IDS gene

Also known as: Hunter syndrome; Iduronate-2-Sulfatase deficiency; IDS deficiency; Sulfoiduronate sulfatase deficiency; SIDS deficiency – OMIM#309900

1. The Disease:

Mucopolysaccharidosis II (MPS II), or Hunter syndrome, is a lysosomal storage disease caused by deficiency or absence of the enzyme, iduronate-2-sulfatase, which is important in breaking down specific mucopolysaccharides, known as glycosaminoglycans (GAGs). MPS II is caused by mutations in the IDS gene and is inherited in an X-linked pattern. Males are primarily affected as they have a single X chromosome, and therefore, only one abnormal copy of the IDS gene is required to cause the disorder.

2. The Symptoms:

Infants are initially asymptomatic at birth and in the neonatal period. Symptoms typically become noticeable after 6 months of life. Lack of early signs or symptoms does not exclude the diagnosis.

  • The first symptoms include abdominal hernias, ear infections, persistent runny nose, and colds. As these symptoms are quite common among all infants, early diagnosis can be challenging.
  • Physical appearances include distinctive facial features (coarse feature, prominent forehead, broad nose and enlarged tongue), macrocephaly, short stature, thick and non-stretchy skin and an enlarged abdomen (due to hepatosplenomegaly). Frequent ear and upper respiratory infections may persist.
  • Additional features include enlargement of vocal cords causing a deep, hoarse voice, sleep apnea, hearing loss, contractures, seizures, developmental regression (loss of basic skills, functions, and intelligence), and severe intellectual disability.
  • MPS II is associated with a broad spectrum of clinical severity, and can be divided into two main forms: 1) severe, and 2) mild/attenuated. The age of onset and severity differ depending on the form. Signs of severe MPS II usually begin between ages two and four and progress more rapidly than in attenuated MPS II. Individuals with the attenuated form of MPS II usually do not develop signs until later in childhood, or even adolescence.

3. Actions to take in case of early diagnosis:

  • Early treatment is essential in preventing chronic symptoms.
  • Infants with a positive genetic test should have confirmatory MPS II testing through the measurement of I2S activity in dried blood spots or white blood cells.
  • As the clinical manifestations of Mucopolysaccharidosis type II are multisystemic, a multidisciplinary approach is required to proactively recognize and manage complications. Routine assessment of the various affected organs is necessary, and each specialist in the multidisciplinary team should oversee continuing evaluations once a clinical problem is identified.
  • For some infants with MPS II, detecting the condition early and beginning proper treatment may help prevent or delay some of the severe health outcomes associated with the condition.
  • As symptoms progress, surgeries (e.g.,shunting for hydrocephalus, tonsillectomy and adenoidectomy, positive pressure ventilation – CPAP or tracheostomy, carpal tunnel release, cardiac valve replacement, hip replacement) may be recommended to improve quality of life.
  • Enzyme replacement therapy (ERT) can be an effective treatment for symptoms of MPS II that do not involve the central nervous system.
  • It remains unclear if hematopoietic stem cell transplantation (HSCT) early in life significantly improves disease outcome.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information



  • Taylor M, Khan S, Stapleton M, et al. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol Blood Marrow Transplant. 2019;25(7). PMID: 3077251