A Progressive and Heterogeneous Disease

As the burden of excess GAG increases, the clinical disease associated with MPS VI worsens. Like all MPS disorders, MPS VI is a heterogeneous disease; the age of onset, organ systems affected, severity of disease, and the rate of disease progression vary widely. Patients with rapidly advancing disease may present with marked disease during the first few years of life. Due to genetic mutations that allow a small amount of enzyme activity, some affected individuals display more slowly advancing disease and are diagnosed later in life, sometimes during adolescence or even adulthood. Initial symptoms are often common pediatric complaints, such as recurrent otitis media, recurrent sinopulmonary infections, slow growth, and umbilical or inguinal hernia. In virtually all cases the end result is similar: MPS VI becomes severely debilitating over time, and is associated with a shortened life span.^1-3

The clinical manifestations seen in MPS VI are very similar to those seen in the more prevalent MPS I (also known as Hurler, Hurler-Scheie or Scheie syndrome), with one important exception. Cognitive development is not typically affected in MPS VI.¹

Spectrum of Disease Progression. These 4 affected adolescents, aged 9-12 years, illustrate the spectrum of disease severity in MPS VI and the potential subtlety or severity of MPS signs and symptoms. Early referral and diagnosis is urgent, since even patients with slowly advancing disease eventually experience severe disability and a shortened life span.5
Photos 2-4 courtesy of The National MPS Society, Inc.
MPS VI advances at different rates in different patients Rapidly advancing disease appears early in life with marked signs and symptoms   While slowly advancing disease may not present with signs and symptoms until adolescence or later in life   Variability in clinical presentation creates a diagnostic challenge MPS VI presents with a broad range of clinical symptoms Initial symptoms may be subtle, especially in patients with slowly advancing disease Initial symptoms are often common pediatric complaints, such as recurrent otitis media, recurrent sinopulmonary infections, slow growth, and umbilical or inguinal hernia

1. Miller G, Partridge A. Mucopolysaccharidosis type VI presenting in infancy with endocardial fibroelastosis and heart failure. Pediatr Cardiol. 1983;4:61-62.
2. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 3. 8th ed. New York, NY: McGraw- Hill; 2001:3421-3452.
3. Paterson DE, Harper G, Weston HJ, Mattingley J. Maroteaux-Lamy syndrome, mild form—MPS vi b. Br J Radiol. 1982;55:805-812.
4. Wilcox WR. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144(5 Suppl):S3-S14. Review.
5. Swiedler SJ, Beck M, Bajbouj M, et al. Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Am J Med Genet; 2005:134A:144-150