Mucopolysaccharidosis type VI

Synonyms

7

Overview

Mucopolysaccharidosis type 6 (MPS 6), also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge and become inflamed or scarred. Skeletal abnormalities are also common in this condition. The rate at which symptoms worsen varies among affected individuals.

Symptoms

People with MPS VI generally do not display any features of the condition at birth. They often begin to show signs and symptoms of MPS VI during early childhood. Signs and symptoms may include:

  • Abnormality of the nasal alae 
  • Coarse facial features 
  • Limitation of joint mobility 
  • Mucopolysacchariduria
  • Opacification of the corneal stroma
  • Otitis media 
  • Sinusitis
  • Thick lower lip vermilion
  • Abnormality of the ribs
  • Genu valgum:
  • Hearing impairment
  • Hernia
  • Kyphosis
  • Short neck 
  • Splenomegaly
  • Abnormality of the heart valves 
  • Abnormality of the tongue
  • Cognitive impairment 
  • Visual impairment

Causes

MPS VI results from the deficiency of  N- acetylgalactosamine 4-sulfatase (arylsulfatase B) and the lysosomal accumulation of dermatan sulfate. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Mutations in the ARSB gene cause MPS VI. The ARSB gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the ARSB gene reduce or completely eliminate the function of arylsulfatase B. The lack of arylsulfatase B activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions such as MPS VI that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. The accumulation of GAGs within lysosomes increases the size of the cells, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the buildup of GAGs may also interfere with the functions of other proteins inside lysosomes, triggering inflammation and cell death.

Prevention

Counsel patients and their families about the autosomal recessive inheritance pattern of  MPS VI, the risk for occurrence in future pregnancies, and the availability of prenatal diagnosis.

Diagnosis

The diagnosis is usually made in early childhood when the symptoms appear. Ask your doctor for more information.

Prognosis

MPS VI is a progressive disorder with significant morbidity and early mortality. As with many genetic inborn errors of metabolism, considerable variation exists among individual patients. Therefore, the prognosis for a particular patient must be determined after consideration of the presentation and complications.

Treatment

Approved therapies:
N-acetylgalactosamine-4-sulfatase, recombinant human (Naglazyme) -  FDA-approved indication: For patients with mucopolysaccharidosis VI. Galsulfase has been shown to improve walking and stair-climbing capacity. 

Resources

Refer to research Publications.