Genetics of Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome)

Updated: Mar 20, 2017
  • Author: Paul R Harmatz, MD; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome and polydystrophic dwarfism, 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.

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. [1, 2] 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.

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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.

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Epidemiology

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. [3] Reports from Germany, and northern Portugal noted birth incidences of 1 case per 432,610 births and 1 case per 238,095 births, respectively. [4, 5] A survey of MPS VI in the Asia-Pacific region illustrates the paucity of information and the need for improved communication and sharing of information. [6] A study in Brazil produced evidence in favor of community-based screening. [7]

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). [4]

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, dysostosis multiplex, inguinal or umbilical hernias, recurrent respiratory illness, hepatosplenomegaly, and coarse facial features.

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