Rare Genetic Diseases: Mucopolysaccharidosis Type VI
Mucopolysaccharidosis type VI, also known as Maroteaux-Lamy syndrome, is a progressive condition that causes many tissues and organs to enlarge and become inflamed or scarred. The rate at which the symptoms worsen varies between the affected individuals.
Generally, the patients do not display any features of the condition until early childhood. The disorder affects 1 : 600,000 newborns. It is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
Characteristic symptoms of Mucopolysaccharidosis type VI include large head (macrocephaly), build up of fluid in the brain (hydrocephalus), as well as large tongue (macroglossia). Furthermore, affected individuals might develop heart valve abnormalities, enlarged liver and spleen (hepatosplenomegaly) and soft out-pouching around the belly button (umbilical hernia). Moreover, the clear covering of the eye (cornea) typically becomes cloudy, which can cause significant vision loss.
Mucopolysaccharidosis type VI is caused by the mutation on the ARSB gene. This gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). Mutations of the gene reduce or completely eliminate the function of arylsulfatase B.
The lack of the protein activity leads to the accumulation of GAGs within the cell, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules.
The accumulation of GAGs within lysosomes increases the size of the cells, which is why many tissues and organs are enlarged in this disorder. Furthermore, researchers believe that the build up of GAGs may also interfere with the functions of other proteins inside lysosomes, causing cell death.
The life expectancy depends on the severity of the symptoms. Without treatment, severely affected individuals may survive only until late childhood or adolescence. Heart disease and airway obstruction are primary causes of death.
