Answers to questions families often have about caring for their child with mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder resulting from deficiency of the enzyme α-L-iduronidase. Lysosomes are the parts of cells that dispose of unwanted materials; if a deficiency exists, the unwanted products build up in the lysosomes, causing problems. Deficiency of this enzyme results in the accumulation of complex sugars known as glycosaminoglycans (GAGs). The resulting accumulation of GAGs in the lysosomes leads to progressive, multi-system organ damage. You may hear the terms Hurler, Hurler-Scheie, and Scheie syndromes to describe your child's condition. These terms are going out of use as symptoms often overlap between categories. The disease is best characterized as severe or attenuated MPS I.

There is a wide range of symptoms in children identified with MPS I, ranging from mild to severe manifestations. Some of the manifestations observed in affected individuals include:

• hernias, inguinal and umbilical
• facial features that become coarse over time
• frequent upper airway infections with ear infections
• hepatosplenomegaly
• corneal clouding
• cardiac involvement, valve disease
• progressive skeletal dysplasia (dysostosis multiplex)
• growth delay
• profound neurological involvement (in the severe form only)
• macrocephaly

The diagnosis of MPS I is established by:

• Confirming deficiency of α-L-iduronidase in peripheral blood leukocytes or cultured fibroblasts.
• Molecular genetic testing for mutations in IDUA, the gene that encodes α-L-iduronidase, can be used for confirmatory diagnostic testing.

For untreated children with MPS I (the severe form), prognosis is poor, with death in late childhood. Treatment is often successful in extending the life expectancy, although it may introduce its own complications. Children with attenuated MPS I often have normal or near normal life expectancy but need to be monitored closely and treated for any complications that may arise.

MPS I is an autosomal recessive condition. Parents of children with MPS I are obligate carriers of the condition—they both carry a gene for MPS I. The parents of a child with MPS I have a 25% chance of having another child with MPS I with each subsequent pregnancy.

Children with MPS I are treated by hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT), or a combination of both. Other experimental surgeries are also being investigated. Children with attenuated forms are managed more conservatively but require stringent clinical management particularly related to their cardiac and skeletal manifestations.

Having a child with this condition will significantly affect the life of the family. Families are encouraged to join support groups that may be helpful in adjusting to life-changes that may occur as a result of this condition (see below).

Yes. If 1 child has the severe phenotype, then all other affected children will be severely affected. If 1 sibling has attenuated MPS I, then it would be expected that other siblings would also have attenuated MPS I.

While there is no treatment that is completely curative, the 2 available therapies, HSCT and ERT, can increase life expectancy, improve quality of life, and treat some of the symptoms associated with MPS I.

Individuals with the attenuated forms of MPS I do not appear to have problems with fertility, therefore, they should be able to have children. Women with MPS I should be followed closely by a maternal-fetal medicine specialist given the cardiac, respiratory, and musculoskeletal complications involved in the condition. Individuals with severe MPS I do not usually reach reproductive age if untreated.

No. Most individuals with MPS I, regardless of their clinical diagnosis of severe or attenuated MPS I, will have little to no enzyme activity when assayed, therefore it can not be used to predict phenotype.

Research opportunities can be found on the National MPS Society website. See National MPS Society. This site provides information about the disorder, research, support for families, fundraising, and efforts to increase public awareness about MPS and related disorders. Allows users to contact and communicate directly with other parents and individuals with MSP I. Clinical studies can also be found on ClinicalTrials.gov. Children and Adolescents with MPS I (ClinicalTrials.gov)