Information for Primary Care Providers

MPS I is a progressive, multi-systemic disease and presenting features vary depending on disease severity. Early diagnosis is critical. 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.

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.

Abdominal hernia

In most individuals with MPS I, the abdomen bulges out due to their posture, weakness of the muscles, and the enlarged liver and spleen.[2] Frequently, part of the abdominal contents will push out behind a weak spot in the wall of the abdomen, forming a hernia. Mildly affected individuals with attenuated disease are less likely to have hernias.

Hernia Credit: Courtesy of Hodder/Arnold Publishers

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

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.

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

Abnormal gait

The feet of patients with severe forms of MPS I are broad and may be stiff with the toes curled under, rather like the hands. Many people with MPS I stand and walk with their knees and hips flexed. This, combined with a tight Achilles tendon, may cause them to walk on their toes. Some children with MPS I have knock-knees severe enough to require surgery.

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 joint contracture 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

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 severe 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.

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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.