MucopolysaccharidesMedical GeneticsDr Derakhshandeh, PhD

Definition

A gel-like substance found in:

body cells mucous secretions synovial fluids

Mucopolysaccharidoses

Genetic disorders

Deficiency of enzymes necessary to breakdown mucopolysaccharides (MPS)

Excessive accumulation of mucopolysaccharides in body tissues

MucopolysaccharidosesResults:many serious physical disorders Various genetic deformities such as:skeletal deformities (especially of the face)mental retardationdecreased life expectancy

Examples

Hunter syndromeHurler syndromeScheie syndromeSanfilippo syndromeMorquio diseaseMaroteaux-Lamy syndrome

Hurler syndrome type I (Alpha-L-iduronate deficiency )

Hurler syndrome type I

Definition 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

Hurler syndrome (type I)

Hurler syndrome type I

Key Symptom ImagesMucopolysaccharidosis I (MPS I) Disease (Hurler, Hurler-Scheie, Scheie Syndromes)

Causes of the Hurler syndrome Inherited as an autosomal recessive traitMetabolic defect: inability The body's to make an enzyme: lysosomal alpha-L-iduronase

incidence & and risk factors Approximately 1 in 150,000 infants are affectedNewborn infants with this defect appear normal at birth By the end of the first year, signs of impending problems begin to develop

MPS (Type I)The children slowly developCoarse, thick, facial featuresProminent dark eyebrowsProgressive stiffness Mental retardation

Prevention Genetic counseling: important for parents with a family history of Hurler syndromePrenatal diagnosis:An amniocentesis in the amniotic fluid are then cultured and the a-L-iduronidase activity in the cells is determined.

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)

SymptomsUmbilical herniaDeafness Stiffness (in joints) Shortness of breath Abnormal bones of spine and claw hand

MPS: SignsHepatomegalySplenomegalyEnlarged tongue Retinal pigmentation Hip dislocationKyphosisHeart murmursHeart valve damage from thickening

Tests that may indicate the syndromeIncreased excretion of dermatan sulfate and heparan sulfate in the urine

Absence of lysosomal alpha-L-iduronidase (in cultured fibroblasts) Culture of cells from amniotic fluid obtained by amniocentesis for enzyme testing (prenatal testing)

Tests that may indicate the syndromeAbnormal histological staining of white blood cells called metachromasia X-ray of the skeleten X-ray of the spineX-ray of the chestECG

Hunter syndrome type II

(Sulpho-idoronide sulphatase deficiency )

Hunter syndrome type II

Hunter syndrome type II

Hunter syndrome type II (Sulpho-idoronide sulphatase deficiency )X-linkedCoarse, thick, facial featuresProgressive stiffness decreased mental development Hepatomegaly (liver enlargement) Splenomegaly (spleen enlargement) Abnormal bone x-rays

Sanfilippo syndrome type III

Sanfilippo syndrome type III

Sanfilippo syndrome type III

Sanfilippo syndrome type III

Definition

Sanfilippo syndrome is one of the hereditary mucopolysaccharide storage diseasesit 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 mucopolysaccharideThis substance is called heparan sulfate, and in Sanfilippo syndrome, large amounts of it are excreted in the urine

Alternative Names Mucopolysaccharidosis type IIIsubtypes A - B C - DType IIIA: heparan sulfate sulfatase deficiencyType IIIB: N-acety-glucos-aminidase-deficiencyType IIID: N-acetyl-glucos-amine-6-sulfate sulfatase deficiency

Sanfilippo syndrome Causes an autosomal recessive traitIt is possibly the most common of the mucopolysaccharide storage diseases It has a relatively late onset rather than during the first year of life

CausesCoarse, thick, facial featuresProminent dark eyebrowsProgressive stiffness gait disturbances speech disturbances decreased mental development that progresses to severe mental retardation

PreventionGenetic 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.

SymptomsFamily 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

Sanfilippo syndrome Signs and testsHepatomegaly (liver enlargement) Splenomegaly (spleen enlargement) Corneas clear Echocardiogram may show thickened heart Abnormal bone x-rays such as thickened skull and oval vertebrae

Sanfilippo syndrome Signs and testsSeizuresmental 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

Features and Characteristics children with Sanfilippo syndrome

Occasional enlarged head Coarse facial features

Coarse hair

Excessive hair growth

Joint stiffness

Sanfilippo syndromeSevere diarrhea or constipation Severe hearing loss Hyperactivity Aggressive and destructive behavior Poor attentionPhysical aggression Speech and language delay Sleep disturbance Severe intellectual impairment most often before 6 years of age Mild growth retardation Vision impairment

Morquio syndrome Type IV

Morquio syndrome Type IVSkeletal abnormality - hand

Skeletal abnormality: flattened vertebrae

Morquio syndrome Type IVsubtypes A & B

Type IVA: Galactose-6- sulfatase deficiency

Type IVB: b-Galactosidase deficiency

Features and Characteristics children with Morquio syndrome Joint stiffnessMild growth retardationStiff joints that may not extend fully Without mental retardation !Abnormal bone x-raysX-ray of the skeleten X-ray of the spineX-ray of the chest

PreventionGenetic 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.

Maroteaux-Lamy syndrome Type V

(N-Acetyl-galactose-amin-4-sulfatase (Arylsulfatase B)

Maroteaux-Lamy syndrome TypeV

Maroteaux-Lamy syndrome TypeV

Features and Characteristics Maroteaux-Lamy syndrome Coarse facial features

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.