mucopolysaccharidoses

definition

· group of lysosomal storage disorders

· due to errors of metabolism of mucopolysaccharides

Epidemiology

· rare

· autosomal recessive

pathology

· polysaccharide glycosaminoglycans form sidechains of proteoglycans

· heparin-, dermatin-, keratin- sulphate

· defunct GAGs degraded by lysosomal enzymes

· enzyme deficiencies lead to accumulation of partially degraded GAGs in cells

· in liver, spleen, bones and other tissues

· spill over into blood and urine

clinical features

· six clinical syndromes identified

· have common features

· progressive disorder

· dwarfism

· vertebral deformity

· coarse facies

· hepatosplenomegaly

· mental retardation

· x-rays show dysplasia affecting

· vertebral bodies

· epiphyses

· metaphyses

· superficial similarity to SE and SM dysplasia

radiology

· hypoplastic epiphyses and vertebral bodies

· poorly modelled metaphyses

· short wide metacarpals

· underdeveloped mandible

· spatulate ribs and clavicles

· flared iliac wings

· shallow acetabulae

investigations

· diagnosed by

· clinical impression

· urine studies

· confirmed by

· enzyme assay on cultured fibroblast studies

Hurler’s syndrome

· MPS type 1

· infants look normal at birth

· develop typical appearance by age 2

· undersized

· coarse facies

· protruding tongue

· other features

· kyphosis

· hepatosplenomegaly

· joint stiffness

· corneal opacities

· respiratory difficulty

· cardiac anomalies

· death in later childhood from cardiac or respiratory problems

Hunter’s syndrome

· MPS type II

· X-linked recessive

· similar but less severe clinical features to Hurler’s syndrome

San Fillipo

· type III

· autosomal recessive

Morquio’s syndrome

· MPS type IV

· progressive development of

· dwarfism

· kyphosis

· short neck

· protruberant sternum

· joint laxity

· genu valgum

· face unaffected

· intellect normal

· vertebral bodies are typical

· platyspondyly (ovoid and hypoplastic)

· anterior beaking

· odontoid hypoplasia common