, leading to accumulation in lysosomes. This causes cellular dysfunction, inflammation, and progressive tissue damage. [2]
Epidemiology: The combined incidence of all MPS types is approximately 1:25,000 live births, though this varies by population and type. [1,3]
Individual MPS Incidence (approximate):
- MPS I (Hurler/Scheie): 1:100,000
- MPS II (Hunter): 1:100,000-150,000 (X-linked, males only)
- MPS III (Sanfilippo): 1:70,000 (most common)
- MPS IV (Morquio): 1:75,000-100,000
- MPS VI (Maroteaux-Lamy): 1:250,000
- MPS VII (Sly): Very rare, fewer than 1:250,000
Australian Newborn Screening
Some Australian states now include MPS I in newborn screening programs. Early diagnosis enables HSCT before irreversible neurological damage occurs. The critical window for transplantation is before age 2 years for cognitive benefit.
Pathophysiology and Genetics
Glycosaminoglycan Metabolism: Glycosaminoglycans are long, unbranched polysaccharide chains composed of repeating disaccharide units. They are attached to core proteins to form proteoglycans, which are essential components of extracellular matrix, particularly in cartilage, bone, and connective tissue.
The Four Main GAGs:
| GAG Type | Location | MPS Types Affected |
|---|---|---|
| Dermatan sulfate | Skin, blood vessels, heart valves | MPS I, II, VI, VII |
| Heparan sulfate | CNS, liver, retina | MPS I, II, III, VII |
| Keratan sulfate | Cornea, cartilage, intervertebral discs | MPS IV |
| Chondroitin sulfate | Cartilage, bone, heart | MPS VII |
Pathogenesis of Skeletal Disease:
- Chondrocyte dysfunction - GAG accumulation impairs normal chondrocyte maturation
- Growth plate disorganization - disrupted columnar arrangement reduces longitudinal growth
- Abnormal endochondral ossification - leads to short stature and limb deformities
- Bone matrix abnormalities - irregular mineralization causes osteopenia
- Ligamentous laxity - accumulated GAGs weaken collagen cross-linking
Cervical Spine Instability Mechanism
In MPS, odontoid hypoplasia results from defective endochondral ossification. Combined with ligamentous laxity from GAG accumulation in periarticular tissues, this creates atlantoaxial instability. The posterior arch of C1 moves anteriorly relative to C2, compressing the cervical cord. This is most severe in MPS IV (Morquio syndrome).
Inheritance Patterns:
- Autosomal recessive: MPS I, III, IV, VI, VII (all except Hunter)
- X-linked recessive: MPS II (Hunter syndrome) - males affected, females are carriers
Genetic Counseling Implications: For autosomal recessive MPS, carrier parents have a 25% risk of affected offspring with each pregnancy. Prenatal diagnosis is available via CVS or amniocentesis for all MPS types. Preimplantation genetic diagnosis is an option for affected families.
Classification
Classification by Enzyme Deficiency:
| MPS Type | Eponym | Deficient Enzyme | GAG Stored | Intelligence | Key Features |
|---|---|---|---|---|---|
| I-H | Hurler | Alpha-L-iduronidase | DS, HS | Impaired | Most severe, death by 10y |
| I-S | Scheie | Alpha-L-iduronidase | DS, HS | Normal | Mildest, normal lifespan |
| I-H/S | Hurler-Scheie | Alpha-L-iduronidase | DS, HS | Variable | Intermediate phenotype |
| II | Hunter | Iduronate-2-sulfatase | DS, HS | Variable | X-linked, no corneal clouding |
| III A-D | Sanfilippo | Various | HS | Severely impaired | Severe CNS, mild skeletal |
| IV A | Morquio A | GALNS | KS, CS | Normal | Most severe skeletal disease |
| IV B | Morquio B | Beta-galactosidase | KS | Normal | Milder than IVA |
| VI | Maroteaux-Lamy | Arylsulfatase B | DS | Normal | Corneal clouding, cardiac |
| VII | Sly | Beta-glucuronidase | DS, HS, CS | Variable | Very rare, hydrops fetalis |
DS = dermatan sulfate; HS = heparan sulfate; KS = keratan sulfate; CS = chondroitin sulfate
Clinical Presentation
Age of Presentation: Presentation age correlates with disease severity:
- Severe MPS I (Hurler): First year of life - hepatosplenomegaly, developmental delay
- Intermediate types: 2-6 years - coarse facies, joint stiffness, hernias
- Attenuated types: Childhood-adulthood - carpal tunnel, joint problems, cardiac
General Clinical Features (Common to Most MPS):
Craniofacial:
- Coarse facies (gargoylism) - thickened features, broad nose, thick lips
- Macrocephaly with frontal bossing
- Corneal clouding (NOT in Hunter syndrome)
- Chronic rhinorrhea and otitis media
- Hearing loss (conductive and sensorineural)
Neurological:
- Cognitive impairment (not in MPS IV, VI, some II)
- Communicating hydrocephalus
- Spinal cord compression (cervical, thoracolumbar)
- Carpal tunnel syndrome
Cardiac:
- Valve thickening and regurgitation
- Coronary artery disease
- Cardiomyopathy
Respiratory:
- Restrictive lung disease
- Obstructive sleep apnea
- Tracheobronchomalacia
Pre-Operative Assessment Checklist
Before ANY procedure in MPS patients:
- Cervical spine - flexion-extension X-rays, MRI if symptoms
- Cardiac - echocardiogram (valve disease, cardiomyopathy)
- Respiratory - pulmonary function tests, sleep study if snoring
- Airway - ENT assessment, fibreoptic equipment available
- Anaesthesia - experienced paediatric/specialist anaesthetist
Orthopaedic Features by Region:
Cervical Spine:
- Odontoid hypoplasia (universal in MPS IV, common in others)
- Atlantoaxial instability
- Cervical stenosis
- Gibbus deformity at craniocervical junction
Thoracolumbar Spine:
- Kyphosis/kyphoscoliosis
- Thoracolumbar gibbus (L1/L2 vertebral hypoplasia)
- Spinal stenosis
Upper Limb:
- Carpal tunnel syndrome (common, often bilateral)
- Trigger fingers
- Joint stiffness and contractures
- Claw hand deformity
- Restricted shoulder motion
Lower Limb:
- Genu valgum (especially MPS IV)
- Hip dysplasia and coxa valga
- Pes planus
- Ankle valgus
Hands:
- Bullet-shaped or pointed proximal metacarpals (radiographic)
- Short, broad hands
- Contractures (except MPS IV which has laxity)
Investigations
Screening and Diagnostic Tests:
Urine GAG Analysis:
- Initial screening test
- Quantitative total GAG and qualitative GAG pattern
- Elevated in most MPS, but can be normal in attenuated forms
- Pattern suggests MPS type (dermatan, heparan, keratan sulfate)
Enzyme Assay:
- Gold standard for diagnosis
- Performed on leukocytes, fibroblasts, or dried blood spots
- Each MPS type has specific enzyme deficiency
- Confirms diagnosis and allows carrier testing
Genetic Testing:
- Identifies specific mutations
- Enables prenatal diagnosis and family screening
- Genotype-phenotype correlation possible for some types
Radiographic Assessment - Dysostosis Multiplex:
Dysostosis Multiplex Features by Region
| Region | Radiographic Finding | Clinical Significance |
|---|---|---|
| Skull | J-shaped sella turcica, thick calvarium | Hydrocephalus risk, increased ICP |
| Spine | Anterior vertebral beaking (inferior), platyspondyly | Kyphosis, gibbus deformity |
| Ribs | Paddle or oar-shaped (widened anteriorly) | Restrictive lung disease |
| Pelvis | Flared iliac wings, shallow acetabulum | Hip dysplasia, subluxation risk |
| Long bones | Widened diaphyses, coarse trabeculation | Fracture risk, deformity |
| Hands | Bullet-shaped proximal metacarpals | Pathognomonic finding |
Cervical Spine Imaging Protocol:
Plain Radiographs:
- Lateral (neutral, flexion, extension)
- AP and open mouth odontoid views
- Measure atlantodental interval (ADI): greater than 5mm concerning in children
MRI Cervical Spine:
- Gold standard for cord compression assessment
- Indicated if ADI greater than 5mm or neurological symptoms
- Shows soft tissue GAG deposition causing stenosis
CT Cervical Spine:
- Best for bony anatomy - odontoid hypoplasia, os odontoideum
- 3D reconstructions helpful for surgical planning
Cervical Instability Assessment
Key measurements in MPS cervical spine assessment:
- Atlantodental interval (ADI): Normal less than 3mm adult, less than 5mm child. Greater than 5mm indicates instability.
- Space available for cord (SAC): Measured from posterior C1 ring to anterior C2 body. Less than 14mm indicates significant stenosis.
- Powers ratio: BC/OA. Greater than 1.0 indicates anterior atlantoaxial subluxation.
Additional Investigations:
| Investigation | Indication | Key Findings |
|---|---|---|
| Echocardiogram | All MPS patients | Valve thickening, regurgitation |
| Sleep study | Snoring, apnea | Obstructive sleep apnea |
| PFTs | Preoperative | Restrictive pattern |
| Nerve conduction | Numbness, weakness | Carpal tunnel syndrome |
| Audiometry | All patients | Conductive/sensorineural loss |
| Ophthalmology | Visual symptoms | Corneal clouding, retinopathy |
Management
Disease-Modifying Therapies:
1. Enzyme Replacement Therapy (ERT): Available for MPS I, II, IVA, VI
| MPS Type | Enzyme | Brand Name | Dosing | Limitations |
|---|---|---|---|---|
| MPS I | Laronidase | Aldurazyme | 0.58 mg/kg weekly IV | Does not cross BBB |
| MPS II | Idursulfase | Elaprase | 0.5 mg/kg weekly IV | Does not cross BBB |
| MPS IVA | Elosulfase alfa | Vimizim | 2 mg/kg weekly IV | Primarily skeletal benefit |
| MPS VI | Galsulfase | Naglazyme | 1 mg/kg weekly IV | Significant antibody formation |
ERT Outcomes:
- Improves respiratory function and endurance
- Reduces hepatosplenomegaly
- Some improvement in cardiac function
- Does NOT reverse established skeletal disease
- Does NOT cross blood-brain barrier (no cognitive benefit)
2. Haematopoietic Stem Cell Transplant (HSCT):
- Only treatment to halt cognitive decline in MPS I
- Most effective if performed before age 2 years
- Donor-derived enzyme crosses BBB
- Carries significant transplant-related mortality (10-15%)
- Standard of care for severe MPS I (Hurler)
HSCT Timing
For MPS I (Hurler), HSCT should be performed before age 2 years and ideally before DQ falls below 70. After age 2, irreversible neurological damage limits benefit. Australian practice follows international guidelines recommending early HSCT with busulfan-based conditioning.
3. Substrate Reduction Therapy:
- Genistein (isoflavone) reduces GAG synthesis
- Investigational, may have role as adjunct therapy
4. Gene Therapy:
- Currently in clinical trials for several MPS types
- Potential for single-treatment disease modification
- AAV-mediated liver-directed therapy most advanced
Supportive Medical Care:
- ENT: Adenotonsillectomy for airway obstruction
- Respiratory: CPAP/BiPAP for sleep apnea
- Cardiac: Valve surgery if severe regurgitation
- Ophthalmology: Corneal transplant if severe clouding
Multidisciplinary care coordination is essential for optimal outcomes in MPS patients.
Complications
Cervical Myelopathy:
- Most serious orthopaedic complication
- Results from atlantoaxial instability and/or stenosis
- Presents with weakness, hyperreflexia, gait disturbance
- May be sudden (trauma) or insidious
- Requires urgent surgical decompression and fusion
Anaesthetic Complications:
| Complication | Mechanism | Prevention |
|---|---|---|
| Difficult intubation | Macroglossia, short neck, mandibular hypoplasia | Fibreoptic intubation, awake technique |
| Cervical cord injury | Atlantoaxial instability during positioning | Preoperative imaging, in-line stabilization, halo |
| Respiratory failure | Restrictive lung disease, tracheal narrowing | Preoperative PFTs, postoperative ICU |
| Cardiac events | Valve disease, cardiomyopathy | Preoperative echo, cardiac optimization |
Surgical Complications:
Spinal Surgery:
- Nonunion/pseudarthrosis (higher in poor bone quality)
- Hardware failure
- Neurological deterioration (positioning, decompression)
- Adjacent segment degeneration
Lower Limb Surgery:
- Recurrence of deformity (especially genu valgum)
- Hardware prominence
- Wound healing issues
- Need for repeat procedures
Upper Limb:
- Carpal tunnel recurrence
- Incomplete release
- Trigger finger recurrence
Disease Progression Despite Treatment:
- ERT does not reverse established skeletal disease
- Skeletal manifestations continue to progress
- Multiple surgical procedures often required throughout life
- Mobility decline despite intervention
Mortality and Morbidity
Leading causes of death in MPS:
- Respiratory failure - restrictive lung disease, sleep apnea, recurrent infections
- Cardiac failure - valve disease, cardiomyopathy
- Cervical myelopathy - sudden death from cord compression Early ERT/HSCT and proactive orthopaedic management have improved survival but do not fully normalize life expectancy.
Outcomes and Prognosis
Natural History Without Treatment:
| MPS Type | Untreated Life Expectancy | Major Causes of Death |
|---|---|---|
| MPS I (Hurler) | 10-15 years | Cardiac, respiratory |
| MPS I (Scheie) | Normal | Cardiac complications |
| MPS II (severe) | 15-25 years | Respiratory, cardiac |
| MPS III | 15-30 years | Neurological decline |
| MPS IV | 20-40 years | Cervical myelopathy, respiratory |
| MPS VI | 20-40 years | Cardiac, respiratory |
Impact of Disease-Modifying Therapy:
HSCT for MPS I:
- Survival greater than 90% with current protocols
- Cognitive stabilization if transplanted early (before age 2)
- Somatic disease continues to progress (skeletal, cardiac)
- 10-15 year post-transplant data shows improved survival
ERT Outcomes:
- 6-minute walk test improvement
- Reduced hepatosplenomegaly
- Some pulmonary function improvement
- Limited skeletal benefit - does not reverse deformity
Surgical Outcomes:
Cervical Fusion:
- High fusion rates (greater than 90%) but technical challenges
- Neurological stabilization in most
- Revision rates 10-20% for hardware issues
Genu Valgum Correction:
- Guided growth effective but recurrence common
- Osteotomy provides definitive correction at maturity
- Improves ambulation and quality of life
Carpal Tunnel Release:
- Good outcomes, symptom relief in 90%
- Recurrence rate 5-10%
Multidisciplinary Care Impact:
- Specialized MPS clinics improve outcomes
- Coordinated medical, surgical, and supportive care
- Regular surveillance prevents complications
- Australian centres: Sydney Children's Hospital, Royal Children's Melbourne
Evidence Base
Enzyme Replacement Therapy for MPS IVA
- 6-minute walk test improved by 22.5m vs placebo at 24 weeks
- Urinary keratan sulfate reduced by 40%
- Side effects mainly infusion-related reactions
- Now standard of care for MPS IVA
HSCT for MPS I (Hurler)
- 5-year survival 74% overall, 95% in those surviving first year
- Cognitive benefit requires transplant before age 2
- Best outcomes with DQ greater than 70 at transplant
- Skeletal and cardiac disease continue to progress despite HSCT
Cervical Spine Surgery in MPS
- Fusion rate 87% in MPS patients
- Neurological improvement in 70% of myelopathy patients
- Complication rate 26% but no perioperative mortality
- Early intervention before fixed deficit improves outcomes
Genu Valgum Management in MPS IV
- Guided growth effective but 40% recurrence rate
- Osteotomy at skeletal maturity provides definitive correction
- Combined approach recommended: guided growth then osteotomy
- Most patients require multiple procedures
MPS IVA Natural History Study
- Mean survival 25 years in natural history
- Cervical instability in 50% of patients
- Genu valgum universal (100%)
- Respiratory compromise in 60%
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: MPS IV with Cervical Myelopathy
"A 12-year-old boy with Morquio syndrome (MPS IV) presents with progressive leg weakness over 6 months. He has a shuffling gait and increased tone in both legs with upgoing plantars. How would you assess and manage this patient?"
Scenario 2: New Diagnosis of MPS with Skeletal Features
"A 3-year-old child is referred by a paediatrician with a new diagnosis of MPS I (Hurler syndrome). They want orthopaedic input on the skeletal manifestations. What are the key orthopaedic concerns and how would you structure management?"
Scenario 3: Progressive Genu Valgum
"An 8-year-old girl with MPS IV (Morquio syndrome) is referred with progressive knock-knees. Mechanical axis shows 20 degrees of valgus bilaterally with the deformity predominantly at the distal femur. She is ambulatory but fatigues quickly. How would you manage this?"
Scenario 4: Carpal Tunnel in Young Adult with MPS
"A 25-year-old man with MPS II (Hunter syndrome, attenuated type) presents with bilateral hand weakness. He works in IT and has noticed difficulty typing. He has normal intelligence and was diagnosed at age 15. Nerve conduction studies show severe bilateral carpal tunnel syndrome. How would you manage this?"
MCQ Practice Points
Q: Which MPS type has normal intelligence but the most severe skeletal disease?
A: MPS IV (Morquio syndrome). This is because keratan sulfate (the stored GAG in Morquio) is predominantly found in cartilage, not brain tissue. These patients have universal odontoid hypoplasia and severe genu valgum but can participate fully in surgical decision-making.
Q: Which is the ONLY X-linked mucopolysaccharidosis?
A: MPS II (Hunter syndrome). All other MPS types are autosomal recessive. Hunter syndrome also uniquely does NOT have corneal clouding, distinguishing it from other MPS types.
Q: What are the key features of dysostosis multiplex on X-ray?
A: JARS PB mnemonic: J-shaped sella turcica, Anterior vertebral beaking, Ribs paddle-shaped, Short metacarpals with proximal pointing, Pelvis with flared iliac wings, Bones with widened diaphyses.
Q: When must HSCT be performed for cognitive benefit in MPS I?
A: Before age 2 years. Transplantation after this age will not halt or reverse cognitive decline because irreversible neurological damage has already occurred. The critical window is ideally before DQ falls below 70.
Q: Why does ERT not help established skeletal disease?
A: ERT does not cross the blood-brain barrier and cannot reach already-formed skeletal tissue with established GAG deposits. It can prevent further accumulation but cannot reverse existing damage. HSCT produces donor-derived enzyme that does cross the BBB.
Australian Context
Specialist Centres:
- Sydney Children's Hospital Network - main paediatric MPS centre NSW
- Royal Children's Hospital Melbourne - Victorian MPS centre
- Queensland Children's Hospital - Queensland referrals
- Perth Children's Hospital - WA referrals
PBS-Funded ERT: Enzyme replacement therapy is PBS-funded for:
- MPS I: Laronidase (Aldurazyme) - Section 100 HSD
- MPS II: Idursulfase (Elaprase) - Section 100 HSD
- MPS IVA: Elosulfase alfa (Vimizim) - Section 100 HSD
- MPS VI: Galsulfase (Naglazyme) - Section 100 HSD
HSCT Services:
- Sydney Children's Hospital - main paediatric BMT centre
- Royal Children's Hospital Melbourne
- Access to international donor registries via ABMDR
Newborn Screening:
- MPS I included in some state newborn screening programs
- NSW, Victoria have implemented or trialing
- Enables early diagnosis and HSCT before cognitive decline
Support Organizations:
- MPS Society Australia - patient support and advocacy
- Australian Paediatric Orthopaedic Society - clinical guidelines
- ASGPM (Australasian Society for Genetic Medicine) - metabolic guidelines
Orthopaedic procedures including spinal fusion, carpal tunnel release, guided growth procedures, and corrective osteotomies are routinely performed at specialist paediatric centres with appropriate multidisciplinary support.
MPS Exam Quick Reference
High-Yield Exam Summary
MPS Types - Key Features
- •MPS I (Hurler) - most severe, cognitive decline, HSCT needed early
- •MPS II (Hunter) - X-linked, no corneal clouding, variable severity
- •MPS III (Sanfilippo) - severe CNS disease, minimal skeletal
- •MPS IV (Morquio) - NORMAL intelligence, WORST skeletal disease
- •MPS VI (Maroteaux-Lamy) - normal intelligence, cardiac valve disease
Dysostosis Multiplex (JARS PB)
- •J-shaped sella turcica
- •Anterior (inferior) vertebral beaking
- •Ribs - paddle or oar shaped
- •Short metacarpals with proximal pointing (bullet-shaped)
- •Pelvis - flared iliac wings, shallow acetabulum
- •Bones - widened diaphyses
Cervical Spine Assessment
- •ADI greater than 5mm = instability (child)
- •SAC less than 14mm = significant stenosis
- •Odontoid hypoplasia UNIVERSAL in MPS IV
- •Flexion-extension views in ALL MPS patients
- •MRI if ADI elevated or neurological symptoms
Surgical Priorities
- •Cervical fusion if ADI greater than 5mm or myelopathy
- •Genu valgum - guided growth in growing child
- •Carpal tunnel release - extended, open technique
- •Always assess cervical spine before ANY surgery
- •Specialist anaesthesia mandatory
Treatment Essentials
- •HSCT for MPS I before age 2 for cognitive benefit
- •ERT does NOT cross BBB or reverse skeletal disease
- •ERT available: MPS I, II, IVA, VI (PBS-funded)
- •Multidisciplinary care improves outcomes
- •Regular surveillance prevents complications
References
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Puckett Y, Mallorga-Hernández A, Montaño AM. Epidemiology of mucopolysaccharidoses (MPS) in United States: challenges and opportunities. Orphanet J Rare Dis. 2021;16(1):241.
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Lachman RS, et al. Mucopolysaccharidosis IVA (Morquio A Syndrome) and VI (Maroteaux-Lamy Syndrome): Under-recognized and Challenging to Diagnose. Insights Imaging. 2014;5(5):577-592.
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White KK, Harmatz P. Orthopedic management of mucopolysaccharide disease. J Pediatr Rehabil Med. 2010;3(1):47-56.
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Solanki GA, et al. Cervical cord compression in mucopolysaccharidosis VI (MPS VI): findings from the MPS VI Clinical Surveillance Program (CSP). Mol Genet Metab. 2016;118(4):310-318.
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Hendriksz CJ, et al. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J Inherit Metab Dis. 2014;37(6):979-990.
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Aldenhoven M, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015;125(13):2164-2172.
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White KK, et al. Analysis of a national MPS IVA registry: clinical characteristics, surgical interventions, and outcomes. J Bone Joint Surg Am. 2019;101(14):1256-1265.
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Harmatz P, et al. The Morquio A Clinical Assessment Program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab. 2013;109(1):54-61.