MPS I Disease Spectrum

Historically, MPS I has been divided into three groups according to the type, severity, and progression of the symptoms.

Hurler Syndrome 

The historical term for the most severe version of the disease is "Hurler syndrome,” named after the doctor who first described this condition. The medical literature describes Hurler disease as a condition with very rapid disease progression, developmental delay, very severe physical problems, and early death.

Scheie Syndrome 

The historical term used for the attenuated version of the disease is “Scheie syndrome,” also named after the doctor who first described this condition. The medical literature describes Scheie disease as a condition with slower disease progression, no cognitive impairment, and a longer lifespan (into adulthood) compared to Hurler. It was originally considered to be a completely different disease from Hurler, and was even referred to as “MPS V” in the past.

Hurler-Scheie Syndrome

The historical term used to describe individuals who do not neatly fit into the Hurler or Scheie categories is "Hurler-Scheie syndrome.” The medical literature describes Hurler-Scheie disease as a condition with rapid disease progression, little or no developmental delay, and symptom severity and mortality in between what is associated with Hurler and Scheie.

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 ---

MPS I spectrum of disease

Our understanding of the molecular basis and the varied signs and symptoms of MPS I has evolved greatly over time. It is becoming increasingly clear that this disease is more complex and more varied than was previously assumed, and that this Hurler, Hurler-Scheie, Scheie classification system is an oversimplification that does not adequately reflect the tremendous variation in symptoms, presentation, and progression.

It is now perhaps more appropriate to view MPS I as a continuous spectrum of disease, with the most severely affected individuals (also known as Hurler) on one end of the spectrum and the less severely affected individuals (also known as Scheie) on the other end, with a whole range of different severities in between. Some physicians choose to use the term “attenuated” to refer to all individuals who are not at the most severe end of the spectrum.

It is difficult to predict how severe or mild the disease might be. Even with the same small amount of enzyme activity, and even within the same family, there can be variations in progression that cannot be explained by the enzyme level or mutation. Therefore, there is no perfectly reliable way to determine the exact course of disease for many individuals with MPS I. It is important to remember that whatever classification is given to you or your loved one’s condition, MPS I is a spectrum with a wide variety of symptoms and the disorder is extremely varied in its effects.

Although patients with MPS I will experience a progression of symptoms over time, they do not progress from one “type” of MPS I to another. For example, a patient with symptoms on the “Scheie” or “attenuated” end of the spectrum will not experience symptoms in the same time frame as those who are closer to the “Hurler” end.

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.