Mucopolysaccharidoses

Introduction to Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders characterized by deficiencies in lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAGs), also known as mucopolysaccharides. These disorders are part of the larger family of lysosomal storage diseases.

Key points:

  • Inheritance: Autosomal recessive (except MPS II, which is X-linked recessive)
  • Incidence: Collectively, about 1 in 25,000 live births
  • Progressive nature: Symptoms worsen over time due to accumulation of GAGs
  • Multisystemic involvement: Affects various organ systems including skeletal, cardiac, respiratory, and nervous systems

Classification of Mucopolysaccharidoses

MPS disorders are classified into seven main types based on the specific enzyme deficiency:

MPS Type Eponym Enzyme Deficiency Main GAGs Accumulated
MPS I Hurler, Hurler-Scheie, Scheie syndrome α-L-iduronidase Dermatan sulfate, Heparan sulfate
MPS II Hunter syndrome Iduronate-2-sulfatase Dermatan sulfate, Heparan sulfate
MPS III Sanfilippo syndrome (A, B, C, D) Various enzymes in heparan sulfate degradation Heparan sulfate
MPS IV Morquio syndrome (A, B) Enzymes in keratan sulfate degradation Keratan sulfate
MPS VI Maroteaux-Lamy syndrome N-acetylgalactosamine 4-sulfatase Dermatan sulfate
MPS VII Sly syndrome β-glucuronidase Dermatan sulfate, Heparan sulfate, Chondroitin sulfate
MPS IX Natowicz syndrome Hyaluronidase Hyaluronan

Pathophysiology of Mucopolysaccharidoses

The pathophysiology of MPS disorders revolves around the accumulation of partially degraded GAGs within lysosomes due to specific enzyme deficiencies. This accumulation leads to cellular dysfunction and tissue damage through several mechanisms:

  1. Cellular dysfunction: Accumulation of GAGs in lysosomes leads to cellular enlargement and dysfunction, affecting various cell types including fibroblasts, chondrocytes, and neurons.
  2. Tissue damage: Progressive accumulation results in tissue damage and organ dysfunction.
  3. Inflammatory response: GAG accumulation triggers chronic inflammation, contributing to tissue damage.
  4. Oxidative stress: Increased oxidative stress is observed in MPS, further contributing to cellular damage.
  5. Impaired autophagy: Lysosomal dysfunction affects cellular autophagy processes, leading to accumulation of damaged cellular components.
  6. Secondary storage: Accumulation of other substances (e.g., GM2 and GM3 gangliosides) occurs as a secondary effect, particularly in neurological forms of MPS.

The specific pattern of GAG accumulation and resulting clinical features depend on the particular enzyme deficiency and the types of GAGs affected.

Clinical Manifestations of Mucopolysaccharidoses

MPS disorders present with a wide range of clinical manifestations, varying in severity and onset depending on the specific type. Common features include:

  • Facial dysmorphism: Coarse facial features, broad nose, thick lips, enlarged tongue
  • Skeletal abnormalities:
    • Dysostosis multiplex
    • Joint stiffness and contractures
    • Short stature
    • Spine deformities (kyphosis, scoliosis)
  • Neurological involvement:
    • Developmental delay and regression
    • Cognitive impairment (variable)
    • Behavioral problems
    • Hydrocephalus
    • Spinal cord compression
  • Cardiovascular manifestations:
    • Valve abnormalities (particularly mitral and aortic)
    • Cardiomyopathy
    • Coronary artery disease
  • Respiratory issues:
    • Recurrent respiratory infections
    • Obstructive and restrictive lung disease
    • Sleep apnea
  • Ophthalmological problems:
    • Corneal clouding
    • Retinopathy
    • Glaucoma
  • Hearing loss: Both conductive and sensorineural
  • Hepatosplenomegaly
  • Umbilical and inguinal hernias

The severity and combination of these manifestations vary among different MPS types and even within the same type, leading to a spectrum of clinical presentations.

Diagnosis of Mucopolysaccharidoses

Diagnosis of MPS disorders involves a combination of clinical assessment, biochemical tests, and genetic analysis:

  1. Clinical suspicion: Based on characteristic physical features, developmental patterns, and multisystem involvement
  2. Screening tests:
    • Urinary GAG analysis: Quantitative and qualitative assessment of excreted GAGs
    • Dried blood spot enzyme activity assays: Useful for newborn screening and initial testing
  3. Confirmatory tests:
    • Enzyme activity assays: Measurement of specific enzyme activity in leukocytes, fibroblasts, or plasma
    • Genetic testing: Identification of pathogenic variants in the relevant genes
  4. Additional investigations:
    • Imaging studies: X-rays for skeletal abnormalities, MRI for CNS involvement
    • Echocardiography: Assessment of cardiac involvement
    • Ophthalmological and audiological evaluations
    • Neuropsychological assessment

Early diagnosis is crucial for timely intervention and management. Newborn screening for some MPS types (e.g., MPS I) is being implemented in some regions.

Treatment of Mucopolysaccharidoses

Management of MPS disorders requires a multidisciplinary approach. Treatment options include:

  1. Enzyme Replacement Therapy (ERT):
    • Available for MPS I, II, IVA, VI, and VII
    • Involves regular intravenous infusions of recombinant enzymes
    • Improves some systemic manifestations but has limited CNS penetration
  2. Hematopoietic Stem Cell Transplantation (HSCT):
    • Primarily used in severe MPS I (Hurler syndrome)
    • Can improve cognitive outcomes if performed early
    • Carries significant risks and requires careful patient selection
  3. Supportive care:
    • Management of specific complications (e.g., cardiac, respiratory, neurological)
    • Physical and occupational therapy
    • Speech and language therapy
    • Nutritional support
  4. Surgical interventions:
    • Orthopedic surgeries for skeletal deformities
    • Neurosurgical procedures (e.g., for hydrocephalus, spinal cord compression)
    • ENT procedures (e.g., tonsillectomy, adenoidectomy for sleep apnea)
  5. Emerging therapies:
    • Intrathecal enzyme replacement therapy
    • Gene therapy approaches
    • Small molecule therapies (e.g., substrate reduction therapy)

Treatment plans should be individualized based on the specific MPS type, disease severity, and patient characteristics. Regular follow-up and monitoring are essential for optimal management.

Prognosis of Mucopolysaccharidoses

The prognosis for individuals with MPS disorders varies widely depending on the specific type, severity of the disease, and available treatments:

  • Severe forms (e.g., MPS I Hurler): Without treatment, life expectancy is typically limited to the first decade of life. Early HSCT can significantly improve outcomes, especially cognitive function.
  • Attenuated forms: Individuals with milder variants (e.g., MPS I Scheie, some MPS VI patients) may have normal or near-normal life expectancy with appropriate management.
  • ERT-treatable forms: Introduction of ERT has improved the prognosis for several MPS types, particularly in terms of systemic manifestations and quality of life.
  • CNS involvement: Prognosis is generally poorer in MPS types with significant CNS involvement (e.g., severe MPS II, MPS III) due to limited treatment options for neurological symptoms.

Factors influencing prognosis include:

  • Age at diagnosis and initiation of treatment
  • Severity of organ involvement
  • Access to specialized care and advanced treatments
  • Development of treatment-related complications

Ongoing research and development of new therapies hold promise for improving long-term outcomes for individuals with MPS disorders.

MPS I (Hurler, Hurler-Scheie, Scheie Syndrome)

Enzyme Deficiency: α-L-iduronidase

Accumulated GAGs: Dermatan sulfate, Heparan sulfate

Inheritance: Autosomal recessive

Subtypes:

  • Hurler syndrome (severe)
  • Hurler-Scheie syndrome (intermediate)
  • Scheie syndrome (attenuated)

Clinical Features:

  • Coarse facial features
  • Developmental delay and cognitive impairment (severe in Hurler)
  • Skeletal deformities (dysostosis multiplex)
  • Corneal clouding
  • Hepatosplenomegaly
  • Cardiac valve abnormalities
  • Hearing loss
  • Recurrent respiratory infections

Diagnosis:

  • Enzyme activity assay in leukocytes or fibroblasts
  • Genetic testing of IDUA gene
  • Urinary GAG analysis

Treatment:

  • Enzyme Replacement Therapy (ERT) with laronidase
  • Hematopoietic Stem Cell Transplantation (HSCT) for severe Hurler syndrome
  • Supportive care and management of complications

Prognosis:

Varies widely depending on severity and treatment. With early HSCT, some Hurler patients may have near-normal cognitive development. Attenuated forms have better prognosis with ERT.

MPS II (Hunter Syndrome)

Enzyme Deficiency: Iduronate-2-sulfatase

Accumulated GAGs: Dermatan sulfate, Heparan sulfate

Inheritance: X-linked recessive

Subtypes:

  • Severe (neuronopathic)
  • Attenuated (non-neuronopathic)

Clinical Features:

  • Coarse facial features
  • Progressive cognitive impairment (in severe form)
  • Skeletal deformities
  • Joint stiffness
  • Hearing loss
  • Cardiac valve disease
  • Respiratory problems
  • Hepatosplenomegaly

Diagnosis:

  • Enzyme activity assay in plasma, leukocytes, or fibroblasts
  • Genetic testing of IDS gene
  • Urinary GAG analysis

Treatment:

  • Enzyme Replacement Therapy (ERT) with idursulfase
  • Supportive care and management of complications
  • Investigational therapies for CNS involvement

Prognosis:

Variable depending on disease severity. Severe form typically leads to death in the second or third decade. Attenuated form may have normal lifespan with appropriate management.

MPS III (Sanfilippo Syndrome)

Enzyme Deficiencies:

  • Type A: Heparan N-sulfatase
  • Type B: α-N-acetylglucosaminidase
  • Type C: Acetyl-CoA:α-glucosaminide acetyltransferase
  • Type D: N-acetylglucosamine 6-sulfatase

Accumulated GAG: Heparan sulfate

Inheritance: Autosomal recessive

Clinical Features:

  • Progressive cognitive decline
  • Behavioral problems (hyperactivity, aggression)
  • Sleep disturbances
  • Seizures
  • Mild coarse facial features
  • Mild skeletal abnormalities
  • Hearing loss

Diagnosis:

  • Enzyme activity assays specific to each subtype
  • Genetic testing of SGSH, NAGLU, HGSNAT, or GNS genes
  • Urinary GAG analysis

Treatment:

  • Primarily supportive care
  • Management of behavioral issues and seizures
  • Investigational therapies (gene therapy, substrate reduction therapy)

Prognosis:

Generally poor due to progressive neurodegeneration. Most patients survive into late teens to early 20s, with some surviving into their 30s.

MPS IV (Morquio Syndrome)

Enzyme Deficiencies:

  • Type A: N-acetylgalactosamine-6-sulfate sulfatase
  • Type B: β-galactosidase

Accumulated GAG: Keratan sulfate, Chondroitin-6-sulfate

Inheritance: Autosomal recessive

Clinical Features:

  • Severe skeletal dysplasia
  • Short stature with disproportionate trunk
  • Joint hypermobility
  • Corneal clouding
  • Hearing loss
  • Dental abnormalities
  • Cardiac valve disease
  • Spinal cord compression

Diagnosis:

  • Enzyme activity assays in leukocytes or fibroblasts
  • Genetic testing of GALNS (Type A) or GLB1 (Type B) genes
  • Urinary GAG analysis

Treatment:

  • Enzyme Replacement Therapy (ERT) with elosulfase alfa for Type A
  • Orthopedic surgeries
  • Management of spinal cord compression
  • Supportive care

Prognosis:

Variable, with some individuals surviving into adulthood. Quality of life is significantly impacted by skeletal complications. ERT has shown improvements in endurance and respiratory function.

MPS VI (Maroteaux-Lamy Syndrome)

Enzyme Deficiency: N-acetylgalactosamine 4-sulfatase (Arylsulfatase B)

Accumulated GAG: Dermatan sulfate

Inheritance: Autosomal recessive

Clinical Features:

  • Coarse facial features
  • Short stature
  • Skeletal deformities
  • Joint stiffness
  • Corneal clouding
  • Hearing loss
  • Cardiac valve abnormalities
  • Respiratory problems
  • Normal intelligence

Diagnosis:

  • Enzyme activity assay in leukocytes or fibroblasts
  • Genetic testing of ARSB gene
  • Urinary GAG analysis

Treatment:

  • Enzyme Replacement Therapy (ERT) with galsulfase
  • Supportive care and management of complications
  • Orthopedic surgeries as needed

Prognosis:

Variable depending on disease severity. ERT has improved pulmonary function, endurance, and quality of life. Some individuals may survive into adulthood with appropriate management.

MPS VII (Sly Syndrome)

Enzyme Deficiency: β-glucuronidase

Accumulated GAGs: Dermatan sulfate, Heparan sulfate, Chondroitin sulfate

Inheritance: Autosomal recessive

Clinical Features:

  • Hydrops fetalis in severe cases
  • Coarse facial features
  • Skeletal deformities
  • Hepatosplenomegaly
  • Cognitive impairment (variable)
  • Hernias
  • Cardiac valve abnormalities
  • Corneal clouding

Diagnosis:

  • Enzyme activity assay in leukocytes, fibroblasts, or dried blood spots
  • Genetic testing of GUSB gene
  • Urinary GAG analysis

Treatment:

  • Enzyme Replacement Therapy (ERT) with vestronidase alfa
  • Supportive care and management of complications

Prognosis:

Highly variable, ranging from death in early infancy to survival into adulthood. ERT has shown improvements in some clinical aspects, but long-term data is limited due to the rarity of the condition.

MPS IX (Natowicz Syndrome)

Enzyme Deficiency: Hyaluronidase

Accumulated GAG: Hyaluronan

Inheritance: Autosomal recessive

Clinical Features:

  • Soft tissue masses
  • Periarticular masses
  • Short stature
  • Mild coarse facies
  • Frequent otitis media
  • Normal intelligence

Diagnosis:

  • Enzyme activity assay in fibroblasts
  • Genetic testing of HYAL1 gene
  • Histological examination of tissue masses

Treatment:

  • Primarily supportive care
  • Surgical removal of problematic soft tissue masses
  • Management of joint problems

Prognosis:

Generally better than other MPS types. Limited data due to extreme rarity of the condition. Normal life expectancy is possible with appropriate management.



MPS I (Hurler, Hurler-Scheie, Scheie Syndrome)
  1. What enzyme deficiency causes MPS I?
    Alpha-L-iduronidase
  2. Which glycosaminoglycans accumulate in MPS I?
    Dermatan sulfate and heparan sulfate
  3. What is the inheritance pattern of MPS I?
    Autosomal recessive
  4. Which gene is responsible for MPS I?
    IDUA gene
  5. What are the three subtypes of MPS I?
    Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome
  6. Which subtype of MPS I is the most severe?
    Hurler syndrome
  7. What is the typical age of onset for Hurler syndrome?
    Before 1 year of age
  8. What is a common facial feature in MPS I patients?
    Coarse facial features
  9. What cardiac complication is common in MPS I?
    Valve abnormalities
  10. What skeletal abnormality is often seen in MPS I patients?
    Dysostosis multiplex
  11. What neurological symptom is common in severe MPS I?
    Cognitive impairment
  12. What eye problem is frequently associated with MPS I?
    Corneal clouding
  13. What respiratory issue often affects MPS I patients?
    Obstructive sleep apnea
  14. Which diagnostic test is used to confirm MPS I?
    Enzyme activity assay for alpha-L-iduronidase
  15. What treatment option can potentially cure MPS I if done early?
    Hematopoietic stem cell transplantation (HSCT)
  16. What is the name of the enzyme replacement therapy used for MPS I?
    Laronidase (Aldurazyme)
  17. How is enzyme replacement therapy typically administered in MPS I?
    Intravenous infusion
  18. What is the life expectancy for untreated severe MPS I (Hurler syndrome)?
    Usually less than 10 years
  19. Which subtype of MPS I has the mildest symptoms?
    Scheie syndrome
  20. What joint problem is common in MPS I patients?
    Joint stiffness and contractures
  21. What hepatic manifestation is often seen in MPS I?
    Hepatomegaly (enlarged liver)
  22. What prenatal test can diagnose MPS I?
    Chorionic villus sampling or amniocentesis with enzyme activity assay
MPS II (Hunter Syndrome)
  1. What enzyme is deficient in MPS II?
    Iduronate-2-sulfatase
  2. What is the inheritance pattern of MPS II?
    X-linked recessive
  3. Which gender is primarily affected by MPS II?
    Males
  4. What gene mutation causes MPS II?
    IDS gene
  5. Which glycosaminoglycans accumulate in MPS II?
    Dermatan sulfate and heparan sulfate
  6. What are the two main forms of MPS II?
    Severe (early progressive) and attenuated (slow progressive)
  7. What is a characteristic facial feature of MPS II patients?
    Coarse facial features
  8. What cardiac complication is common in MPS II?
    Valvular heart disease
  9. What respiratory problem frequently affects MPS II patients?
    Airway obstruction and sleep apnea
  10. What skeletal abnormality is often seen in MPS II?
    Dysostosis multiplex
  11. What neurological symptom is common in severe MPS II?
    Progressive cognitive impairment
  12. What hearing problem is associated with MPS II?
    Hearing loss (both conductive and sensorineural)
  13. What gastrointestinal issue is common in MPS II patients?
    Hepatosplenomegaly (enlarged liver and spleen)
  14. What skin condition is characteristic of MPS II?
    Pebbly ivory-colored skin lesions (particularly on the upper back and sides)
  15. Which diagnostic test confirms MPS II?
    Iduronate-2-sulfatase enzyme activity assay
  16. What is the name of the enzyme replacement therapy used for MPS II?
    Idursulfase (Elaprase)
  17. How is enzyme replacement therapy typically administered in MPS II?
    Weekly intravenous infusions
  18. What is the average life expectancy for severe MPS II without treatment?
    10-20 years
  19. What joint problem is common in MPS II patients?
    Joint stiffness and contractures
  20. What eye problem may occur in MPS II patients?
    Retinal degeneration
  21. What is a potential complication of MPS II in the spinal cord?
    Cervical spinal cord compression
  22. What prenatal test can diagnose MPS II in male fetuses?
    Chorionic villus sampling or amniocentesis with enzyme activity assay
MPS III (Sanfilippo Syndrome)
  1. How many subtypes of MPS III exist?
    Four (A, B, C, and D)
  2. What is the primary organ system affected in MPS III?
    Central nervous system
  3. What is the inheritance pattern of all MPS III subtypes?
    Autosomal recessive
  4. Which enzyme is deficient in MPS III-A?
    Heparan N-sulfatase
  5. What enzyme is lacking in MPS III-B?
    Alpha-N-acetylglucosaminidase
  6. Which enzyme is deficient in MPS III-C?
    Acetyl-CoA:alpha-glucosaminide acetyltransferase
  7. What enzyme is missing in MPS III-D?
    N-acetylglucosamine 6-sulfatase
  8. Which glycosaminoglycan accumulates in all subtypes of MPS III?
    Heparan sulfate
  9. What is the typical age of onset for MPS III symptoms?
    Between 2 and 6 years of age
  10. What behavioral change is often an early sign of MPS III?
    Hyperactivity and aggressive behavior
  11. What is the most common initial misdiagnosis for MPS III?
    Autism spectrum disorder
  12. What sleep disturbance is common in MPS III patients?
    Disrupted sleep-wake cycles
  13. What speech problem typically develops in MPS III patients?
    Progressive loss of speech
  14. What cognitive change occurs in MPS III patients over time?
    Progressive cognitive decline
  15. What physical feature is less pronounced in MPS III compared to other MPS types?
    Coarse facial features
  16. What diagnostic test is used to confirm MPS III?
    Enzyme activity assay specific to each subtype
  17. Is enzyme replacement therapy currently available for MPS III?
    No, it is still in clinical trials
  18. What is the average life expectancy for individuals with MPS III?
    Late teens to early 20s
  19. What late-stage neurological symptom is common in MPS III?
    Seizures
  20. Which subtype of MPS III is generally considered to have the most severe course?
    MPS III-A
  21. What skeletal abnormality is less prominent in MPS III compared to other MPS types?
    Dysostosis multiplex
  22. What is a potential treatment approach being researched for MPS III?
    Gene therapy
MPS IV (Morquio Syndrome)
  1. How many subtypes of MPS IV exist?
    Two (A and B)
  2. What enzyme is deficient in MPS IV-A?
    N-acetylgalactosamine-6-sulfate sulfatase
  3. Which enzyme is lacking in MPS IV-B?
    Beta-galactosidase
  4. What is the inheritance pattern of MPS IV?
    Autosomal recessive
  5. Which glycosaminoglycans accumulate in MPS IV-A?
    Keratan sulfate and chondroitin-6-sulfate
  6. What glycosaminoglycan accumulates in MPS IV-B?
    Keratan sulfate
  7. What is a distinctive physical feature of MPS IV patients?
    Short stature with disproportionately short trunk
  8. What skeletal abnormality is characteristic of MPS IV?
    Odontoid hypoplasia (underdevelopment of the odontoid process)
  9. What joint problem is common in MPS IV patients?
    Joint hypermobility
  10. What spinal deformity often develops in MPS IV patients?
    Kyphoscoliosis
  11. What cardiac issue is frequently seen in MPS IV?
    Valvular heart disease
  12. What respiratory problem is common in MPS IV patients?
    Restrictive lung disease
  13. What dental abnormality is often seen in MPS IV?
    Widely spaced teeth with thin enamel
  14. What eye problem is associated with MPS IV?
    Corneal clouding
  15. What hearing issue commonly affects MPS IV patients?
    Hearing loss (both conductive and sensorineural)
  16. Does MPS IV typically affect cognitive function?
    No, intelligence is usually normal
  17. What is a serious neurological complication in MPS IV due to cervical instability?
    Cervical spinal cord compression
  18. What diagnostic test confirms MPS IV?
    Enzyme activity assay specific to each subtype
  19. What is the name of the enzyme replacement therapy used for MPS IV-A?
    Elosulfase alfa (Vimizim)
  20. How is enzyme replacement therapy typically administered in MPS IV-A?
    Weekly intravenous infusions
  21. What is the average life expectancy for individuals with MPS IV?
    Variable, but many survive into adulthood
  22. What orthopedic intervention is often needed in MPS IV patients?
    Cervical spine fusion to prevent spinal cord compression
MPS VI (Maroteaux-Lamy Syndrome)
  1. What enzyme is deficient in MPS VI?
    N-acetylgalactosamine 4-sulfatase (Arylsulfatase B)
  2. Which glycosaminoglycans accumulate in MPS VI?
    Dermatan sulfate and chondroitin sulfate
  3. What is the inheritance pattern of MPS VI?
    Autosomal recessive
  4. Which gene mutation causes MPS VI?
    ARSB gene
  5. What are the two main forms of MPS VI based on severity?
    Rapidly progressing and slowly progressing
  6. What is a characteristic facial feature of MPS VI patients?
    Coarse facial features
  7. What skeletal abnormality is often seen in MPS VI?
    Dysostosis multiplex
  8. What cardiac complication is common in MPS VI?
    Valvular heart disease
  9. What respiratory problem frequently affects MPS VI patients?
    Obstructive and restrictive lung disease
  10. What eye problem is associated with MPS VI?
    Corneal clouding
  11. What hearing issue commonly affects MPS VI patients?
    Hearing loss (both conductive and sensorineural)
  12. What joint problem is common in MPS VI patients?
    Joint stiffness and contractures
  13. What hepatic manifestation is often seen in MPS VI?
    Hepatomegaly (enlarged liver)
  14. Does MPS VI typically affect cognitive function?
    No, intelligence is usually normal
  15. What spinal cord complication can occur in MPS VI patients?
    Cervical spinal cord compression
  16. Which diagnostic test confirms MPS VI?
    Arylsulfatase B enzyme activity assay
  17. What is the name of the enzyme replacement therapy used for MPS VI?
    Galsulfase (Naglazyme)
  18. How is enzyme replacement therapy typically administered in MPS VI?
    Weekly intravenous infusions
  19. What is the average life expectancy for individuals with rapidly progressing MPS VI without treatment?
    Usually into the late teenage years or early 20s
  20. What growth abnormality is common in MPS VI patients?
    Short stature
  21. What carpal tunnel-like syndrome is frequently observed in MPS VI patients?
    Trigger fingers or claw hand deformity
  22. What prenatal test can diagnose MPS VI?
    Chorionic villus sampling or amniocentesis with enzyme activity assay
MPS VII (Sly Syndrome)
  1. What enzyme is deficient in MPS VII?
    Beta-glucuronidase
  2. Which glycosaminoglycans accumulate in MPS VII?
    Dermatan sulfate, heparan sulfate, and chondroitin sulfate
  3. What is the inheritance pattern of MPS VII?
    Autosomal recessive
  4. Which gene mutation causes MPS VII?
    GUSB gene
  5. What is a common feature seen in newborns with severe MPS VII?
    Hydrops fetalis (abnormal accumulation of fluid in fetal tissues and cavities)
  6. What is the range of clinical severity in MPS VII?
    Highly variable, from severe neonatal-onset to milder adult-onset forms
  7. What skeletal abnormality is often seen in MPS VII?
    Dysostosis multiplex
  8. What cardiac complication is common in MPS VII?
    Valvular heart disease
  9. What respiratory problem frequently affects MPS VII patients?
    Recurrent respiratory infections and sleep apnea
  10. What hepatic manifestation is often seen in MPS VII?
    Hepatosplenomegaly (enlarged liver and spleen)
  11. What joint problem is common in MPS VII patients?
    Joint stiffness and contractures
  12. What neurological symptom may occur in severe cases of MPS VII?
    Cognitive impairment
  13. What eye problem is associated with MPS VII?
    Corneal clouding
  14. What hearing issue commonly affects MPS VII patients?
    Hearing loss (both conductive and sensorineural)
  15. Which diagnostic test confirms MPS VII?
    Beta-glucuronidase enzyme activity assay
  16. What is the name of the enzyme replacement therapy approved for MPS VII?
    Vestronidase alfa (Mepsevii)
  17. How is enzyme replacement therapy typically administered in MPS VII?
    Intravenous infusions every two weeks
  18. What is the life expectancy for individuals with MPS VII?
    Highly variable, depending on disease severity
  19. What growth abnormality is common in MPS VII patients?
    Short stature
  20. What is a potential complication of MPS VII in the spinal cord?
    Cervical spinal cord compression
  21. What prenatal test can diagnose MPS VII?
    Chorionic villus sampling or amniocentesis with enzyme activity assay
  22. What is a characteristic facial feature of MPS VII patients?
    Coarse facial features
MPS IX (Natowicz Syndrome)
  1. What enzyme is deficient in MPS IX?
    Hyaluronidase
  2. Which glycosaminoglycan accumulates in MPS IX?
    Hyaluronan (hyaluronic acid)
  3. What is the inheritance pattern of MPS IX?
    Autosomal recessive
  4. Which gene mutation causes MPS IX?
    HYAL1 gene
  5. How many cases of MPS IX have been reported in medical literature?
    Only a few cases have been reported
  6. What is a characteristic feature of MPS IX?
    Periarticular soft tissue masses
  7. What joint problem is common in MPS IX patients?
    Painful joint swelling and erosions
  8. Does MPS IX typically affect cognitive function?
    No, intelligence is usually normal
  9. What growth abnormality may be seen in MPS IX patients?
    Short stature
  10. What facial feature is often observed in MPS IX patients?
    Mild coarsening of facial features
  11. Are the severe systemic manifestations seen in other MPS types common in MPS IX?
    No, MPS IX generally has milder systemic involvement
  12. What diagnostic test confirms MPS IX?
    Hyaluronidase enzyme activity assay
  13. Is enzyme replacement therapy currently available for MPS IX?
    No, there is no specific enzyme replacement therapy available for MPS IX
  14. What is the primary treatment approach for MPS IX?
    Symptomatic and supportive care
  15. What imaging technique can be used to visualize the soft tissue masses in MPS IX?
    Magnetic Resonance Imaging (MRI)
  16. What is the life expectancy for individuals with MPS IX?
    Unknown due to the rarity of the condition, but likely near-normal
  17. Are cardiac complications common in MPS IX?
    No, cardiac involvement is not a prominent feature of MPS IX
  18. Are respiratory problems typically seen in MPS IX?
    No, respiratory issues are not commonly reported in MPS IX
  19. What skeletal abnormality is less prominent in MPS IX compared to other MPS types?
    Dysostosis multiplex is not a significant feature of MPS IX
  20. What is the typical age of onset for MPS IX symptoms?
    Childhood, but can vary
  21. What biochemical test can support the diagnosis of MPS IX?
    Elevated hyaluronan levels in serum and urine
  22. What is the primary clinical focus in managing MPS IX?
    Management of joint symptoms and mobility issues


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