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

Updated: Sep 28, 2018
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

The mucopolysaccharidoses (MPSs) are a family of metabolic disorders caused by deficiency of lysosomal enzymes needed to degrade glycosaminoglycans (GAGs), or mucopolysaccharides. [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 differ for the various disease types.

Mucopolysaccharidosis type I (MPS I) is the most common type of MPS. MPS I is heterogeneous, and symptom severity varies widely. Historically, the most-to-least severe subtypes of MPS I were as follows: Hurler syndrome (MPS IH, OMIM #607014), Hurler-Scheie syndrome (MPS I-HS, OMIM #607015), and Scheie syndrome (MPS IS, OMIM #6076016). Currently, since no biochemical differences between these subtypes have been identified and their clinical findings overlap, MPS I is now divided into two subtypes: severe MPS I and attenuated MPS I. Patients with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and a shorter lifespan.

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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. Alpha-L-iduronidase deficiency results in an inability of the lysosome to break down GAGs, namely dermatan sulfate (DS) and heparan sulfate (HS). This process is essential for normal growth and homeostasis of tissues. In this disease, GAGs progressively accumulate in the lysosomes, ultimately causing cell, tissue, and organ dysfunction by largely unknown pathophysiological mechanisms. Biochemically, alpha-L-iduronidase deficiency, as seen in patients with MPS I, causes an increase in the urinary excretion of dermatan sulfate (DS) and heparan sulfate (HS).

Hurler syndrome is caused by mutation in the gene (IDUA) that encodes alpha-L-iduronidase on chromosome 4. [15] Many different mutations have been found at this locus, including mutations that cause MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS I-HS (Hurler-Scheie syndrome), among others. MPS I and all subtypes are discussed in detail below.

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Epidemiology

Frequency

United States

The estimated incidence of severe mucopolysaccharidosis type I (MPS I) is about 1 in 100,000 newborns. Attenuated MPS I is less common and occurs in about 1 in 500,000 newborns.

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) encompasses a wide range. Death in early childhood can occur in the more severe form and can range to an adulthood lifespan in the attenuated form.

Race

Mucopolysaccharidosis type I (MPS I) is inherited as autosomal recessive and equally affects both sexes.

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Prognosis

MPS I-HS and MPS IS are considered attenuated forms. Symptoms tend to develop later in life, starting in the teenaged years and into the early third decade of life. Symptoms are milder than those observed in MPS IH (Hurler syndrome).

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Patient Education

Genetic counseling should be provided to families to explain autosomal recessive inheritance. Organizations and support groups for patients and families affected by MPS disorders include the following:

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