Mucopolysaccharidosis

Mucopolysaccharidosis

Mucopolysaccharidosis (MPS) is a group of disorders with deficiency of

some lysosomal enzymes normally responsible for the breakdown of

mucopolysaccharides results in an accumulation and deposition of undegraded

or partially degraded mucopolysaccharides in the lysosomes of many tissues.

These are part of the lysosome storage disease family which are a group of

disorders associated with malfunctioning of lysosomes.

The mucopolysaccharides accumulate in the bone marrow, joints, eyes, ears

and teeth, along with visceral structures like Liver, Spleen, Arteries and the

Respiratory System.

Signs and Symptoms

All the diseases in this family share similar characteristics but in varying

severity. These features are seen in changes in bone, skeletal structure,

connective tissues, and organs. Neurological complications may include

damage to neurons, pain, impaired motor function. This results

from compression of nerves or nerve roots in the spinal cord or in the

peripheral nervous system. Cognitive defects occur due to accumulation of

Heparan Sulfate in the CNS that leads to intellectual disabilities. Additional

findings are short stature, heart abnormalities, breathing irregularities,

liver and spleen enlargement (hepatosplenomegaly), and/or neurological

abnormalities.

In many cases of MPS, affected infants are observed to be normal after birth

but symptoms appear after the age of 1 or 2.

Subdivisions

1.A) MPS I - H/S (Hurler/Scheie syndrome)

B) MPS I - H (Hurler disease)

C) MPS I - S (Scheie disease)

2. MPS II-(Hunter syndrome)

3. MPS III A, B, C, and D (Sanfillipo syndrome)

4. MPS IV A and B (Morquio syndrome)

5. MPS VI (Maroteaux-Lamy syndrome)

6. MPS VII (Sly syndrome)

7. MPS IX (hyaluronidase deficiency/Natowicz syndrome)

	Mucopolysaccharidosis	Mucopolysaccharidosis	Enzyme Deficiency	Accumulated products
	Type	Names
MPS I	MPS I - H	Hurler disease	α-L-iduronidase	Heparan sulfate & Dermatan sulfate
	MPS I - H/S	Hurler/Scheie syndrome	α-L-iduronidase	Heparan sulfate & Dermatan sulfate
	MPS I - S	Scheie disease	α-L-iduronidase	Heparan sulfate & Dermatan sulfate
MPS II	MPS II	Hunter syndrome	Iduronate sulfatase	Heparan sulfate & Dermatan sulfate
MPS III	MPS III A	Sanfilippo Syndrome A	Heparan sulfamidase	Heparan sulfate
	MPS III B	Sanfilippo Syndrome B	N-acetylglucosaminidase	Heparan sulfate
	MPS III C	Sanfilippo Syndrome C	Heparan-α-glucosaminide N-acetyltransferase	Heparan sulfate
	MPS III D	Sanfilippo Syndrome D	N-acetylglucosamine 6-sulfatase	Heparan sulfate
MPS IV	MPS IV A	Morquio Syndrome A	Galactose-6-sulfate sulfatase	Keratan sulfate & Chondroitin 6-sulfate
	MPS IV B	Morquio Syndrome B	β-galactosidase	Keratan sulfate
MPS VI	MPS VI	Maroteaux-Lamy syndrome	N-acetylgalactosamine-4-sulfatase	Dermatan sulfate
MPS VII	MPS VII	Sly syndrome	β-glucuronidase	Heparan sulfate, Dermatan sulfate & Chondroitin 4,6-sulfate
MPS IX	MPS IX	Natowicz syndrome	Hyaluronidase	Hyaluronic acid

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MPS I

MPS I - S

Scheie disease

Enzyme Deficiency - α-L-iduronidase

Formerly: Mucopolysaccharidosis type V

Hurler Syndrome

It is the most severe form of mucopolysaccharidosis. It occurs due to the

deficiency of alpha-L-Iduronidase enzyme. The GAGs Dermatan Sulfate and

Heparan Sulfate accumulate in the body. Symptoms of the disorder first

appear at six months to two years of age. Affected infants experience

recurrent UTI  and upper respiratory tract infections, noisy breathing and

persistent nasal discharge along with developmental delays. Other symptoms

may include clouding of the cornea of the eye, an enlarged tongue, severe

deformity of the spine, and joint stiffness. Mental development begins to

regress at about the age of two.

Scheie Syndrome

This is a very mild form of mucopolysaccharidosis. It has the same enzyme

deficiency of alpha-L-iduronidase. Individuals with Scheie syndrome have

normal intelligence, height, and life expectancy. Symptoms include stiff joints,

carpal tunnel syndrome, aortic regurgitation and clouding of the cornea that

results in reduced visual acuity.

Hurler-Scheie Syndrome

It is an extremely rare disorder that refers to individuals who have a less severe

form of Hurler syndrome, but a more severe form than Scheie syndrome. It

involves the deficiency of the enzyme alpha-L-Iduronidase.

Hunter Syndrome

It is an X-linked trait that occurs due to deficiency of Iduronate sulfatase. The

symptoms include mental retardation, skeletal deformity, deafness and

hepatosplenomegaly.

Sanfilippo Syndrome

It has 4 subdivisions under it. The types along with enzyme defects are listed

under:

1. Sanfilippo Type A – Heparan-N-sulfatase

2. Sanfilippo Type B – alpha-N-acetylglucosaminidase

3. Sanfilippo Type C – alpha-glucosamine acetyltransferase

4. Sanfilippo Type D – N-acetylglucosamine-6-sulfatase.

All types of Sanfilippo syndrome are characterized by varying degrees of

intellectual disability, progressive loss of previously acquired skills and hearing

loss. The patients may also experience seizures, unsteady gait, and aggressive

behavior.

Morquio Syndrome

It exists in two forms (Morquio Type A and B) and occurs because of a

deficiency of the enzyme N-acetyl-galactosamine-6-sulfatase and beta-

galactosidase, respectively.

	Morquio Syndrome	Characteristic Accumulation
1	Morquio Syndrome - Type A	Keratan sulfate & Chondroitin sulfate.
2	Morquio Syndrome- Type B	Only Keratan sulfate

The symptoms are predominantly skeletal deformities and bone abnormalities.

Mild mental retardation may be present. Symptoms may include growth

retardation,  prominent lower face, short neck, knock knees or genu valgum, flat feet,

kyphoscoliosis, developmentAL abnormality of the epiphyses in long bones and

pectus carinatum.

Maroteaux-Lamy Syndrome

It occurs due to deficiency of N-acetylglucosamine-4-sulfatase.

Symptoms observed are coarse facial features, umbilical hernia, pectus

carinatum, joint contractures, corneal clouding and heptasplenomegaly.

Sly Syndrome

It occurs due to deficiency of the enzyme beta-glucuronidase. It results in

accumulation of dermatan sulfate, heparan sulfate and chondroitin sulfate.

Symptoms include Hernia, Hydrocephalus, corneal clouding, short stature,

coarse facial features and heart disease.

Natowicz Syndrome

This is an extremely rare disorder. This disorder is due to hyaluronidase enzyme deficiency.

Findings in affected case are nodular soft-tissue masses around joints, episodes of painful swelling of the masses and some bone erosion.

Treatment

Major treatment options for MPS I are :

• Hematopoietic stem cell transplant (HSCT)
• Enzyme replacement therapy (ERT)

Enzyme replacement therapy

• Aldurazyme - alpha-L-iduronidase - Type I MPS.
• Galsulfase - recombinant enzyme -MPS VI (Marateaux-Lamy syndrome).
• Elaprase - MPS type II (Hunter syndrome)
• Vestronidase alfa - recombinant human lysosomal beta glucuronidase - MPS VII (Sly syndrome)

	Enzyme replacement therapy
	Aldurazyme	Type I MPS	alpha-L-iduronidase
	Galsulfase	MPS VI - Marateaux-Lamy syndrome	Recombinant enzyme
	Elaprase	MPS type II - Hunter syndrome	idursulfase
	Vestronidase alfa	MPS VII - Sly syndrome	Recombinant human lysosomal beta glucuronidase

Surgical care for specific conditions

• Hydrocephalus – Ventriculoperitoneal shunting
• Corneal clouding – Corneal transplantation
• Cardiovascular disease – Valve replacement
• Obstructive airway disease – Tracheostomy
• Orthopedic conditions – Carpal tunnel release; soft-tissue procedures, corrective osteotomy for progressive valgus deformity at the knee; posterior spinal fusion

	Specific Conditions	Surgical Care
1	Hydrocephalus	Ventriculoperitoneal shunting
2	Corneal clouding	Corneal transplantation
3	Cardiovascular disease	Valve replacement
4	Obstructive airway disease	Tracheostomy
5	Carpal tunnel Syndrome	Carpal tunnel release
6	Progressive valgus deformity at the knee	Corrective osteotomy
7	Severe spinal deformity	Posterior spinal fusion

All of the following mucopolysaccharidoses are autosomal recessive disorders EXCEPT :

1. Sanfilippo Type B
2. Hunter syndrome
3. Scheie disease
4. Hurler disease

	ANSWER
	Hunter syndrome

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Most of mucopolysaccharidoses are autosomal recessive disorders EXCEPT Hunter syndrome which is

1. Autosomal recessive
2. Autosomal dominant
3. X-linked recessive
4. X-linked dominant

	ANSWER
	Most of mucopolysaccharidoses are autosomal recessive disorders EXCEPT Hunter syndrome which is
	X-linked recessive
	Only MPS in which mother alone passes along the defective gene to a son

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Maroteaux–Lamy syndrome is due to deficiency of which enzyme?

1. Hyaluronidase
2. β-glucuronidase
3. N-acetylgalactosamine-4-sulfatase
4. N-acetylglucosamine 6-sulfatase

	ANSWER
	Maroteaux–Lamy syndrome is due to deficiency of ENZYME :
	N-acetylgalactosamine-4-sulfatase

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“Pebbled skin” is a typical finding of which of the following disease?

1. Hurler Syndrome
2. Scheie Syndrome
3. Hunter syndrome
4. Morquio Syndrome

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	ANSWER
	Hunter syndrome
	Pebbly ivory skin lesions on the back, arms, and thighs

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Short stature is seen in all mucopolysaccharidoses EXCEPT -

1. Hurler disease
2. Hunter syndrome
3. Scheie disease
4. Morquio Syndrome

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	ANSWER
	Scheie disease
	Short stature is seen in all MPS conditions except MPS IS - Scheie disease

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Elaprase is used for traetment of -

1. Hurler disease
2. Hunter syndrome
3. Morquio Syndrome
4. Maroteaux-Lamy syndrome

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	ANSWER
	Hunter syndrome
	ELAPRASE (idursulfase) is used for treatment of medicine for patients with Hunter syndrome (Mucopolysaccharidosis II, MPSII). Approved by the FDA in 2006

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