Hurler syndrome

Last reviewed 01/2018

Hurler syndrome is an autosomal recessive lysosomal storage disorder affecting mucopolysaccharide metabolism, the underlying defect being a deficiency of alpha-L-iduronidase. Hurler syndrome is also called gargoylism.

• mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that is caused by a deficiency in the lysosomal acid hydrolase, alpha-L-iduronidase
  • alpha-L-iduronidase cleaves iduronic acid residues from the nonreducing terminus of the long-chain polysaccharides derived from the proteoglycans, dermatan sulfate and heparan sulfate
  • alpha-L-iduronidase deficiency causes the blockage of further sequential degradation of these polysaccharides
    • causes lysosomal accumulation and urinary excretion of the partially degraded substrates
  • MPS I patients show a wide spectrum of clinical presentations ranging from the severe archetypical Hurler syndrome to an attenuated form called Scheie syndrome, where a few patients approach a near-normal clinical presentation
• patients with severe disease present with hydrocephalus, coarse facial features, corneal clouding, enlarged tongue, hepatosplenomegaly, hernia, cardiac disease, short stature, dysostosis multiplex, joint stiffness, clawed hands, fatigue and delay of mental development
  • in severe form of the disorder, the onset of the disease is rapid and progressive, with patients often suffering an early death before the teenage years
  • Scheie syndrome patients typically display variable clinical symptoms that can include coarse facial features, corneal clouding, cardiac valve disease, joint stiffness, clawed hands, malaise/fatigue and other somatic features
  • onset of these clinical symptoms is usually delayed compared to that in Hurler syndrome patients and the disease progression is less rapid
    • in some patients with an attenuated form of the disorder, intelligence can be normal, stature can be relatively normal and the patient can have a normal lifespan

Reference:

1. (1) E.F. Neufeld and J. Muenzer, The mucopolysaccharidoses. In: C.R. Scriver, A.L. Beaudet, W.S. Sly and D. Valle, Editors, The Metabolic Basis of Inherited Disease (7th ed.),, McGraw-Hill, New York (1995), pp. 2465-2494.