Hurler’s Syndrome

Hurler’s Syndrome is a disease caused by an enzyme deficiency

Pathophysiology

Type I mucopolysaccharidoses caused by a deficiency in alpha-1-iduronase

Signs and Symptoms

1) infants appear normal at birth with diagnosis usually made at 6-24 months 2) hepatosplenomegaly 3) corneal clouding 4) skeletal deformities 5) coarse facial features/prominent forehead 6) large tongue 7) stunted growth 8) joint stiffness 9) hearing loss 10) noisy breathing 11) copious nasal discharge 12) cardiovascular defects

Characteristic Test Findings

Radiographic – 1) large skull 2) thickened calvaria 3) shallow orbits 4) abnormal spacing of teeth 5) hypoplastic anterior vertebral bodies 6) enlarged diaphyses of long bones 7) short clavicles 8) oar-shaped ribs 9) short trapezoid-shaped phalanges Laboratory – 10) increased urinary excretion of GAGs

Associated Conditions

1) acute cardiomyopathy 2) communicating hydrocephalus 3) frequent upper respiratory tract infections 4) limited speech skills attained

Biochemistry

1) alpha-1-iduronase is an enzyme needed for degradation of GAGs 2) because of missing enzyme accumulation of dermatan and heparan sulfate occurs

Inheritance/Epidemiology

1) in untreated cases death by age 10 years owing to cardiovascular problems 2) autosomal recessive 3) gene for alpha-1-iduronase is on chromosome 4 (4p16.3)

Treatment

bone marrow transplantation before onset of disease progression

Tips for USMLE

1) term for the constellation of bony abnormalities is dyostosis multiplex 2) unfortunate descriptive term sometimes used is gargoylism 3) if question mentions an increased urinary excretion of GAGs, think Hurler’s (or one of the other mucopolysaccharidosis syndromes)