eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Mucopolysaccharidosis Type VI
Updated: Dec 11, 2008
Introduction
Background
The mucopolysaccharidoses (MPSs) are a group of inherited disorders that result from the deficiency of 1 or more of the lysosomal enzymes required for glycosaminoglycan (GAG) catabolism. GAGs, which are a major constituent of connective tissues, are long-chain complex carbohydrates that are usually linked to proteins to form proteoglycans and include chondroitin 4-sulfate, chondroitin 6-sulfate, heparan sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. Because GAGs are primarily found in connective tissue, the sites of pathology primarily include the skeleton, heart valves, and other areas with connective tissue stroma.
The clinical features of the MPSs result from lysosomal accumulation of partially degraded or undegraded GAGs and typically include coarse facies, corneal clouding, organomegaly, joint stiffness, dysostosis multiplex, hernias, short stature, and, in some disorders, mental retardation. The specific enzymatic deficiency and the resultant pattern of GAG degradation products determine the phenotype of each disorder. In general, dermatan, keratan, and chondroitin sulfate degradation products are associated with visceral manifestations, whereas the accumulation of heparan sulfate degradation products may be associated with mental deficiency.
Mucopolysaccharidosis type VI (MPS VI), which is inherited as an autosomal recessive trait, results from the deficiency of N- acetylgalactosamine 4-sulfatase (arylsulfatase B) activity and the lysosomal accumulation of dermatan sulfate. MPS VI is characterized by somatic features but not by mental retardation.
Pathophysiology
MPS VI is characterized by progressive connective-tissue organ involvement that results from continuous storage of dermatan sulfate in the skeleton, heart valves, spleen, liver, lung, dura, and cornea. Pathological examination of affected tissues reveals the presence of engorged lysosomes. Patients appear healthy at birth and have accelerated growth in the first year, followed by deceleration and short stature later in childhood. The diagnosis is usually made in early childhood when organomegaly, corneal clouding, coarse features, enlarged tongue, frequent respiratory illness or otitis media, and joint stiffness are all apparent. Other complications include hearing loss, chronic respiratory tract infections, sleep apnea, pulmonary hypertension, hydrocephalus, rapid-onset blindness, and cardiac valve insufficiency or stenosis.
Frequency
United States
The MPSs are rare disorders, and data concerning incidence are not widely available.
International
Several reports provide estimates of MPS VI incidence outside the United States. An Australian survey reported an incidence rate of 1 per 248,000 births from 1980-1996.1 Reports from Germany, and northern Portugal noted birth incidences of 1 case per 432,610 births and 1 case per 238,095 births, respectively.2,3
Mortality/Morbidity
MPS VI is characterized by substantial morbidity because of progressive accumulation of GAGs.
- Although mental development is normal, physical and visual defects can adversely affect psychomotor development.
- Growth may be normal for the first few years of life but then stops, resulting in dwarfism.
- Most patients have corneal clouding, which can interfere with vision. Sudden vision loss can occur and is related to increased intracranial pressure or possible compression of the optic nerve.
- Restricted joint movement is a common feature, and patients develop claw-hand deformities due to contractures.
- Cardiac involvement includes aortic and mitral valve dysfunction.
- Skeletal changes are typified by dysostosis multiplex.
- Cervical cord compression due to bony abnormality, atlanto-axial instability, and thickening of the dura can lead to extremity pain, loss of motor function and sensation in extremities, or both.
- Patients may also have restrictive airway disease, obstructive airway disease, or both.
- Age at death varies, and mild forms of the disease have been described with prolonged survival.
Race
MPS VI is panethnic, although increased birth frequency has been reported in certain populations (Turkish population living in Germany).2
Sex
MPS VI is inherited as an autosomal recessive trait and appears equally in males and females.
Age
MPS VI is an inherited disorder that typically manifests in early childhood with retarded growth, hepatosplenomegaly, and coarse facial features.
Clinical
History
- Individuals with mucopolysaccharidosis type VI (MPS VI) usually have a period of normal growth and development but later present when frequent respiratory infections or otitis media, inguinal or umbilical hernias, hepatosplenomegaly, coarse facial features, joint or spine abnormalities, and corneal clouding become evident.
- Because MPS VI is a recessive disorder, no family history is usually present.
Physical
- Facial features include the following:
- Coarse facial features (Compare the facial features with those of other family members to best appreciate the coarsening.)
- Macrocephaly
- Enlarged tongue
- Prominent forehead
- Possible coarse texture of hair
- Hepatomegaly and splenomegaly are often present in patients with MPS VI.
- Umbilical and inguinal hernias are common.
- Growth may be normal for several years and may then stop, resulting in a final stature of 90-140 cm. A short trunk with lumbar lordosis is typically present.
- Corneal opacities can be detected with slitlamp examination.
- Restricted joint movement, including claw-hand deformities, appears in the first few years of life.
- Examination of the skin frequently reveals hirsutism.
Causes
MPS VI results from the deficiency of N- acetylgalactosamine 4-sulfatase (arylsulfatase B) and the lysosomal accumulation of dermatan sulfate.
More on Mucopolysaccharidosis Type VI |
 Overview: Mucopolysaccharidosis Type VI |
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| Treatment & Medication: Mucopolysaccharidosis Type VI |
| Follow-up: Mucopolysaccharidosis Type VI |
| References |
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References
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Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis. 2005;28(6):1011-7. [Medline].
Pinto R, Caseiro C, Lemos M, et al. Prevalence of lysosomal storage diseases in Portugal. Eur J Hum Genet. Feb 2004;12(2):87-92. [Medline].
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Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: The Metabolic and Molecular Bases of Inherited Disease. 1995:2465-94.
O'Brien JF, Cantz M, Spranger J. Maroteaux-Lamy disease (mucopolysaccharidosis VI), subtype A: deficiency of a N-acetylgalactosamine-4-sulfatase. Biochem Biophys Res Commun. Oct 8 1974;60(3):1170-7. [Medline].
Poorthuis BJ, Wevers RA, Kleijer WJ, et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet. Jul-Aug 1999;105(1-2):151-6. [Medline].
Swiedler SJ, Beck M, Bajbouj M. 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 A. Apr 15 2005;134(2):144-50. [Medline].
Further Reading
Keywords
Maroteaux-Lamy syndrome, mucopolysaccharidosis type VI, arylsulfatase B deficiency, polydystrophic dwarfism, type VI mucopolysaccharidosis, MPS, MPS VI, coarse facies, corneal clouding, organomegaly, joint stiffness, dysostosis multiplex, hernias, short stature, mental retardation, otitis media, hearing loss, chronic respiratory tract infections, sleep apnea, pulmonary hypertension, hydrocephalus, rapid-onset blindness, cardiac valve insufficiency, dwarfism, hepatosplenomegaly, macrocephaly, claw-hand deformities, hirsutism
