Hurler syndrome (severe MPS I)

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease. Lysosomes are the parts of a cell that break down and recycle materials. In MPS I, they cannot break down long sugar chains called glycosaminoglycans, or GAGs, which slowly build up and damage organs.

MPS I ranges from severe to milder forms. Hurler syndrome is the severe form, and it is more common than the milder, or attenuated, forms. Attenuated MPS I starts later and progresses more slowly, and doctors weigh transplant differently for it.

Hurler syndrome is caused by changes in the IDUA gene, which carries the instructions for an enzyme called alpha-L-iduronidase. With little or no working enzyme, GAGs pile up inside cells throughout the body.

It is inherited in an autosomal recessive way. A child is affected when both copies of the gene carry a change, one from each parent, and parents are usually healthy carriers. Certain gene changes reliably point to the severe form, which can help doctors plan treatment early.

Babies usually look healthy at birth. Early signs can include hernias near the belly button or groin, frequent ear and nose-and-throat infections, and a curve in the spine. Facial features may become coarser over the first years.

Without treatment, development slows in early childhood and then children lose skills. The disease also affects the heart valves, the airway and breathing during sleep, hearing, the clear front of the eye (cornea), and bones and joints. Without treatment, children with severe MPS I may live only into late childhood.

In the United States, MPS I was added to the federal Recommended Uniform Screening Panel in February 2016. Many babies can now be found before symptoms. A low enzyme result on the newborn screen needs follow-up tests to confirm the diagnosis and to tell the severe form from milder ones.

Families often learn the diagnosis in a baby’s first year or two, then face many tests, weekly enzyme infusions and a transplant decision in a short time. Transplant brings chemotherapy, weeks in the hospital, infection precautions and months of close follow-up. It also carries serious risks, including graft failure, graft-versus-host disease and death. A 2011 European expert consensus reported that these risks had fallen considerably, helped by shared international guidelines.

After transplant, many children still need care for their bones and joints. Many also need ear, nose and throat care, speech therapy, and learning and family support. In an international study of 217 children with Hurler syndrome whose transplants took, most still had a considerable amount of ongoing disease, and the amount varied widely.

In that study, children who were younger at transplant and whose thinking skills were better preserved beforehand tended to have better learning later on. Needs change as children grow, so families benefit from a team that follows them over many years.

A transplant for Hurler syndrome uses blood-forming stem cells from another person. European transplant guidance for storage diseases ranks donors in this order: a matched family member who is not a carrier, then a matched unrelated donor, then a matched family member who is a carrier. Both parents are carriers, and half-matched (haploidentical) family transplants are rarely used for these diseases.

Donated umbilical cord blood is often preferred over bone marrow for storage diseases like Hurler syndrome. It can usually be ready soonest, and children who receive it tend to end up with a higher share of donor blood cells, though a cord blood graft may be rejected a little more often. Normal enzyme levels and fully donor-derived blood cells after transplant are linked with better long-term results.

Many children have no matched brother or sister who is free of the gene change. For them, unrelated adult volunteers and public cord blood donations are important donor options. Because the best window closes in early childhood, teams aim to keep the time between diagnosis and transplant short.