mucopolysaccharidoses mel biochem

Mucopolysaccharidoses

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Objective• To understand what is

mucopolysaccharidoses• T0 be able to list the features of

mucopolysaccharidoses• To know the types of

mucopolysaccharidoses and their causes with their diagnosis

Introduction •  GAG = long chains of sugar

carbohydrates in cells that help build bone ,cartilage, tendons , corneas, skin and connective tissue

• GAG is made up of chains amino sugar + uronic acid

• Deficiency of enzyme to breakdown GAG

• so excessive accumulation of GAG(glycosaminoglycan) in lysosomes of various tissues

• Will result in lysis of lysosome release of all hydrolytic enzyme tissue destruction

Mucopolysaccharidoses

• All are inborn errors of metabolism • All these diseases are inherited

(autosomal recessive traits) except Hunter’s disease (X-linked

• Clinically Progressive disorders

Groups of GAG:

• Hyaluronic acid • Chondroitin sulphate• Dermatan sulphate• Heparan sulphate • Keratan sulphate• Heparin

Features • Coarse facial features( flat nasal bridge,

thick lips, and enlarged mouth and tongue)• Thick skin• Corneal opacity• Mental retardation• Gargoyle appearance• Short stature• Claw like fingers

Diagnosis• Urine test• Enzyme assays• Prenatal diagnosis• Genetic counselling

Treatment• No cure • Medical care is given to improve

quality of life– Physiotherapy– exercise– changes in diet

Type 1( Hurler’s)• L- Iduronidase• Mental retardation+++• Skeletal deformity ++• Corneal opacity++• Dermatan Sulphate and Heparan

Sulphate in urine• 1:100,000

Type 2 ( Hunter’s)• Iduronate sulphatase• Mental retardation+• Skeletal deformity ++• No Corneal opacity• Deafness • Dermatan Sulphate and Heparan

Sulphate in urine• 1: 250,000

Type 3 ( Sanfilippo’s)• N – acetyl glucosaminidase and

heparan sulfatase• Mental retardation++• Skeletal deformity +• Corneal opacity+• Heparan Sulphate in urine• 3 types• 1:500,000

Type 4 ( Morquio’s)• Galactosamine sulfatase and b- D

galactosidase• Mental retardation+• Skeletal deformity +• Corneal opacity+• Epiphyseal dysplasia +• Keratan Sulphate and Chondroitin Sulphate in

urine• 2 types • 1 :75,000

Type 5 ( Scheie’s)• L- Iduronidase• No Mental retardation• Mild Skeletal changes• Corneal opacity++• Dermatan Sulphate in urine• 1: 100,000

Type 6 (Maroteaux- Lamy’s) • N- acetyl –b-D- Galactosamino-4-

Sulfatase• No Mental retardation• Skeletal deformity +++• Corneal opacity++• Dermatan Sulphate in urine• 1 :100,000

Type 7 ( Sly’s)• B- Gluronidase• Mental retardation+• Dermatan Sulphate and Heparan

Sulphate in urine• <1: 250,000

Conclusion • The accumulation of GAG and

defiency of enzyme can lead to severe clinical condition based on Their site of accumulationThe type of GAG that accumulate

• HHSMSMS

Reference • DM Vasudevan, Sreekumari S and

Kannan Vaidyanathan, Textbook of Biochemistry for Medical Students, 6th Edition.