HUNTER'S SYNDROME (X-LINKED RECESSIVE DISORDERS SERIES 3)

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Hunter syndrome is an X-linked recessive disorder in which your child’s body doesn’t properly digest certain sugar molecules like glycosaminoglycans. When these molecules build up in organs and tissues over time, they can cause damage that affects physical and mental development. Hunter syndrome is one of a group of diseases called mucopolysaccharidoses. Another name for Hunter syndrome is mucopolysaccharidosis type II or MPS II. It is a very rare disorder diagnosed in roughly 1 out of every 100,000 to 170,000 children.

SIGNS AND SYMPTOMS

The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth. The first symptoms may often include abdominal hernias, ear infections, runny noses, and colds. As the buildup of GAGs continues throughout the body's cells, signs of MPS II become more visible. The physical appearance of many children with the syndrome includes a distinctive coarseness in their facial features, including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. They may also have a large head and an enlarged abdomen. 

Hunter syndrome symptoms vary in severity and may include: stiff joints and thickening of facial features including nostrils and lips, delayed appearance of teeth or wide spaces between teeth, wide chest, and short neck, hearing loss that gets worse with time, delayed growth, especially starting around age 5, enlarged spleen and liver, and white growths on the skin.

CAUSES

A genetic mutation in the IDS gene causes Hunter syndrome. The IDS gene is responsible for regulating the production of an enzyme in your body called iduronate 2-sulfatase (I2S). The I2S enzyme breaks down complex sugar molecules called glycosaminoglycans (GAGs). (MPS II gets its name because GAGs were formerly called mucopolysaccharides.)MPS II is a type of lysosomal storage disorder, which is a condition that causes sugar molecules to accumulate inside lysosomes. These buildups can damage organs and tissues throughout the body.

DIAGNOSIS

The first laboratory screening test for an MPS disorder is a urine test for GAGs. Abnormal values indicate that an MPS disorder is likely. The urine test can occasionally be normal even if the child actually has an MPS disorder. A definitive diagnosis of MPS II is made by measuring I2S activity in serum, white blood cells, or fibroblasts from a skin biopsy. In some people with MPS II, analysis of the I2S gene can determine clinical severity. A urine test checks for unusually high levels of sugar molecules. Blood tests can show low or absent enzyme activity levels, which is also a sign of the disease. Genetic testing identifies mutations in the gene to confirm the diagnosis.

TREATMENT

Because of the wide variety of phenotypes, the treatment for this disorder is specifically determined for each patient. Until recently, no effective therapy for MPS II was available, so palliative care was used. Recent advances, though, have led to medications that can improve survival and well-being in people with MPS II.

1. Idursulfase, a purified form of the missing lysosomal enzyme, underwent a clinical trial in 2006 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.

2. Bone marrow transplantation and hematopoietic stem cell transplantation (HSCT) have been used as treatments in some studies. 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. 

3. In February 2019, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first "in-body" human gene editing therapy to permanently alter DNA – in a patient with MPS II. Clinical trials by Sangamo involving gene editing using zinc finger nuclease are ongoing as of February 2019.