Mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body due to the accumulation of sugar molecules called glycosaminoglycans.

Overview

MPS I is a lysosomal storage disorder. It was once divided into three syndromes—Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome—but is now categorized into severe and attenuated types based on the severity of symptoms.

Symptoms

Children with MPS I often appear healthy at birth, though some may have an umbilical or inguinal hernia. Symptoms typically include:

• Physical appearance: Macrocephaly (large head), coarse facial features, and a large tongue (macroglossia).
• Organ enlargement: Enlarged liver and spleen (hepatosplenomegaly).
• Respiratory: Narrowed airways, frequent upper respiratory infections, and sleep apnea.
• Vision and Hearing: Corneal clouding, hearing loss, and recurrent ear infections.
• Skeletal: Short stature, joint deformities (contractures), and dysostosis multiplex (multiple skeletal abnormalities seen on x-ray).
• Neurological/Nerve: Carpal tunnel syndrome and narrowing of the spinal canal (spinal stenosis) in the neck.

Severe MPS I involves a decline in intellectual function and rapid disease progression, often leading to a shortened lifespan. Attenuated MPS I has milder features, and intellectual impairment may be absent.

Causes

Mutations in the IDUA gene cause MPS I. This gene provides instructions for producing the IDUA enzyme, which breaks down large sugar molecules called glycosaminoglycans (GAGs). A lack of this enzyme leads to the accumulation of GAGs within the lysosomes of cells, causing them to enlarge and disrupting normal cellular function.

Inheritance

This condition is inherited in an autosomal recessive pattern. Both copies of the gene in each cell must have mutations for the condition to occur. Parents of an affected individual each carry one copy of the mutated gene but typically do not show symptoms.