Disease Progression

MPS I is a progressive, debilitating, and often life-threatening disease. Over time, the enzyme deficiency and resulting accumulation of GAG (dermatan sulfate and heparan sulfate) in tissues and cells has progressively debilitating and often fatal effects, usually due to obstructive airway disease, respiratory infection, or cardiac complications. In the most severe cases of MPS I, death usually occurs by age 10 although some patients may have a normal life span.[1]

Clinical symptoms are heterogeneous and are progressively limiting in nature. A few examples of disease progression include:

  • Cardiovascular disease is common in patients with MPS I. Cardiomyopathy (weak heart muscle) and endocardial fibroelastosis (stiff heart) are conditions that can occur in young people with severe MPS I (Hurler syndrome). Coronary artery disease (caused by GAG storage in the heart blood vessels) is like that seen in older people and can lead to death. Mildly affected patients with the attenuated form of MPS I (Scheie syndrome) may develop problems with the aortic or mitral valves; they may have slowly progressive valvular heart disease for years without any clinical effects. People with attenuated disease who have moderate-to-severe symptoms (Hurler-Scheie syndrome) can also develop valve disease and may need mitral or aortic valve replacement in their teens and twenties.
  • Muscoskeletal manifestations occur early in life, by about six months of age. It is common to observe mild bone abnormalities (detected by radiological methods), particularly with hip abnormalities, ovoid vertebrae, and widening of the ribs. Other skeletal abnormalities include a poorly formed pelvis, a gibbus deformity of the back, and shortened phalanges.[1] Eventually, progressive skeletal dysplasia involving all bones is seen in all types of MPS I. Joint stiffness is common in all forms of MPS I and the maximum range of motion may become limited.[1]
  • Developmental delay is usually apparent in patients with severe MPS I by 12 to 24 months of age, with a maximum functional age of two to four years. This is followed by slowed development and progressive regression in developmental skills until death.[1] People with attenuated disease who have moderate-to-severe symptoms may have normal or near normal intelligence, while mildly affected patients with the attenuated form have normal intelligence.
  • Physical appearance of some infants with severe and moderate-to-severe symptoms of MPS I may appear normal at birth, but as early as three months of age, parents may notice changes in the child's facial features.[2] The characteristic facial features of these patients include short noses, flat faces, prominent foreheads, and large heads, which tend to be longer than normal from front to back (scaphocephalism).[3] The appearance of mildly affected individuals with attenuated MPS I is extremely variable. Adults are often stocky in build and their trunks are shorter than their limbs. The neck may be short and stiff, and facial appearance unremarkable.

References:

  1. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135. Accessed April 11, 2017.
  2. Cleary, M.A., and Wraith, J.E. (1995) The presenting features of mucopolysaccharidosis type 1H (Hurler syndrome) Acta Paediatr 84: 337.
  3. Scheie, H.G., Hambrick, G.W., and Barness, L.A. (1962) A newly recognized forme fruste of Hurler's disease (gargoylism). Am J Ophthal 53: 753.