MUCOPOLYSACCHARIDOSIS TYPE II

Subtype of MUCOPOLYSACCHARIDOSIS

Mucopolissacaridoses (MPS) are genetic diseases classified as lysosomal storage diseases caused by deficiency of enzymes needed for the gradual decrease of glycosaminoglycans (GAGs).

The MPSs are differentiated by association with different types of enzymes, their clinical presentation and age. The mucopolissacaridoses are classified into the following subtypes:

 

MPS II is caused by mutations in the gene that encodes DHS, which is located on chromosome Xq28. This mutation generates a deficiency of iduronate 2-sulfatase (IDS), resulting in storage heparan and dermatan sulfate.

Reports of patients with severe outcome for MPS II have been related to  contiguous gene deletions.

Despite being MPS II a disease with inheritance pattern and X-linked, there are reports of female affected patients.

 

Diagnosis

After an evaluation of the natural history of MPS and established the suspicion of the presence of signs and symptoms, diagnostic confirmation by additional tests may be done as follows:

Determination of glycosaminoglycans:

In the presence of a suspected MPS, the concentration of glycosaminoglycans (GAGs) should be measured in the urine, preferably, one should use the first morning urine (more concentrated) in terms of low concentrations of urinary GAGs present in more dilute urine, especially for MPS III and IV.

Enzymatic Analysis:

The definitive diagnosis with plasma GAG showing high levels can be established to measure the activity of the enzyme iduronate 2-sulfatase (IDS) in plasma, leukocytes (more sensitive than plasma) or fibroblasts through a skin biopsy.

Molecular Analysis:

A molecular analyzes can be performed when the mutations are known.

Prenatal Analysis:

The prenatal analysis can be done according to the enzymatic assay suggested by the FDA and chorion villus biopsy (used for method avoids the need of tissue culture by providing results more rapidly than in culture amniocytes.).

The activity of the enzyme can also be measured in cultured fibroblasts obtained by amniocentesis.

 

Enzyme replacement therapy (ERT)

Before using the medicine Idursulfase, the label should be consulted. The contents described in Datagenno may not contain all the side effects and risks described in the instructions of the manufacturer, so the label of the medicine should always be consulted prior to its use.

Enzyme replacement therapies (ERT) are mainly done with Idursulfase.

Dosage: patients 5 years old or more is indicated 0.5 mg / kg every 7 days, the infusion time is 1-3 hours, always using the infusion pump and 0.2 micron filter in the tubing from the serum. The drug should be reconstituted with dilution in 100 ml of 0.9% solution sodium chloride and used within 3 hours of reconstitution, the total time of reconstitution by the end of infusion does not exceed 24 hours.

The speed of initial infusion of 8 ml / hour for the first 15 minutes once a well tolerated, can increase the rate of infusion every 15 minutes reaching a maximum speed of 100ml/hora. The infusion should be stopped if adverse effects appear, the effects should be treated and the infusion can be resumed 10 minutes after the improvement of the symptoms.

It may be necessary a higher infusion time due to possible adverse side  effects, however, total infusion time must not exceed 8 hours.

 

Monitoring of patients on ERT

Adverse effects of ERT

The most common effects related to the use of Idursulfase are infusion reactions, headache, fever, allergic skin reactions (rash, erythema, urticaria, pruritus) and increased blood pressure. Studies show that frequency of infusion-related reactions with the drug decreased over time during treatment.

Severe reactions have been described episodes of falling oxygen levels, a case of: heart rhythm disorder, pulmonary embolism, is cyan, respiratory failure, infection and joint pain.

The use of corticosteroids and antihistamines can be done to control of adverse reactions.

Anaphylactic reactions were life-threatening in some patients during the infusion of Idursulfase. Therefore, one must have available medical support suitable for administration Idursulfase.

 

Counter indications

Idursulfase is contraindicated for Individuals hypersensitive to Idursulfase or any other ingredients. There are no studies that evaluated the safety of Idursulfase in patients under 5 years of age, so their safety and effectiveness can not be guaranteed.

Precautions related to adverse side effects:

Severe reactions anaphylaxis and life threatening for the patient may occur even late reactions within 24h after the initial reaction.

The Idursulfase should be administered with caution in patients with ongoing Respiratory failure or acute respiratory illness.

During the infusions medical support should be available at all times.

Antibody formation: about 50% of patients with the possibility of an increased incidence when compared to the infusion effects.