Also known as Maroteaux-Lamy syndrome, this condition develops when an enzyme necessary for the breaking down of the sugar molecules is missing. As the result, the mucopolysaccharides can accumulate in various parts of the body causing progressive damage. As more cells become damaged, the symptoms can develop. The progression of the disease varies among the affected individuals with some only developing mild symptoms to others developing severe life-threatening complications. This rare genetic disease is estimated to affect around 1100 people globally.
Causes
This disease occurs as the result of a mutation in the gene identified as ARSB which produces an enzyme called arylsulfatase B that is necessary for the breaking down of sugar molecules known as glycosaminoglycans (GAGs). The genetic mutation results in the reduced or complete absence of this enzyme’s function. As a result, this can result in the accumulation of GAGs within cells particularly inside the lysosomes which are responsible for the digestion and recycling of different types of molecules. The accumulation of GAGs within the lysosomes can cause enlargement of various tissues and organs of the body. This condition is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell from the parents are defective.
Symptoms
The onset of symptoms and its progression varies greatly among the affected cases. Most of the patients do not present all the symptoms associated with this condition. The rapid progression of this disorder can occur before the age of three presenting walking problems by the age of 10, delayed or absent puberty and the risk of developing heart failure later in life. The slow progression of this disease becomes evident after five years of age presenting a decrease in their overall function and continuing to develop serious complications such as reduced pulmonary function, joint degeneration and cardiovascular disease. Although the intelligence remains unaffected, they may experience learning difficulties and short stature from growth restrictions. The skeletal abnormalities can include thickened short bones of the palm of the hands, abnormal ankle bones, severe malformation of the hip, thickened collarbones, a curvature of the spine and a prominent breastbone.
Diagnosis
The diagnosis is possible by identifying the features of this condition, the family history, a thorough clinical evaluation and a variety of specialized tests. The urine tests will be done to determine the levels of mucopolysaccharides and the high levels of dermatan sulfate can indicate this disorder. A blood sample and skin cells will be taken to assess the level of enzyme activity of arylsulfatase B which usually shows a deficiency or absent activity. Molecular genetic testing can confirm the diagnosis by identifying the mutation responsible for developing this condition.
Treatment
There is no cure for the disease. The treatment is usually focused on the symptoms that are evident in each case. The coordinated efforts of various specialists such as surgeons, pediatricians and orthopedists may be required to devise an effective treatment plan for the affected individual. The nagalazyme is an enzyme replacement therapy used in some cases that replace the missing or inactive enzyme with a recombinant version.
References
https://rarediseases.org/rare-diseases/maroteaux-lamy-syndrome/
http://mpssociety.org/mps/mps-vi/
http://www.naglazyme.com/about-mps-vi/
https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vi#inheritance
