Information for Rheumatologists

MPS I can affect many different organ systems and patients generally see several specialists before getting a diagnosis. Because joint involvement is typical in MPS I patients, referral to a rheumatologist is likely. Below are presenting symptoms observed by rheumatologists that may lead to clinical suspicion of MPS I and warrant more definitive testing.

Abnormal Growth

Growth in height is usually significantly less than normal but varies according to the severity of the disorder. Severely affected babies may be quite large at birth, and grow faster than average at first, but their growth usually slows down between 6 and 18 months of age and often stops altogether around 3 years of age.^[6]  The individual may not grow taller than 4 feet. In contrast, attenuated individuals usually grow to a relatively normal height, reaching 5 feet or more.

Children with neuronopathic MPS I generally have large heads, in part a consequence of the thickened calvaria that also produces a characteristic cranial appearance.^[6]  The head tends to be longer than normal from front to back (scaphocephaly) and the forehead is often particularly prominent, or prow-shaped, as a consequence of cranio-synostosis.

Bilateral Dyestesia

People with both severe and attenuated forms of MPS I sometimes experience pain and loss of feeling in their fingertips as a result of carpal tunnel syndrome (median nerve entrapment).^[1]  This syndrome is due to pressure on the median nerve as a result of thickened ligaments within the wrist; it may cause pain, and loss of feeling in the fingertips, but most patients lack these typical symptoms (pain, tingling, or numbness).^[3][4][5]  Because of the high incidence of the syndrome, routine electromyographic/nerve conduction velocity testing is typically recommended by the treating physician, even in the absence of patient complaints.^[5] 

Bilateral Dyestesia
Credit: Illustration courtesy of the National MPS Society

Claw Hands

The hands of MPS I patients are often short and broad with stubby fingers, and over time, the fingers stiffen and gradually become curved, due to limited joint movement. The tips of the fingers can become permanently bent over, giving rise to the characteristic claw hand deformity. 

Claw Hands
Credit: Courtesy of the National MPS Society

Hand/Wrist Pain

The hands of MPS I patients can be short and broad with stubby fingers. Over time, the fingers stiffen and gradually become curved, due to limited joint movement. The tips of the fingers can become permanently bent over, giving rise to the characteristic claw hand deformity. 

Some patients with MPS I may also have poor hand function, in part as a result of carpal tunnel syndrome (median nerve entrapment).^[1]  This syndrome is due to pressure on the median nerve as a result of thickened ligaments within the wrist; it may cause pain, and loss of feeling in the fingertips, but most patients lack these typical symptoms (pain, tingling, or numbness).^[3,4,5]  Because of the high incidence of the syndrome, routine electromyographic/nerve conduction velocity testing is typically recommended by the treating physician, even in the absence of patient complaints.^[5]  

Carpal Tunnel
Credit: Illustration courtesy of the National MPS Society

Hepatosplenomegaly

In severe patients and attenuated patients with moderate-to-severe symptoms, glycosaminoglycan (GAG) accumulation causes enlargement of both the liver and spleen (hepatosplenomegaly). The liver may also be enlarged in less severely affected individuals. The large liver does not usually cause liver problems, but it can interfere with eating and breathing.

Hepatosplenomegaly
Credit: Courtesy of J.E. Wraith

Hip Dysplasia

Hip dysplasia is found to some degree in nearly all children with severe MPS I and can also be found in children with attenuated MPS I. Most children with hip dysplasia eventually require corrective hip surgery. Surgery on the hips done more easily at a younger age, around 5-7, for the best results.^[7] 

Joint Pain

Joint stiffness is common in individuals with MPS I, and the maximum range of movement of all joints may become limited.^[2]  Later in the individual's life, joint stiffness may cause pain.

Joint Restriction

Joint manifestations are among the most significant disability and discomfort for patients with MPS I.^[2]  Almost all patients experience progressive arthropathy affecting all joints, and eventually leading to the loss of (or severe restriction of) range of motion.  This can be the first disease manifestation to be noticed in MPS I patients.

Joint Restriction
Credit: Courtesy of E. Kakkis, MD

Kyphoscoliosis

Thoracolumbar kyphosis (gibbus deformity) in the lower spine occurs in about 90% of children with severe MPS I. It develops from poor bone growth in the upper front part of the vertebrae, which results in a wedging of the vertebrae. Occasionally, children may suffer from both kyphosis and scoliosis, lateral curvature of the spine, making surgical intervention more likely and more complex.^[2] 

Gibbus Deformity
Credit:  Courtesy of E. Kakkis, MD

References

1. National MPS Society. Otitis Media: Ear Infections. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/  Accessed January 6, 2006.

2. Clarke, L.A. Clinical diagnosis of lysosomal storage diseases. In: Organelle Diseases: Clinical Features, Diagnosis, Pathogenesis and Management. Applegarth, D.A., Dimmick, J.E., and Hall, J.G. eds. London: Chapman and Hall Medical; 1997; 46.

3. Wraith, J.E., and Alani S.M. Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders. Arch Dis Child. 1990; 65:962-963.

4, Haddad, F.S., Jones, D.H., Vellodi, A., Kane, N., and Pitt, M.C. (1997) Carpal tunnel syndrome in the mucopolysaccharidoses and the mucolipidoses. J Bone Joint Surg Br. 1997; 79:578.

5. Van Heest, A.E., House J., Krivit, W., and Walker, K. Surgical treatment of carpal tunnel syndrome and trigger digits in children with mucopolysaccharide storage disorders. J Hand Surg Am. 1998; 23:239-241.

6. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, et al, editors. The Metabolic and Molecular Bases of Inherited Disease. Vol. III. 8th ed. New York: McGraw-Hill; 2001:3427-3452.

7. National MPS Society. Orthopedic disorders in children with MPS/ML: A Parent’s Guide. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/ Accessed January 6, 2006.

8. Myer, C.M.D. Airway obstruction in Hurler's syndrome - Radiographic features. Int J Pediatr Otorhinolaryngol. 1990;22:92-95.

9. Peters, M.E., Arya, S., Langer, L.O., Gilbert, E.F., Carlson, R., and Adkins, W. Narrow trachea in mucopolysaccharidoses. Pediatr Radiol. 1985; 15:226-227.

10. National MPS Society. Cardiac problems associated with the MPS Syndromes. Available at: http://www.mpssociety.org/content/4066/Fact_Sheets/  Accessed January 6, 2006.

11. Stone DL, Sidransky E. Hydrops fetalis: lysosomal storage disorders in extremis. Adv Pediatric. 1999;46:409-440.