Mucopolysaccharidosis type II

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a condition that affects many different parts of the body. The condition occurs almost exclusively in boys, although it has been reported in a few girls. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals.

At birth, individuals with MPS II do not display any features of the condition. Between ages 2 and 4, they develop full lips; large, rounded cheeks; a broad nose; and an enlarged tongue (macroglossia). The vocal cords also enlarge, which results in a deep, hoarse voice. Narrowing of the airway causes frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). As the disorder progresses, individuals need medical assistance to keep their airway open.

Many other organs and tissues are affected in people with MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), a short neck, an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Some affected individuals also have distinctive white skin growths that look like pebbles. Most people with this disorder develop hearing loss. Some individuals with MPS II develop problems with the light-sensitive tissue in the back of the eye (retina) and have reduced vision. Carpal tunnel syndrome commonly occurs in children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. The heart is also significantly affected by MPS II, and many individuals develop heart valve problems. Heart valve abnormalities can cause the heart to become enlarged (ventricular hypertrophy) and can eventually lead to abnormalities in the heart's rhythm (arrhythmia) and heart failure.

Children with MPS II grow steadily until about age 5, and then their growth slows and they develop short stature. Individuals with this condition have joint deformities (contractures) that significantly affect mobility. Most people with MPS II also have dysostosis multiplex, which refers to multiple skeletal abnormalities that can be seen on x-rays. Dysostosis multiplex includes a generalized thickening of certain bones, particularly the ribs.

There are two types of MPS II: the neuropathic form, which is more severe, and the non-neuropathic form, which is less severe. While both types affect many different organs and tissues as described above, people with neuropathic MPS II also experience a decline in intellectual function and a more rapid disease progression. Individuals with this form begin to lose basic functional skills (developmentally regress) between the ages of 6 and 8. Their life expectancy is 10 to 20 years. Individuals with non-neuropathic MPS II also have a shortened lifespan, but they typically live into adulthood, and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the IDS gene cause MPS II. The IDS gene provides instructions for producing the I2S enzyme, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name.

IDS gene variants that cause MPS II reduce or completely eliminate the function of the I2S enzyme. Lack of I2S enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS II, are called lysosomal storage disorders.

The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in people with this disorder. Researchers believe that the accumulated GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt the movement of molecules inside the cell. In addition, buildup in lysosomes may trigger the release of molecules called cytokines that stimulate inflammation and may contribute to the progression of MPS II.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that both copies of a gene would be altered, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

MPS II occurs in approximately 1 in 100,000 to 1 in 170,000 males.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal heart morphology · Very frequent (99-80%)

Any structural anomaly of the heart.

Coarse facial features · Very frequent (99-80%)

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Limitation of joint mobility · Very frequent (99-80%)

A reduction in the freedom of movement of one or more joints.

Macrocephaly · Very frequent (99-80%)

Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Short stature · Very frequent (99-80%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Abnormal heart valve morphology · Frequent (79-30%)

Any structural abnormality of a cardiac valve.

Atypical behavior · Frequent (79-30%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Chronic diarrhea · Frequent (79-30%)

The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.

Other findings in the same source

From: Orphanet

Additional reported features include Cognitive impairment (Frequent (79-30%)); Conductive hearing impairment (Frequent (79-30%)); Decreased nerve conduction velocity (Frequent (79-30%)); Dermatan sulfate excretion in urine (Frequent (79-30%)); Developmental regression (Frequent (79-30%)); Enlarged tonsils (Frequent (79-30%)); Flexion contracture of digit (Frequent (79-30%)); Full cheeks (Frequent (79-30%)); Gingival overgrowth (Frequent (79-30%)); Growth delay (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Mucopolysaccharidosis type II is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Mucopolysaccharidosis type II. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.