Deficiency in alpha-L-iduronidase results in abnormal lysososomal storage. There is an accumulation of mucopolysaccharides in various organs, causing organomegaly and eventual organ dysfunction. Severe reduction in the enzyme results in Hurler syndrome, while less severe deficiencies results in the Hurler-Scheie and Scheie syndromes.


Inheritance: autosomal recessive


Frequency: very rare (exact numbers uncertain due to incomplete ascertainment)


Clinical features of Hurler syndrome (MPS IH, severe deficiency):

(1) onset as a young child (1-3 years of age)

(2) developmental delay with mental retardation

(3) stunted growth

(4) enlargement of the tongue and coarse facial features

(5) hepatosplenomegaly

(6) recurrent upper respiratory tract (ear, nose) infections

(7) progressive facial and skeletal abnormalities (dysostosis multiplex)

(8) progressive corneal clouding and glaucoma

(9) cardiomyopathy

(10) severe diffuse coronary artery disease

(11) inguinal and umbilical hernias during infancy

(12) deafness

(13) compression of the cervical spinal cord and communicating hydrocephalus

(14) obstructive airway disease

(15) premature death before adolescence


Clinical features of Hurler-Scheie syndrome (MPS IH/S, intermediate deficiency):

(1) diagnosis is made in older childhood (3-8 years of age)

(2) less severe intellectual impairment, with many normal

(3) joint disorders (dysostosis multiplex with stiffness and deformity)

(4) aortic valve disease

(5) visual impairment due to corneal clouding, glaucoma and/or retinal degeneration

(6) obstructive airway disease

(7) deafness

(8) micrognathia common

(9) compression of the cervical spinal cord (pachymeningitis cervicalis)

(10) spondylolisthesis of the lower spine

(11) usually survive into adulthood


Clinical features of Scheie syndrome (MPS IS, mild deficiency):

(1) onset after age 5 with diagnosis between 10-20 years

(2) normal intellectual impairment

(3) joint stiffness, with deformities in hands and feet

(4) aortic valve disease

(5) visual impairment due to corneal clouding, glaucoma and/or retinal degeneration

(6) normal stature

(7) coarse facial features

(8) occasional obstructive airway disease

(9) occasional compression of the cervical spinal cord

(10) occasional spondylolithesis

(11) may have near normal lifespan


Biochemical features:

(1) excessive urinary dermatan and heparan sulfate excretion

(2) reduced to absent alpha-L-iduronidase activity

(3) accumulation of glycosaminoglycan in cultured fibroblasts


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