Understanding MPS I
MPS I (mucopolysaccharidosis I) is an inherited lysosomal storage disorder caused by a deficiency of alpha-L-iduronidase, a lysosomal enzyme normally required for the breakdown of certain complex carbohydrates known as glycosaminoglycans (GAGs). If the enzyme is not present in sufficient quantities, the normal breakdown of GAGs is incomplete or blocked. The cell is then unable to excrete the carbohydrate residues and they accumulate in the lysosomes of the cell. This accumulation disrupts the cell’s normal functioning and gives rise to the clinical manifestations of the disease.
The incidence of MPS I is estimated to be at about 1 in 115,000 births, according to the National MPS Society. It is inherited in an autosomal recessive manner (both parents must be carriers of the abnormal gene), affects males and females equally, and in most cases, both parents of an affected child are asymptomatic carriers of the disease.
Types of MPS I
Children diagnosed with MPS I have historically been classified into one of three categories based on the severity of their symptoms and rate of disease progression. It has now become clear, however, that there is a wide spectrum of severity in MPS I with much overlap between the categories. The following is a brief overview of the three categories of MPS I:
- Hurler Syndrome:
The most severe form of MPS I is characterized by progressive developmental delay and severe progressive physical problems. Death often occurs before 10 years of age.
- Hurler-Scheie Syndrome:
The intermediate form of MPS I is characterized by normal or near normal intelligence, but more severe physical symptoms than those with Scheie Syndrome.
- Scheie Syndrome:
The attenuated form of MPS I is characterized by normal intelligence, usually normal height, and milder physical problems than Hurler-Scheie. These individuals potentially have a normal life span.
Diagnosis of MPS I
While patients with the most severe form of MPS I are usually diagnosed between ages 1 to 5, those with an intermediate or attenuated form of the disorder may be under diagnosed. Over time, MPS I patients typically get progressively worse, and experience severe disabilities and possibly early death—factors underscoring the importance of early diagnosis.
The following are some of the features associated with MPS I:
- Short stature
- Macrocephaly (large head)
- Coarse facial features
- Progressively coarse facial features
- Delayed or regressed mental development (the severe form)
- Communicating hydrocephalus
- Spinal cord compression
- Carpal tunnel syndrome
- Corneal clouding
- Impaired vision
- Recurrent otitis media
- Impaired hearing
- Recurrent sinopulmonary infections
- Upper airway obstruction
- Sleep apnea
- Reduced pulmonary function
- Cardiac abnormalities and valvular disease
- Umbilical and inguinal hernias
- Reduced joint range of motion
- Dysostosis mutiplex (bone deformities)
- Malaise and reduced endurance
Treatment Options for MPS I
Historically, treatment for MPS I has been limited primarily to palliative care, which addresses the symptoms of the diseases such as respiratory and cardiovascular complications, gastrointestinal symptoms, skeletal manifestations, and loss of vision and hearing. Today, in addition to palliative care, there are other treatment options for consideration. Enzyme replacement therapy with Aldurazyme® (laronidase) is designed to target the underlying cause of the disorder by replacing the missing human enzyme, alpha-L-iduronidase. Aldurazyme is approved in the United States, European Union, and additional countries for the treatment of MPS I. For additional information about this therapy, please visit www.aldurazyme.com. Additionally, bone marrow transplantation may be a treatment option for the most severely affected patients. Broad application of this therapy may be limited by the risks associated with the procedure and the difficulty finding an appropriate donor.
For additional information about MPS I, please visit the following websites and others listed in the Resource Library:
Indication and Fair Balance Statements for Physicians
ALDURAZYME® (laronidase) is indicated for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established.
ALDURAZYME has been shown to improve pulmonary function and walking capacity.
ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.
Important Safety Information
Risk of anaphylaxis.
Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusions. Therefore, appropriate medical support should be readily available when ALDURAZYME is administered. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring.
Life-threatening anaphylactic reactions have been observed in some patients during or up to 3 hours after ALDURAZYME infusions. Reactions have included: respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, airway obstruction, hypoxia, hypotension, bradycardia, and urticaria. Interventions have included: resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and intravenous corticosteroids.
In clinical trials and postmarketing safety experience with ALDURAZYME, approximately 1 percent of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate medical support should be readily available when ALDURAZYME is administered. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation. The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic reaction should be considered.
Patients with an acute illness at the time of ALDURAZYME infusion may be at greater risk for infusion-related reactions. Careful consideration should be given to the patient’s clinical status prior to administration of ALDURAZYME.
Patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion reaction occurs, regardless of pretreatment, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics and/or antihistamines may ameliorate the symptoms.
The most common adverse reactions associated with ALDURAZYME treatment in the clinical studies were upper respiratory tract infection, rash, and injection site reaction The most common adverse reactions requiring intervention were infusion-related reactions involving flushing, fever, headache, and rash.
In postmarketing experience with ALDURAZYME, severe and serious infusion-related reactions have been reported, some of which were life-threatening. The most frequently reported adverse reactions included: chills, vomiting, nausea, arthralgia, diarrhea, tachycardia, abdominal pain, blood pressure increased, and oxygen saturation decreased.
Approximately 91 percent of patients treated with ALDURAZYME in clinical studies were positive for antibodies to laronidase. The clinical significance of antibodies to ALDURAZYME is not known, including the potential for product neutralization. Adverse events should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. ALDURAZYME is available by prescription only. To learn more, please see the full prescribing information including boxed warning, visit www.ALDURAZYME.com or contact Genzyme at 1-800-745-4447.