Large, MPS

Question 1

[Met/MPS]

Mucopolysaccharidoses with typical dysmorphic/coarse features? (3)

Answer 1

MPS 1H (Herler)
MPS 2 (Hunter)
MPS 6 (Maroteaus-Lamy)

Question 2

[Met/MPS]

Mucopolysaccharidoses 1 types and enzyme defect?

Answer 2

Severe or attenuated (Hurler or Scheie, previously)

a-L-iduronidase defect

Question 3

[Met/MPS]

Mucopolysaccharidoses 2 types and enzyme defect?

Answer 3

Hunter

Iduronate sulfatase defect

Question 4

[Met/MPS]

Mucopolysaccharidoses 3 name and types?

Answer 4

Sanfilippo

A SGSH Heparin N-sulfatase
B NAGLU a-N-acetylglucosaminidase
C HGSNAT Acetyl CoA: a-glycosaminide
D GNS N-acetylglucosamine-6-sulfatase

Question 5

[Met/MPS]

Mucopolysaccharidoses 4 types and enzyme defect?

Answer 5

Morquio IVA: Galactose 6-sulfatase
Morquio IVB: b-galactosidase

Question 6

[Met/MPS]

Mucopolysaccharidoses 6 types and enzyme defect?

Answer 6

Maroteaux-Lamy

N-acetylgalactosamine 4-sulfatase (ARSB, arylsulphatase B)

(FYI, ARSA, arylsulphatase A deficiency, causes metachromatic leukodystrophy)

Question 7

[Met/MPS]

Mucopolysaccharidoses 7 types name?

Answer 7

Sly

Question 8

[Met/MPS]

Mucopolysaccharidoses 9 types and enzyme defect?

Answer 8

Natowicz

Hyaluronidase

Question 9

[Met/MPS]

Clinical presentation of untreated severe MPS 1 (Hurler) by age? (4)

Answer 9

At birth: non-specific, umbilical or inguinal hernia, frequent URI
By 1 year: coarse facial features, Gibbus deformity, progressive skeletal dysplasia
By 3 year: intellectual disability, hearing loss, corneal clouding
Death by 10 years of life without treatment

Question 10

[Met/MPS]

Clinical presentation of untreated attenuated MPS 1 (Hurler)?
- Onset age
- 4 organ systems

Answer 10

Onset between 1-10 years
Hearing loss
Corneal clouding
Respiratory involvement
Cardiac valvular disease

Question 11

[Met/MPS]

Treatment options for MPS 1 (Hurler)? (2)

Answer 11

Hematopoietic stem cell transplantation with severe MPS 1
Enzyme replacement therapy with Aldurazyme

Question 12

[Met/MPS]

Less effected symptoms from hematopoietic stem cell transplantation in severe MPS 1? (3)

Answer 12

HSCT has lesser effects on
- the skeletal and joint manifestations
- corneal clouding
- cardiac involvement

Question 13

[Met/MPS]

Inheritance pattern of MPS 2 (Hunter)?

Answer 13

X-linked

Question 14

[Met/MPS]

Classification (recently considering) for MPS 2 (Hunter)?

Answer 14

Early progressive and slowly progressive
(Disease has a wide variety, and has a continuum)

Question 15

[Met/MPS]

Diagnostic biochemical test and genetic test for MPS 1 (Hurler)? (3)

Answer 15

Enzyme activity: the lysosomal enzyme α-L-iduronidase (IDUA)
Elevation of glycosaminoglycan (GAG): dermatan sulfate, heparan sulfate
Gene: IDUA

Question 16

[Met/MPS]

Clinical presentation of usually seen only in early progressive MPS 2 (Hunter) compared to slowly progressive? (3 organ systems)

Answer 16

CNS: progressive cognitive deterioration
Resp: frequent URI, progressive airway obstruction
Cardiac: valvular disease, cardiomyopathy

Question 17

[Met/MPS]

Common Clinical presentation of both early progressive and slowly progressive MPS 2 (Hunter)? (5)

Answer 17

Macrocephaly, hydrocephalus
Macroglossia
Conductive and sensorineural hearing loss
Hepatosplenomegaly
Dysostosis multiplex (deposition of lipid like substance in body tissues)
Carpal tunnel syndrome
(No corneal clouding in Hunter)

Question 18

[Met/MPS]

Diagnostic biochemical test and genetic test for MPS 2 (Hunter)? (3)

Answer 18

Iduronate 2-sulfatase (I2S) enzyme activity
Glycosaminoglycan (GAG): dermatan sulfate, heparan sulfate
Gene: IDS

Question 19

[Met/MPS]

Treatment options for MPS 2 (Hunter)? (2)

Answer 19

Enzyme replacement therapy with Elaprase
Hematopoietic stem cell transplantation, but no RCT done

Question 20

[Met/MPS]

What based for classification of MPS 3 (Sanfilippo)?

Answer 20

Based on enzyme defects

MPS IIIA: N-sulphoglucosamine sulphohydrolase (m/c)
MPS IIIB: Alpha-N-acetylglucosaminidase,
MPS IIIC: Heparan-alpha-glucosaminide N-acetyltransferase
MPS IIID: N-acetylglucosamine-6-sulfatase

Question 21

[Met/MPS]

Clinical presentation of MPS 3 (Sanfilippo)? (3 phases)

Answer 21

Phase 1—developmental delay with recurrent URIs, diarrhea
Phase 2—severe, challenging behavior presents with hyperactivity and aggression, Precocious puberty
Phase 3—further neurologic deterioration, Death occurs by the 20s.

Question 22

[Met/MPS]

Treatment of MPS 3 (Sanfilippo)?

Answer 22

Supportive care
(HSCT considered not effective, ERT is limited due to BBB, developing intrathecal)

Question 23

[Met/MPS]

Characteristic first manifestation and onset of age for MPS IVA (Morquio A)?

Answer 23

Kyphoscoliosis, genu valgum (knock-knee), and pectus carinatum
Severe form: 1 - 3 years old

Question 24

[Met/MPS]

Intelligence level of progressed MPS IVA (Morquio A)?

Answer 24

Normal intellectual abilities

Question 25

# [Met/MPS] Name of Bony deformity in MPS Which MPS is associated?

Answer 25

Dystostosis multiplex Seen in MPS 1 (Hurler), MPS 2 (Hunter), MPS 4 (Morquio), MPS 6 (Maroteaux-Lamy) Less seen in MPS 3 (Sanfilippo)

Question 26

# [Met/MPS] Treatment for mucopolysaccharidosis IVA (MPS IVA) (Morquio A)?

Answer 26

Enzyme replacement therapy (elosulfase alfa, (Vimizim))

Question 27

# [Met/MPS] Category of disease Mucopolysaccharidosis type IVB (MPS IVB) belongs to?

Answer 27

GLB1-related disorders (GM1 gangliosidosis and mucopolysaccharidosis type IVB)

Question 28

# [Met/MPS] Subtypes of GLB1-related disorders that has mucopolysaccharidosis type IVB (MPS IVB)? (2)

Answer 28

GM1 gangliosidosis: infantile, late-infantile/juvenile, chronic MPS IVB (Morquio B)

Question 29

# [Met/MPS] Two disease spectrum of GLB1-related disorders?

Answer 29

Beta-galactosidase (GLB1) deficiency 1. GM1 gangliosidosis: severe to intermediate with neurodegeneration 2. Morquio IVB: only skeletal manifestation

Question 30

# [Met/MPS] Distinction between GM1 gangliosidosis and MPS IVB (Morquio B) in GLB1-related disorders?

Answer 30

GM1 gangliosidosis: neuronal degeneration MPS IVB (Morquio B): skeletal dysplasia

Question 31

# [Met/MPS] Treatment for mucopolysaccharidosis type VI (Maroteaux Lamy Syndrome)?

Answer 31

Enzyme replacement therapy: Naglazyme

Question 32

# [Met/MPS] Clinical characteristics of mucopolysaccharidosis type VI (Maroteaux Lamy Syndrome)? (3)

Answer 32

Joint degeneration Cardiovascular disease Reduced pulmonary function (Usually normal intelligence, might have learning difficulties from hearing loss)

Question 33

# [Met/MPS] Dignosis? Skin ‘pebbling’ between scapulae With coarse facies, joint stiffness, and carpal tunnel syndrome

Answer 33

MPS 2 (Hunter)

Question 34

# [Met/MPS] Treatment options for MPS type 1, 2, 3, 4, 6 and 7?

Answer 34

No ERT for MPS 3 (Sanfilippo) HSCT for MPS 1 (Hurler) (maybe MPS 2, Hunter) MPS1 (Hurler): Aldurazyme MPS2 (Hunter): Elaprase MPS4A (Morquio A): Elosulfase alfa MPS6 (Maroteaux-Lamy): Naglazyme

Question 35

# [Met/LSD] Diseases that have Enzyme replacement therapy available in lysosomal storage disease? (4)

Answer 35

Gaucher Fabry Pompe Wolman (lysosomal acid lipase (LAL) deficiency)