This is an inherited disorder affecting the carbohydrate metabolism occurring mostly among the males. Also known as Hunter syndrome, it can present a wide range of symptoms based on its severity. This condition can affect several parts of the body with the severe form presenting decline in intellectual function with a rapid progression of the disease. The estimated life expectancy of the severe cases is around 10 to 20 years. The less severe case can live into adulthood without intellectual problems. This condition occurs in approximately 1 in 100,000 to 1 in 170,000 males.
Causes
This disease develops as the result of a mutation in the gene identified as IDS which produces the I2S enzyme that is necessary for the breakdown of sugar molecules known as glycosaminoglycans (GAGs). The genetic mutation results in the reduced or complete absence of the function of the I2S enzyme. The deficit of this enzyme causes the accumulation of GAGs within the cells particularly inside the lysosomes which are responsible for the digestion and recycling of different types of molecules. Lysosomal storage disorders are conditions that develop because of the accumulation of molecules inside the lysosomes. This accumulation can cause the increased size of several tissues and organs of the body. This disease is inherited in an X-linked recessive pattern meaning the defective gene is located on the X chromosome; one of the sex chromosome. As males only have a single X chromosome, one defective gene can cause this condition. Females have two X chromosomes; hence, both the copies of the gene must be defective to cause this disease. Hence, males are often more affected by this disorder than the females. One of the features of the X-linked inheritance is that the fathers cannot pass the X-linked traits to their male infants.
Symptoms
The symptoms include recurrent upper respiratory infections, hearing problems, liver and spleen enlargement, chronic runny nose, abdominal hernias, joint stiffness and growth failure. The coarse facial features can include thickening of the nostrils, lips and the tongue. A condition known as hydrocephalus can occur which is the accumulation of fluid in the cavities deep within the brain that is evident in most of the cases. Additional symptoms include a thick skin, hearing loss, nodular skin lesions, diarrhea and widely spaced teeth.
Diagnosis
The diagnosis is possible by detecting the reduced or absent enzyme activity responsible for developing this disorder. In the urine, the affected individuals present the accumulation of heparin and dermatan sulfates. The molecular genetic testing can also help confirm the diagnosis.
Treatment
There is no cure for this disease and the treatment is symptomatic and supportive. The enzyme replacement therapy has been approved as a treatment option for the affected individuals. A surgical intervention can help in the case of hernias and joint contractures. Other treatments can include the surgical removal of the tonsils and the adenoids, positive pressure ventilation to help keep the airway open for breathing issues and hearing devices for hearing loss. In the case of hydrocephalus, surgical implantation of a ventricular shunt may be necessary. Additional management interventions include physical and occupational therapy.
References
https://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-ii-2/
https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-ii#statistics
https://rarediseases.info.nih.gov/diseases/6675/mucopolysaccharidosis-type-ii
