Hurler syndrome, Hurler-Scheie Syndrome, and Scheie Syndrome (Mucopolysaccharidosis Type I)

Updated: Oct 12, 2014
  • Author: Maryam Banikazemi, MD; Chief Editor: Maria Descartes, MD  more...
  • Print
Overview

Background

Of the mucopolysaccharidoses (MPSs), mucopolysaccharidosis type I (MPS I) is by far the most common type. MPS I is heterogeneous, and the severity of symptoms widely varies. Historically, the range of most-to-least severe forms are as follows: Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome.

The MPSs are a family of metabolic disorders caused by the deficiency of lysosomal enzymes needed to degrade glycosaminoglycan (GAG). [1] GAG is an important constituent of the extracellular matrix, joint fluid, and connective tissue throughout the body. Progressive accumulation of GAG within the cells of various organs ultimately compromises their function. The major sites of disease differ depending on the specific enzyme deficiency; therefore, clinical presentation and approaches to therapy are different for the various disease types.

Next:

Pathophysiology

Mucopolysaccharidosis type I (MPS I) is a rare, inherited lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase. The disease is inherited in an autosomal recessive manner. The alpha-L-iduronidase deficiency results in an inability of the lysosome to break down GAG, namely dermatan sulfate (DS) and heparan sulfate (HS). This process is essential for normal growth and homeostasis of tissues. In this disease, GAG progressively accumulates in the lysosomes, ultimately causing cell, tissue, and organ dysfunction by largely unknown pathophysiological mechanisms. On a biochemical level, the alpha-L-iduronidase deficiency causes an increase in the urinary excretion of dermatan sulfate (DS) and heparan sulfate (HS) in patients with MPS I.

Hurler syndrome is caused by mutation in the gene (IDUA) that encodes alpha-L-iduronidase on chromosome 4.{R%ef15} Many different mutations have been found at this locus, including mutations that cause MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS IH/S (Hurler-Scheie syndrome), among others. MPS I and all subtypes are discussed in detail below.

Previous
Next:

Epidemiology

Frequency

United States

Precise figures for mucopolysaccharidosis type I (MPS I) incidence are lacking, but estimated incidence is approximately 1 case per 100,000 births.

International

The birth prevalence of mucopolysaccharidosis type I (MPS I) in England and Wales from 1981-2003 was 1.07 cases per 100,000 births. [2]

Mortality/Morbidity

Lifespan in mucopolysaccharidosis type I (MPS I) ranges from death in early childhood in the most severe form to adulthood in the least severe variant.

Race

Mucopolysaccharidosis type I (MPS I) is inherited in an autosomal recessive manner and affects both sexes.

Previous