Information for Geneticists and Genetic Counselors
As an inherited genetic disorder, diagnosis of MPS I can help uncover presymptompatic symptoms and determine the risk of passing on the defective gene within families. Although the symptoms of MPS I overlap with those of other lysosomal storage disorders, the symptoms below may lead to clinical suspicion of MPS I disease.
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 FeaturesCredit: Courtesy of E. Kakkis, MD.
Patients with MPS I manifest a wide range of intellectual involvement. MPS I patients will suffer progressive and profound mental retardation, while patients on the attenuated end of the disease spectrum will exhibit little or no intellectual dysfunction. In severe patients historically known as Hurler patients, early development may be normal but developmental delay is usually suspected by 12 months. 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.
Hydrops fetalis, the excessive accumulation of serous fluid in the subcutaneous tissues and serous cavities of the fetus, is an extreme presentation of many of the lysosomal storage disorders. Symptoms during pregnancy include large amounts of amniotic fluid, thickened placenta, and ultrasound showing enlarged liver, spleen, or heart, and fluid buildup in the fetus' abdomen. After birth, symptoms may include pale coloring severe edema, especially in the baby's abdomen, enlarged liver and spleen, and respiratory distress. About half of babies with hydrops fetalis do not survive.
Children with severe MPS I generally have large heads, in part a consequence of the thickened calvaria that also produces a characteristic cranial appearance. 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.
National MPS Society. Available at: http://www.mpssociety.org.
Accessed March 15th, 2016.
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.
Wraith, J.E., and Alani S.M. Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders. Arch Dis Child. 1990; 65:962-963.
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.
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.
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.
- Myer, C.M.D. Airway obstruction in Hurler's syndrome - Radiographic features. Int J Pediatr Otorhinolaryngol. 1990;22:92-95.
- 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.
- Stone DL, Sidransky E. Hydrops fetalis: lysosomal storage disorders in extremis. Adv Pediatric. 1999;46:409-440.