Mucopolysaccharidosis type VI; Maroteaux-Lamy syndrome ..., (Mucopolysaccharidosis type VI, Maroteaux-Lamy syndrome) - Gen ARSB.
Mucopolysaccharidoses encompass a group of inherited metabolic diseases caused by the absence or malfunction of certain necessary for processing glycosaminoglycans, which help form bone, cartilage, tendons, corneas, skin and tissue conectivoor enzymes. The glycosaminoglycans (formerly called mucopolysaccharides) are also present in the fluid that lubricates joints. People with mucopolysaccharidosis not encode sufficient amounts of one of the 11 enzymes required to transform glycosaminoglycans protein and simpler molecules, or encode enzymes do not function properly. Over time, these glycosaminoglycans accumulate in cells, blood and connective tissues. This produces permanent and progressive cellular damage that affect the appearance and physical abilities, organs and body functions of the individual and, in most cases, mental development.
The type VI (MPS VI) mucopolysaccharidoses, also known as Maroteaux-Lamy syndrome, is a progressive disease which results in enlargement, swelling or scarring of many tissues and organs. Skeletal abnormalities are also common in this disease. The rate at which symptoms progress varies among affected individuals.
In general, individuals with MPS VI do not show any characteristic of the disease at birth and begin to show signs and symptoms throughout early childhood. The features of MPS VI include macrocephaly, hydrocephalus and macroglossia. Often these individuals also develop abnormalities of heart valves, hepatosplenomegaly and umbilical hernia or inguinal hernia. Furthermore, the airway can become narrow in some individuals, resulting in frequent respiratory infections and sleep apnea. Over time, the cornea becomes opaque, which can cause significant loss of vision. Other signs and symptoms may include recurrent ear infections and hearing loss. Unlike other types of mucopolysaccharidosis, type VI does not affect intelligence. Likewise, the disease causes various skeletal abnormalities which are most noticeable with age, including short stature, joint deformities that affect mobility, dysostosis multiplex, carpal tunnel syndrome and spinal stenosis in the neck that can compress and damage spinal cord.
The life expectancy of individuals with MPS VI depends on the severity of symptoms. If left untreated, can severely affected people survive only until the end of childhood or adolescence. Usually, people with milder forms of the disease live in adulthood, although their life expectancy can be reduced. Heart disease and obstruction of the airways are the main causes of death in people with MPS VI.
The type VI (MPS VI) mucopolysaccharidosis is due to mutations in the gene ARSB (arylsulfatase B), located on the long arm of chromosome 5 (5q14.1). This gene encodes an enzyme found in lysosomes called arylsulfatase B, involved in the breakdown of glycosaminoglycans (GAG). Specifically, arylsulfatase B eliminates two GAG called dermatan sulfate and chondroitin sulfate.
They have identified at least 146 mutations in the gene ARSB, corresponding to: missense mutations (111), and cutting mutations -splicing- connection (9), small deletions (17), small insertions (4), small indels 2 ) and larger deletions (3). Most of these mutations change nucleotides in the gene. All mutations reduce or eliminate the function of arylsulfatase B. Mutations that result in the complete absence of activity arylsulfatase B cause serious signs and symptoms. The lack of arylsulfatase B activity leads to the accumulation of GAGs within lysosomes. Due to the accumulation of molecules within lysosomes, this disease is considered an alteration of lysosomal storage. Accumulation of GAG increases the size of the cells, so many tissues and organs are enlarged. In addition, glycosaminoglycans are likely to interfere with the functions of other proteins inside lysosomes, causing inflammation and cell death.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with mucopolysaccharidosis type VI (MPS VI), by complete PCR amplification of the exons of the gene ARSB, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).