Mucopolysaccharidosis 2 presents with a progressive multisystem involvement due to glycosaminoglycan accumulation in virtually all tissues and organs.

Signs and symptoms of MPS 2A include:

• Macrocephaly
• Coarse facies
• Large rounded cheeks
• Thick lips
• Hypertrophic adenoids and tonsils
• Macroglossia
• Hoarse voice
• Short neck
• Retinal degeneration
• Hearing loss
• Recurrent otitis media
• Broad chest
• Ivory-colored papular skin lesions on the upper back and sides of the upper arms [11]
• Protuberant abdomen
• Diarrhea
• Short stature [12]
• Skeletal deformities
• Joint stiffness
• Inguinal or umbilical hernia
• Developmental delay
• Intellectual disability
• Hyperactivity
• Seizures
• Hepatomegaly
• Cardiomyopathy
• Cardiac valve dysplasia
• Carpal tunnel syndrome
• Communicating hydrocephalus
• Pulmonary hypertension
• Hip dysplasia
• Airway obstruction
• Spinal stenosis

The presentation of MPS 2B usually occurs in adolescence or adulthood. Typical signs and symptoms include:

• Hearing impairment
• Joint stiffness
• Coarse face
• Upper airway disease
• Carpal tunnel syndrome
• Communicating hydrocephalus
• Retinal degeneration

Some of these manifestations are seen in a lesser degree in MPS 2B compared to MPS 2A.

The clinical diagnosis requires a thorough patient medical and family history and an examination of the clinical signs. The detection of increased levels of dermatan sulfate and heparan sulfate in the urine is followed by the definitive biochemical diagnosis of MPS 2 through enzyme testing in leukocytes, fibroblasts or plasma. To establish the extent of the disorder, the following tests are recommended:

• Echocardiogram
• Pulmonary function testing [13]
• Sleep study 
• Hearing test
• Nerve conduction velocity for carpal tunnel syndrome
• CT or MRI of the brain stem and cervical spine and lumbar puncture to assess for hydrocephalus and spinal cord compression
• Eye examination with slit lamp to assess visual acuity and corneal and retinal disease
• Developmental assessment

Molecular genetic testing is usually not needed to establish a diagnosis.

At this time, there is no curative treatment of MPS 2. The relevant enzyme can be administered to patients as enzyme replacement therapy and initiation should be done as early as possible [14] [15]. Bone marrow transplantation is another treatment modality [16] [17]. Cranial shunting should be performed in case of hydrocephalus. Hernia repair, carpal tunnel release, tonsillectomy and adenoidectomy, positive pressure ventilation or tracheostomy may be required. Cardiac valve or hip replacement may be necessary over the course of the disease. Developmental, physical, and occupational therapy are often beneficial. A multidisciplinary team approach is important in the management of MPS 2.

Affected individuals appear normal at birth, and age at presentation and progression of the disease vary. In MPS 2A life expectancy is markedly reduced and death frequently occurs in the first or second decade of life, usually due to respiratory or cardiac disease. In the milder form, patients may survive into adulthood, and their intelligence is frequently not affected.

The mucopolysaccharidoses are a group of inherited metabolic disorders caused by genetic defects that lead to the the absence or deficiency of one of the lysosomal hydrolases required for the degradation of glycosaminoglycans. Mucopolysaccharidosis type II is caused by a deficiency of iduronate sulfatase, which normally cleaves a sulfate group from the glycosaminoglycans dermatan sulfate and heparan sulfate. The undegraded glycosaminoglycans accumulate within the lysosomes of various organs and tissues, resulting in their dysfunction, producing a wide variety of progressive symptoms [6].

The incidence of the disorder varies. Schaap and Bach reported an incidence of 1 case per 34,000 males in Israel [7]. Young and Harper estimated the frequency of the disorder in the United Kingdom as about 1 in 132,000 male births [8]. 1 case per 111,000 was found in British Columbia [9]. Studies from Germany and the Netherlands reported an incidence of 1 case per 77,000 male births [10]. The severe form, MPS 2A, appears usually in children aged 2-4 years, while the mild form is frequently diagnosed later. Although this X-linked recessive condition occurs almost exclusively in males, it has also been reported to affect a small group of female individuals.

Mucopolysaccharidosis type II is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate sulfatase. This enzyme cleaves O-linked sulphate moieties from the glycosaminoglycans dermatan sulfate and heparan sulfate in the first step of their degradative pathway. The clinical phenotype of the condition is caused by progressive accumulation of undegraded glycosaminoglycans in nearly all cell types, tissues and organs.

Oropharyngeal and tracheobronchial deposition of glycosaminoglycans results in airway obstruction due to macroglossia, supraglottic narrowing, and tracheomalacia. In the course of the disease, also pulmonary restriction secondary to thoracic skeletal manifestations occurs. Valvular heart leaflets become dysfunctional due to glycosaminoglycan deposition, cardiomyopathy develops and, in conjunction with respiratory disorders, pulmonary hypertension occurs. Bone and joint involvement leads to skeletal deformities and joint stiffness. Central nervous system involvement depends on the form and may include learning difficulties and psychomotor regression. Communicating hydrocephalus can also be present and further contribute to neurological deterioration.

Carrier-testing for individuals and families at risk is available.

Mucopolysaccharidosis type II (MPS 2), also known as Hunter syndrome or Iduronate 2-Sulfatase Deficiency, is an inherited metabolic disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, characterized by accumulation of glycosaminoglycans (GAG). The location of the causative gene is Xq28 and more than 300 mutations have been reported to cause the disorder. It is an X-linked recessive condition and expected to be found in males, but on rare occasions, affected females have been reported. Two types of MPS 2 exist, the severe form MPS 2A and the milder form MPS 2B [1] [2].

Mucopolysaccharidosis type II is a multisystem disorder and symptoms include coarse face, short stature, skeletal abnormalities, recurrent infections, cardiomyopathy, hepatomegaly, umbilical and inguinal hernia, diarrhea, developmental delay, and intellectual disability [2]. To establish a diagnosis, the detection of increased levels of dermatan sulfate and heparan sulfate in the urine is followed by the definitive biochemical diagnosis of MPS 2 through enzyme testing in leukocytes, fibroblasts or plasma [3] [4] [5]. Molecular genetic testing may also be useful. Enzyme replacement therapy (ERT), bone marrow transplantation and management of the complications are the main treatment options.

Mucopolysaccharidosis type II (MPS 2), also known as Hunter syndrome, I2S deficiency or Iduronate 2-sulfatase deficiency, is a progressive, inherited condition that affects many different organs and occurs almost only in males. At birth, affected individuals do not have any symptoms. They develop either in childhood or adolesense, because there are two types of MPS 2.

Common signs and symptoms include a large head, full lips, large rounded cheeks, a broad nose, hoarse voice and an enlarged tongue (macroglossia). Upper respiratory infections and sleep apnea are frequent. Hydrocephalus, an enlarged liver and spleen and hernias occur often. Most patients with MPS 2 have progressive hearing loss and recurrent infections of the middle ear. Skeletal irregularities, vision problems, heart problems, diarrhea, joint stiffness, stunted growth and delayed development may be present. The more severe type of MPS 2 is characterized by a decline in intellectual function and a more rapid progression.

The diagnosis can be made by examination of urine and blood, a genetic analysis can confirm it. The treatment focuses on managing signs and symptoms and depends also on the organs affected and the form of the disease. Intravenous enzyme replacement therapy (ERT) has been shown to alleviate symptoms.

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