Hunter syndrome

X linked recessive genetic condition

Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is a rare genetic disorder in which large sugar molecules called glycosaminoglycans (or GAGs or mucopolysaccharides) build up in body tissues. It is a form of lysosomal storage disease. Hunter syndrome is caused by a deficiency of the lysosomal enzyme iduronate 2 sulfatase (I2S). The lack of this enzyme causes heparan sulfate and dermatan sulfate to accumulate in all body tissues. Hunter syndrome is the only MPS syndrome to exhibit X linked recessive inheritance. By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers. and was subsequently approved by the United States Food and Drug Administration as an enzyme replacement treatment for MPS II. Idursulfase beta, another enzyme replacement treatment, was approved in Korea by the Ministry of Food and Drug Safety. Recent advances in enzyme replacement therapy (ERT) with idursulfase have been proven to improve many signs and symptoms of MPS II, especially if started early in the disease. After administration, it can be transported into cells to break down GAGs, but as the medication cannot cross the blood–brain barrier, it is not expected to lead to cognitive improvement in patients with severe central nervous system symptoms. Even with ERT, treatment of various organ problems from a wide variety of medical specialists is necessary. While transplantation has provided benefits for many organ systems, it has not been shown to improve the neurological symptoms of the disease. Although HSCT has shown promise in the treatment of other MPS disorders, its results have been unsatisfactory so far in the treatment of MPS II. ERT has been shown to lead to better outcomes in MPS II patients. Clinical trials by Sangamo involving gene editing using zinc finger nuclease are ongoing as of February 2019.

Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients have minimal neurologic involvement, they may survive into their 50s or beyond. A study in the United Kingdom indicated an incidence among males around one in 130,000 male live births.

The syndrome is named after physician Charles A. Hunter (1873–1955), who first described it in 1917.

Beginning in 2010, a phase I/II clinical trial evaluated intrathecal injections of a more concentrated dose of idursulfase than the intravenous formulation used in enzyme replacement therapy infusions, in hopes of preventing the cognitive decline associated with the severe form of the condition. Results were reported in October 2013. A phase II/III clinical trial began in 2014. In 2017, a 44 year old patient with MPS II was treated with gene therapy in an attempt to prevent further damage by the disease. This is the first case of gene editing being used in vivo in humans. The study was extended to six patients in 2018.

On 24 July 2004, Andrew Wragg, 38, of Worthing, West Sussex, England, suffocated his 10 year old son Jacob with a pillow, because of the boy's disabilities related to MPS II. A military security specialist, Wragg also claimed that he was under stress after returning from the Iraq War. He denied murdering Jacob, but pleaded guilty to manslaughter by reason of diminished capacity. Mrs Justice Anne Rafferty called the case "exceptional", gave Wragg a two year prison sentence for manslaughter, then suspended his sentence for two years. Rafferty said "nothing [was] to be gained" from sending Wragg to prison for the crime.