mucopolysaccharidosis type I

Intellectual disability

In the severe (Hurler) form, the buildup affects the brain, leading to developmental delay and intellectual disability. Attenuated forms can spare thinking and learning.

Global developmental delay

In the severe (Hurler) form, the brain is affected: development slows and then regresses, with loss of skills and thinking ability over time. The milder forms spare the intellect.

Hepatosplenomegaly

The liver and spleen enlarge (hepatosplenomegaly) as GAGs accumulate in them, often making the abdomen protrude.

Splenomegaly

The spleen also enlarges as storage material accumulates, often alongside an enlarged liver.

Short stature

Growth slows after infancy, so short stature is common in MPS I, especially in the more severe (Hurler) form.

Corneal opacity

Storage in the cornea makes it cloudy (corneal opacity), which can blur vision. It is one of the typical eye findings.

Opacification of the corneal stroma

Clouding of the cornea (the clear front of the eye) is characteristic of MPS I and can affect vision over time.

Hernia

Hernias (often at the navel or groin) are common in MPS I and may be an early sign that prompts diagnosis.

Flexion contracture

Joints become stiff and develop contractures (they cannot fully straighten), limiting movement of the hands, shoulders, hips, and other joints.

Diminished tissue alpha-L-iduronidase activity

The diagnosis rests on showing low activity of the alpha-L-iduronidase enzyme (in blood cells or a dried blood spot), confirmed by finding two faulty IDUA gene copies.

Hearing impairment

Hearing loss is common, from a mix of recurrent middle-ear disease and changes in the inner ear and hearing nerve pathway.

Hepatomegaly

Storage material builds up in the liver, so an enlarged liver (often together with an enlarged spleen) is a typical finding.

Macroglossia

An enlarged tongue (and thickened gums) can develop, which may affect feeding, speech, and the airway.

Coarse facial features

GAG buildup in the soft tissues of the face gradually produces a characteristic coarsening of the features, one of the more recognizable outward signs.

Dysostosis multiplex

A characteristic pattern of bone abnormalities called dysostosis multiplex develops, affecting the skull, spine, ribs, and long bones, and contributing to short stature and skeletal deformity.

Joint stiffness

Joints become stiff with limited movement, which can affect the hands, shoulders, and hips and reduce mobility.

Abnormal aortic valve morphology

Heart valves can thicken and work poorly in MPS I, so cardiac valve disease is part of the condition and needs monitoring.

Abnormal heart valve morphology

The heart valves thicken and can leak or narrow over time, so heart and valve function is monitored as part of routine care.

Mucopolysaccharidosis type 1

Diagnosed using: Alpha-L-iduronidase enzyme activity assay.

laronidase

Laronidase is enzyme replacement therapy: a manufactured copy of the missing alpha-L-iduronidase enzyme, given by weekly intravenous infusion. It helps the body's organs but does not cross into the brain well, so it has limited effect on the central-nervous-system disease of the severe form.

Used to help with: Mucopolysaccharidosis type 1.

hematopoietic stem cell transplantation

For severe (Hurler) disease, a hematopoietic stem cell transplant done early is the main disease-modifying treatment. The donor cells supply the missing enzyme and, unlike infused enzyme, can help protect the brain when the transplant is performed before significant damage occurs.

Used to help with: Mucopolysaccharidosis type 1.