Information for Pediatricians

MPS I is a progressive, multi-systemic disease and presenting features vary depending on disease severity. However, the earliest signs may be common in non-affected children and infants, which may complicate diagnosis. Still, the signs and symptoms below may lead to clinical suspicion of MPS I and warrant more definitive testing. Because the disease affects many organ systems, diagnosis may require collaboration with several specialists. Early diagnosis facilitates early disease management.

Coarse features

On the severe end of the disease spectrum, patients may have coarse facial features that develop slowly in the first year. By 2 years of age coarse features may be fairly obvious. This coarseness, which leads to the loss of fine detail in the infant’s facial features, is caused by storage of glycosaminoglycans (GAGs) in the orofacial region, as well as by underlying facial bone dysostosis. Thickened nostrils, lips, and ear lobules and enlargement of the tongue are all characteristics that become progressively more evident. Facial and body hypertrichosis is often seen by 24 months of age, at which time the facial and scalp hair may be coarse, straight and thatch-like.

The appearance of individuals with attenuated MPS I is extremely variable. They may have short stiff necks, broad mouths, square jaws and receding chins (micrognathia). Some with less severe MPS I can have almost normal appearance.

Coarse Features Credit: Courtesy of E. Kakkis, MD.

Developmental delay

Patients with MPS I manifest a wide range of intellectual involvement. MPS I patients will suffer progressive and profound cognitive impairment, while patients on the attenuated end of the disease spectrum will exhibit little or no intellectual dysfunction.[6] In severe patients historically known as Hurler patients, early development may be normal but developmental delay is usually suspected by 12 months.[6] Thereafter, there is usually progressive deterioration, and by 18 months, developmental delay is usually apparent. From this point on, patients generally do not progress in development but plateau for a number of years followed by a slow decline in intellectual capabilities.

Gibbus deformity

Gibbus deformity refers to a bump in the lower back due to an abnormal curvature of the spine. This forward bend, or thoracolumbar kyphosis, 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, making surgical intervention more likely and more complex. Gibbus deformity is usually observed within 10-14 months.

Gibbus Deformity Credit: Courtesy of E. Kakkis, MD

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

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

Macrocephaly

Children with severe MPS I generally have large heads, in part a consequence of the thickened calvaria that also produces a characteristic cranial appearance.[2] 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. Thickened nostrils, lips, and ear lobules and enlargement of the tongue are all characteristics that become progressively more evident.

Recurrent infections

In patients on the severe end of the disease spectrum, glycosaminoglycan (GAG) storage within the oro-pharynx with associated enlargement of the tongue, tonsils, and adenoids can lead to significant upper airway complications.[6] Lung volumes are often reduced because of the small thorax and hepatosplenomegaly limiting excursion of the diaphragm. Recurrent respiratory infections are common, and respiratory insufficiency is a major cause of mortality. Mildly affected patients with attenuated disease may not be affected by ear, nose, throat, and chest problems.

Otitis Media

What is otitis media? Otitis media (OM) is an infection or inflammation of the middle ear. This inflammation often begins when infections that cause sore throats, colds, or other respiratory or breathing problems spread to the middle ear. In MPS I, OM is caused, in part, by the buildup of glycosaminoglycans (GAGs) in the middle ear, nose, mouth, and throat.

Acute Otitis Media

Acute OM occurs when fluid is present in the middle ear, along with signs or symptoms of ear infection such as bulging eardrum often with pain, ear tugging, fever, irritability, decreased appetite, vomiting, and diarrhea. OM with effusion occurs when fluid is present without signs of infection. Although rare, complications can include tympanic membrane perforation, acute mastoiditis, cholesteatoma, meningitis, and epidural abscess.[1] Some degree of deafness is common for both severe and attenuated patients, and can be made worse by frequent ear infections. Mildly affected individuals with attenuated MPS I may be unaffected by ear, nose, throat, and chest problems.

Recurrent Otitis Media

Recurrent otitis media, infection of the middle ear, is one of the more stubborn problems for children with severe MPS I and to a lesser extent, individuals with attenuated MPS I who have moderate-to-severe symptoms.[1] Recurrent OM is caused, in part, by the buildup of GAGs in the middle ear, nose, mouth, and throat.

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References

  1. National MPS Society. Available at: http://www.mpssociety.org. Accessed April 11th, 2017.
  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: 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.
  7. Myer, C.M.D. Airway obstruction in Hurler's syndrome - Radiographic features. Int J Pediatr Otorhinolaryngol. 1990;22:92-95.
  8. 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.
  9. Stone DL, Sidransky E. Hydrops fetalis: lysosomal storage disorders in extremis. Adv Pediatric. 1999;46:409-440.