Severe and Attenuated MPS I Disease

MPS I is considered to be the prototypical lysosomal storage disorder with progressive multisystemic disease and presenting features that vary depending on the severity of the disease. The traditional clinical entities used to characterize the wide spectrum of clinical severity associated with MPS I diseases, from the most severe to less severe forms, are Hurler, Hurler-Scheie and Scheie syndromes. These do not adequately reflect the wide variation in clinical symptoms manifested by MPS I patients. There are several patients who do not fit precisely into any of these three clinical entities; moreover, the clinical phenotypes are not distinguishable biochemically by routine diagnostic procedures.

Because there is no clear delineation between the syndromes, patients are best described as having severe and attenuated forms of MPS I disease.[1] The greatest heterogeneity of symptoms is manifested by individuals exhibiting attenuated MPS I disease, which makes about 55% of all MPS I cases. Attenuated MPS I patients also make up a larger fraction of the prevalent population due to their increased longevity.

The table below lists the major clinical manifestations of the severe and attenuated forms of MPS I.

Severe and Attenuated MPS I Disease

Symptom Presentation Severe Patients Attenuated Patients
Stiffened Joints +++ ++
Skeletal Abnormalities +++ ++
Carpal Tunnel Syndrome +++ ++
Cardiac (Valvular) Disease +++ ++
Recurrent Ear, Nose, and Throat Infections +++ +
Obstructive Airway Disease/Sleep Apnea +++ +
Corneal Clouding +++ ++
Spinal Cord Compression +++ +
Hepatosplenomegaly/Splenomegaly +++ +
Inguinal or Umbilical Hernia +++ +
Hearing Loss +++ +
Cognitive Impairment +++ +
Growth Deficiencies +++ +
Coarse Facial Features +++ +
Communicating Hydrocephalus +++ ---
Abnormally Shaped Teeth +++ ---
 
Scale of Severity
Most Severe +++
Not Present ---

Did You Know?

MPS I is part of the mucopolysaccharidoses (MPS) family, a group of inherited diseases, each caused by accumulation of various glycosaminoglycans (GAGs) in the lysosomes. The exact GAGs that accumulate are different in each case. MPS diseases include seven sub-types and although each of the disorders can cause a variety of different symptoms, many of the diseases share similar symptoms, such as corneal clouding, short stature, and joint stiffness.

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. https://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62642135. Accessed February 2019.