Hunter syndrome, also known as mucopolysaccharidosis II, belongs to the group of lysosomal metabolic disorders in which there is dysfunction in the breakdown of mucopolysaccharides (glycosaminoglycans) due to deficiency in an enzyme responsible for their breakdown. This leads to deposition of these glycosaminoglycans in various body tissues, which causes myriad of signs and symptoms in the disease.
Who Is At Risk For Hunter Syndrome?
Hunter syndrome is genetically inherited as an X linked recessive disorder. The genetic locus for Hunter syndrome is mapped to Xq28. The gene that is defective in this disorder is related to the enzyme iduronate sulfatase that helps in breaking down of glycosaminoglycans. So, any person who is defective in this enzyme is at risk for Hunter syndrome. (1)
The people who are the most at risk for Hunter syndrome are exclusively males and very rarely females owing to X linked recessive inheritance. This means that only females can transmit the disease to their offspring. Fathers can’t transmit the disease to their offspring being an X linked recessive inheritance disorder. A female will only be affected if both the mother and father are carriers of the defective chromosome, which is a very rare case as affected males do not usually reproduce; therefore, it is extremely rare for a female to be affected by it. Females might be affected if there is skewed X inactivation with the active X carrying mutation in allele of iduronate sulfatase enzyme. The severity in them depends on the type of mutation and the ratio of altered to non-altered X chromosome activity.
Individuals who are at a greater risk are those who have a positive family history of the genetic disease, as the siblings of the mother will be a carrier and the child who is affected, their male siblings will also have a greater chance of acquiring the defective gene.
People who are Jews and living in Israel are at a greater risk of the disease as this disease is more common among Jews of Israel and the estimated incidence is one case per 34,000 in Israel when compared to one case per 132,000 in United Kingdom.
Signs And Symptoms Of Hunter Syndrome
As the disease is a chronic disease, the signs and symptoms progressively worsen depending on the type of Hunter syndrome. Hunter syndrome is further divided into two types based on the severity and progression of the disease. Type A is a severe form and progresses rapidly with early onset of symptoms at around the age of 2-4 years. Type B is a milder form or attenuated form that progresses slowly with late onset of symptoms, which is about 4-6 years of age. In type B, neurological symptoms are not present and this is the differentiating factor between the two types.
Physical features include coarse facial features, large head, prominent forehead, flat nasal bridge, thick lips, large tongue, short stature, dysostosis complex (skeletal abnormality), hernias (umbilical or inguinal), hepatomegaly, splenomegaly, distension of abdomen, thick brows, coarse hair, excessive hair growth in the body, clawed fingers, pebbled skin, Mongolian spots, spacing between teeth, malformed teeth, enlarged gums, joint stiffness, abnormal gait, kyphosis, and carpal tunnel syndrome. Airway is also obstructed leading to recurrent upper respiratory tract infections, sore throat, adenoids, rhinorrhea, sinus infection, ear infection, cough, snoring, and sleep apnea.
Involvement of the heart causes valvular dysfunction, stenosis of cardiac arteries or aorta, cardiac enlargement, myocardial infarction and heart failure. When ears are involved it leads to progressive hearing loss (conductive, sensorineural or mixed). Involvement of the eye causes papilledema, vision loss (especially night time vision), retinal degeneration and glaucoma due to increased intracranial pressure.
Neurological symptoms include impaired or below normal intellect, delay in development, speech problems, communication problems, aggressiveness, behavioral problems, hyperactivity, cognitive deficiency, and attention deficit. Hydrocephalus causes increased pressure in the brain leading to headaches, seizures, and eye pain. Neurological complications can severely reduce quality of life.