Transcript Mucopolysaccharides - Tehran University of Medical Sciences

Mucopolysaccharides
Dr Derakhshandeh, PhD
Medical Genetics
Definition
 A gel-like substance found in:
 body cells
 mucous secretions
 synovial fluids
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Mucopolysaccharidoses
Genetic disorders
Deficiency of enzymes necessary to
breakdown mucopolysaccharides (MPS)
Excessive accumulation of
mucopolysaccharides in body tissues
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Mucopolysaccharidoses
Results:
– many serious physical disorders
– Various genetic deformities such as:
skeletal deformities (especially of the
face)
mental retardation
decreased life expectancy
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Examples
Hunter syndrome
Hurler syndrome
Scheie syndrome
Sanfilippo syndrome
Morquio disease
Maroteaux-Lamy syndrome
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Hurler syndrome
type I
(Alpha-L-iduronate deficiency )
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Hurler syndrome
Definition
type I
An inherited disease (AR)
Storage of abnormal quantities
of this material
(mucopolysaccharide) in
different body tissues is
responsible for the symptoms
and appearance of the disease
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Hurler syndrome (type I)
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Hurler syndrome type I
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Mucopolysaccharidosis I (MPS I) Disease
(Hurler, Hurler-Scheie, Scheie Syndromes)
Key Symptom Images
Hernia
Corneal
clouding
Coarse
facial
features
Claw hand
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Causes of the Hurler
syndrome
Inherited as an autosomal recessive
trait
Metabolic defect: inability
– The body's to make an enzyme:
lysosomal alpha-L-iduronase
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incidence & and risk
factors
Approximately 1 in 150,000
infants are affected
Newborn infants with this
defect appear normal at birth
By the end of the first year,
signs of impending problems
begin to develop
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MPS (Type I)
The children slowly develop
Coarse, thick, facial features
Prominent dark eyebrows
Progressive stiffness
Mental retardation
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Prevention
Genetic counseling: important for
parents with a family history of
Hurler syndrome
Prenatal diagnosis:
An amniocentesis in the amniotic
fluid are then cultured and the
a-L-iduronidase activity in the
cells is determined.
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Symptoms
Short stature
Severe mental retardation
Thick, coarse facial features with low
nasal bridge
Full lips with a thick, large tongue
Increased body hair (hirsutism)
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Symptoms
Umbilical hernia
Deafness
Stiffness (in joints)
Shortness of breath
Abnormal bones of spine and claw
hand
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MPS: Signs
Hepatomegaly
Splenomegaly
Enlarged tongue
Retinal pigmentation
Hip dislocation
Kyphosis
Heart murmurs
Heart valve damage from thickening
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Tests that may indicate the
syndrome
Increased excretion of dermatan
sulfate and heparan sulfate in the
urine
Absence of lysosomal alpha-Liduronidase (in cultured fibroblasts)
Culture of cells from amniotic fluid
obtained by amniocentesis for
enzyme testing (prenatal testing)
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Tests that may indicate the
syndrome
Abnormal histological staining of
white blood cells called
metachromasia
X-ray of the skeleten
X-ray of the spine
X-ray of the chest
ECG
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Hunter syndrome type II
(Sulpho-idoronide sulphatase deficiency )
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Hunter syndrome type
II
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Hunter syndrome type II
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Hunter syndrome type II
(Sulpho-idoronide sulphatase deficiency )
X-linked
Coarse, thick, facial features
Progressive stiffness
decreased mental development
Hepatomegaly (liver enlargement)
Splenomegaly (spleen enlargement)
Abnormal bone x-rays
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Sanfilippo syndrome type III
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Sanfilippo syndrome type
III
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Sanfilippo syndrome type III
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Sanfilippo syndrome type III
Definition
Sanfilippo syndrome is one of the
hereditary mucopolysaccharide storage
diseases
it is characterized by the absence of one
of several enzymes
These enzymes help the body get rid of a
substance normally found outside of our
cells called a mucopolysaccharide
This substance is called heparan sulfate,
and in Sanfilippo syndrome, large amounts
of it are excreted in the urine
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Alternative Names
Mucopolysaccharidosis type III
subtypes A - B – C - D
Type IIIA: heparan sulfate
sulfatase deficiency
Type IIIB: Nacety-glucos-aminidasedeficiency
Type IIID: N-acetyl-glucosamine-6-sulfate sulfatase
deficiency
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Sanfilippo syndrome
Causes
an autosomal recessive trait
It is possibly the most common
of the mucopolysaccharide
storage diseases
It has a relatively late onset
rather than during the first
year of life
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Causes
Coarse, thick, facial features
Prominent dark eyebrows
Progressive stiffness
gait disturbances
speech disturbances
decreased mental development
that progresses to severe
mental retardation
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Prevention
Genetic counseling: important for
prospective parents with a family
history of Sanfilippo syndrome
Prenatal diagnosis:
An amniocentesis in the amniotic
fluid are then cultured and the
enzyme activity in the cells is
determined.
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Symptoms
Family history of Sanfilippo syndrome
May have normal growth during first few
years, but final height is below average
Delayed development followed by
deteriorating mental status
Deterioration of gait
Coarse facial features
Full lips
Heavy eyebrows that meet in the middle
of the face above the nose
Diarrhea
Stiff joints that may not extend fully
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Sanfilippo syndrome
Signs and tests
Hepatomegaly (liver enlargement)
Splenomegaly (spleen enlargement)
Corneas clear
Echocardiogram may show
thickened heart
Abnormal bone x-rays such as
thickened skull and oval vertebrae
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Sanfilippo syndrome
Signs and tests
Seizures
mental retardation
Activities of one of the enzymes may
be low in fibroblast skin cells
Urine may have increased heparan
sulfate
Abnormal pathological staining
character of white blood cells called
metachromasia
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Features and Characteristics
children with Sanfilippo syndrome
Occasional enlarged head
Coarse facial features
Coarse hair
Excessive hair growth
Joint stiffness
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Sanfilippo syndrome
Severe diarrhea or constipation
Severe hearing loss
Hyperactivity
Aggressive and destructive behavior
Poor attention
Physical aggression
Speech and language delay
Sleep disturbance
Severe intellectual impairment most often
before 6 years of age
Mild growth retardation
Vision impairment
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Morquio syndrome Type IV
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Morquio syndrome Type
IV
Skeletal abnormality - hand
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Skeletal abnormality: flattened
vertebrae
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Morquio syndrome Type IV
subtypes A & B
Type IVA: Galactose-6sulfatase deficiency
Type IVB: b-Galactosidase
deficiency
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Features and Characteristics
children with Morquio syndrome
Joint stiffness
Mild growth retardation
Stiff joints that may not extend
fully
Without mental retardation !
Abnormal bone x-rays
– X-ray of the skeleten
– X-ray of the spine
– X-ray of the chest
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Prevention
Genetic counseling: important for
prospective parents with a family
history of Morquio syndrome
Prenatal diagnosis:
An amniocentesis in the amniotic fluid
are then cultured and the enzyme
activity in the cells is determined.
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Maroteaux-Lamy syndrome
Type V
(N-Acetyl-galactose-amin-4sulfatase (Arylsulfatase B)
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Maroteaux-Lamy syndrome TypeV
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Maroteaux-Lamy syndrome TypeV
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Features and Characteristics
Maroteaux-Lamy syndrome
Coarse facial
features
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Treatment
At the present time, there is no cure for
MPS disorders.
Enzyme replacement therapy and gene
therapy are the two treatments that
researchers have been focusing on to
eventually cure MPS diseases.
There are a number of research
institutions around the world working on
finding a cure for the MPS diseases
including facilities in the United States,
Canada, England, and Australia.
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