Also known as Sly syndrome, this is a rare problem with the metabolism that can affect several parts of the body. This condition is also a part of a group known as lysosomal storage disorders where the deficiency or improper functions of the lysosomal enzymes can result in the accumulation of complex carbohydrates in various tissues and organs of the body. The clinical presentation of this disorder varies among the affected individuals but all present short statures, skeletal abnormalities and a degree of intellectual disability. The estimated frequency of this condition is less than 1 in 250,000 births.
Causes
This disease develops as the result of a mutation in the gene identified as GUSB which produces the enzyme known as beta-glucuronidase that is necessary for the breakdown of sugar molecules called glycosaminoglycans (GAGs). The genetic mutation results in the reduced or the complete absence of the functional enzyme. The deficiency of this enzyme causes the accumulation of GAGs within cells, particularly inside the lysosomes. The accumulations of GAGS can cause an increase in the size of various tissues and organs. 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 severe form is characterized by the excess accumulation of fluid in the body before the birth which can result in stillborn or death shortly after the birth of the infant. The mild cases can develop symptoms in early childhood including short stature, large head (macrocephalic), spinal malformations such as mild curvature of the spine from side to side, coarse facial features and an abnormally large tongue. The cloudiness may develop in the corneas of the eyes between the ages of 7 months and 8 years. The multiple bone deformities include prominent breast bone, frequent hip dislocations, club foot, outward bowing of the ankles and ‘frozen’ joints called contractures. Additional symptoms can include enlarged liver and spleen, umbilical hernia, profound hearing loss, recurrent respiratory infections, heart problems and excessive hairiness. The affected people can also present developmental delays in speech and language.
Diagnosis
The diagnosis is based on the characteristic findings, evaluation of the family history and with various specialized tests. The prenatal diagnosis is possible with the amniocentesis that measures the activity of beta-glucoronidase. Alternatively, the urine analysis can show increased levels of mucopolysaccharides. The measurement of the beta-glucuronidase activity in the blood or the skin cells can also help diagnosis the condition. The molecular genetic testing can identify the genetic mutation responsible for the cause of this condition.
Treatment
There is no cure for this disease. The treatment is focused on providing supportive care and relief from the symptoms that are evident. Conditions such as bone deformities, cardiovascular abnormalities and hernias require surgical intervention. Genetic counseling may be beneficial for the affected individual and their family members.
References
https://rarediseases.org/rare-diseases/sly-syndrome/
http://mpssociety.org/mps/mps-vii/
https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-vii#inheritance
https://rarediseases.info.nih.gov/diseases/7096/mucopolysaccharidosis-type-vii
