Lysosomal Disorders - Mucopolysaccharidosis Type I

Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body.  MPS I is currently divided into the severe and attenuated types.

Children with MPS I often appear normal at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood.

Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).

People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections.

Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility.  Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord.

While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). In this form of the disorder, death typically occurs by age 10. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments.  Heart disease and airway obstruction are major causes of death in people with both types of MPS I.

Management of the multiple organ system involvement in MPS I requires a multi-specialty and multi-disciplinary approach, ideally guided by the Medical Home, that will be detailed below. Two relatively new treatment interventions are available to decrease the impact of the metabolic abnormalities patients with MPS I:

  • Successful hematopoietic stem cell transplantation (HSCT) increases survival, reduces facial coarseness and hepatosplenomegaly, improves hearing, and preserves normal heart function, however cardiac valvular disease, skeletal manifestations and corneal clouding may continue to progress. If HSCT is accomplished before evidence of significant developmental delay (usually under 2 years), the degree and rate of cognitive decline will likely be reduced.
  • Enzyme replacement therapy can significantly reduce liver size, increase height and weight, decrease joint restriction, lessen sleep apnea, and improve breathing in individuals with intermediate MPS I. The benefit of ERT in those with severe disease has not been assessed, however one patient with severe MPS, who had been treated for 3 years with ERT, continued to experience decline in respiratory status, musculoskeletal and spinal involvement, and developmental skills. [Thomas: 2006] Because the recombinant enzyme is not thought to cross the blood-brain barrier, the best option to reduce the risk of cognitive impairment remains early HSCT.
  • Combined ERT and HSCT is another option for individuals with severe MPS I. Providing ERT before and into the peri-HSCT period may improve the child's existing respiratory and cardiac manifestations to a certain extent which may reduce the risk of transplant-related complications. [Tolar: 2008]
  • Intrathecal ERT, injecting the enzyme into the spinal fluid, is a therapy currently under investigation for the treatment of cognitive decline in severe MPS I.

 

 

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