As with many medical conditions, diagnosis of MPS I starts with clinical suspicion. Because MPS I generally affects many organ systems and can present in a variety of ways, diagnosis may require collaboration and communication between geneticists, neurologists, pediatricians, developmental specialists, surgeons, cardiologists, gastroenterologists, physical therapists, and primary care providers. Symptoms, by specialty, that may lead to clinical suspicion include:[1][2][3]

Primary Care Providers

  • recurrent otitis media or “glue ear”
  • chronic rhinitis
  • abdominal protuberance
  • gibbus deformity
  • joint restriction
  • abnormal gait
  • hand/wrist pain
  • above normal growth or head size


  • recurrent upper respiratory tract infections
  • recurrent otitis media or “glue ear”
  • developmental delay
  • hepatosplenomegaly
  • joint restriction
  • gibbus deformity
  • coarse facial features


  • recurrent otitis media or “glue ear” requiring tube placement
  • chronic rhinitis
  • snoring

General/Pediatric Surgeons

  • inguinal and umbilical hernia
  • carpal tunnel syndrome


  • corneal clouding
  • retinal degeneration

Findings in MPS I may overlap with those of other lysosomal storage disorders, particularly other mucopolysaccharide diseases and multiple sulfatase deficiency. Detailed clinical findings and biochemical testing are necessary for their differentiation. There are some early clinical signs and symptoms, which alone are not diagnostic, but may warrant more definitive testing. Although these findings at presentation will vary with the severity of the disorder, MPS I should be suspected in individuals with coarse facial features, hepatosplenomegaly, and characteristic skeletal, joint, or ocular findings.

Confirming a Diagnosis

Analysis of urinary glycosaminoglycans (heparan sulfate and dermatan sulfate) was the first method available for diagnosis of MPS I and may still be used as a preliminary investigative test.

Today, diagnosing relies on demonstrating a deficiency of the lysosomal enzyme alpha-L-iduronidase using enzyme assays specific for alpha-L-iduronidase.[4][5][6] This enzyme activity may be measured in most tissues; however, a diagnosis is usually made using peripheral blood leukocytes, plasma, or cultured fibroblasts.

Prenatal Diagnosis

Prenatal diagnosis is routinely carried out on cultured cells from amniotic fluid or chorionic villus biopsies using the same enzyme assay that is used for monitoring alpha-L-iduronidase in cultured fibroblasts or leukocytes.

Genotype-Phenotype Correlations

Genotype-phenotype correlations in MPS I are complex and further research is required before they may be clinically useful.

Carrier Testing

Carrier testing is a service often requested by MPS I families. However, to date, the analysis of alpha-L-iduronidase enzyme activity does not provide definitive carrier information. This is related to the fact that there is considerable overlap between the normal and heterozygous ranges[6] and that pseudodeficiency of alpha-L-iduronidase has been reported. Thus, there may be issues associated with interpreting results of enzyme levels in the general population.

Carrier testing is most often performed if the family mutation is known. However, the large number of mutations that underlie MPS I and the technologies available to assess gene mutations do not currently allow for routine carrier detection by molecular methods.[6] The value of carrier testing for the purpose of identifying couples who may be at risk of having an affected child is also limited. This is because, even if one can accurately determine the carrier status of a relative of an MPS I patient, the determination of the carrier status of the unrelated spouse is difficult.

Molecular Genetic Testing and Molecular Diagnosis

When considering DNA-based tests one must take into account the great heterogeneity of mutations underlying MPS I. Mutant alleles need to be identified for the specific family before molecular diagnosis can be undertaken for members at risk. Many patients will likely be compound heterozygotes; thus both mutant alleles must be known for carrier testing to be helpful for the family. Once the mutant allele(s) are identified (either by the mutation itself, or by an intragenic polymorphism), molecular diagnosis may become easier and require less DNA material, which is important for prenatal testing.[6] However, the large number of private mutations may keep mutation analysis impractical for some families. Until mutation analysis becomes more readily available, diagnosis should be established by enzyme assay. DNA-based diagnosis is the only definitive test for determining carrier status but will likely have limited value in individuals who are at low risk of being carriers.



ALDURAZYME® (laronidase) is a prescription only medication 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

WARNING: 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.

Anaphylaxis and severe allergic reactions have been observed in patients during or up to 3 hours after ALDURAZYME infusions. Some of these reactions were life-threatening and included respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, obstructive airways disorder, hypoxia, hypotension, bradycardia, and urticaria. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion of ALDURAZYME and initiate appropriate treatment. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased prevalence of coronary artery disease in these patients. Interventions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.

In clinical studies and postmarketing safety experience with ALDURAZYME, approximately 1% 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. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.

Patients with an acute febrile or respiratory illness at the time of ALDURAZYME infusion may be at greater risk for infusion reactions. Careful consideration should be given to the patient’s clinical status prior to administration of ALDURAZYME and consider delaying ALDURAZYME infusion.

Sleep apnea is common in MPS I patients. Evaluation of airway patency should be considered prior to initiation of treatment with ALDURAZYME. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction or extreme drowsiness/sleep induced by antihistamine use.

Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload or patients with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status during infusions. Appropriate medical support and monitoring measures should be readily available during ALDURAZYME infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient.

Because of the potential for infusion reactions, patients should receive antipyretics and/or antihistamines prior to infusion. If an infusion-related reaction occurs, regardless of pre-treatment, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms.

The most serious adverse reactions reported with ALDURAZYME treatment during clinical trials were anaphylactic and allergic reactions.

In a 26-week, placebo-controlled clinical trial in patients 6 years and older, the most commonly reported infusion reactions regardless of treatment group were flushing, pyrexia, headache, and rash. Flushing occurred in 5 patients (23%) receiving ALDURAZYME; the other reactions were less frequent. Less common infusion reactions included angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting, back pain, and cough. Other reported adverse reactions included bronchospasm, dyspnea, urticaria, and pruritus. In the open-label, uncontrolled extension phase of this clinical trial, the infusion reactions were similar, but also included abdominal pain or discomfort and injection site reaction. Less commonly reported infusion reactions included nausea, diarrhea, feeling hot or cold, vomiting, pruritus, arthralgia and urticaria. Additional common adverse reactions included, back pain and musculoskeletal pain.

In an open-label, uncontrolled clinical trial in patients 6 years and younger who received ALDURAZYME treatment for up to 52 weeks, the most commonly reported serious adverse events (regardless of relationship) in patients 6 years and younger, were otitis media (20%), and central venous catherization required for ALDURAZYME infusion (15%). The most commonly reported adverse reactions in patients 6 years and younger were infusion reactions reported in 35% (7 of 20) of patients and included pyrexia (30%), chills (20%), blood pressure increased (10%), tachycardia (10%), and oxygen saturation decreased (10%). Other commonly reported infusion reactions occurring in ≥5% of patients were pallor, tremor, respiratory distress, wheezing, crepitations (pulmonary), pruritus, and rash.

In postmarketing experience with ALDURAZYME, severe and serious infusion reactions have been reported, some of which were life-threatening, including anaphylactic shock. Adverse reactions resulting in death reported in the postmarketing setting with ALDURAZYME treatment included cardio-respiratory arrest, respiratory failure, cardiac failure, and pneumonia. These events have been reported in MPS I patients with significant underlying disease. Additional common adverse reactions included erythema and cyanosis. There have been a small number of reports of extravasation in patients treated with ALDURAZYME. There have been no reports of tissue necrosis associated with extravasation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In clinical trials, 99 of 102 patients (97%) treated with ALDURAZYME were positive for IgG antibodies to ALDURAZYME. In the 2 trials of patients 6 years and older, 9 patients who experienced severe infusion reactions were tested for ALDURAZYME-specific IgE antibodies and complement activation. One of the nine patients had an anaphylactic reaction consisting of urticaria and airway obstruction and tested positive for both ALDURAZYME-specific IgE binding antibodies and complement activation. In the postmarketing setting, approximately 1% of patients experienced severe or serious infusion-allergic reactions and tested positive for IgE. Of these IgE-positive patients, some have discontinued treatment, but some have been successfully re-challenged. The clinical significance of antibodies to ALDURAZYME, including the potential for product neutralization, is not known.

Adverse events should be reported promptly to Sanofi Genzyme Medical Information at 800-745-4447, option 2.

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

ALDURAZYME is available by prescription only. To learn more, please see the Full Prescribing Information including Boxed Warning (PDF), visit www.ALDURAZYME.com or contact Sanofi Genzyme at 1-800-745-4447, option 2.


  1. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135. Accessed April 11, 2017.
  2. Cleary MA, Wraith JE. The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). Acta Paediatr. 1995;84:337-339.
  3. Scheie HG, Hambrick GW, Barness LA. A newly recognized forme fruste of Hurler’s disease (Gargoylism). American Journal of Ophthalmology 1962;53(5):753-69.
  4. Hall CW, Liebaers I, Di Natale P, Neufeld EF. Enzymatic diagnosis of the genetic mucopolysaccharide storage disorders. Methods Enzymol 1978;50:439-456.
  5. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135. Accessed April 11, 2017.
  6. Neufeld EF, Muenzer J. The Mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135. Accessed April 11, 2017.

Resources & Support

Information on MPS I disease is limited because of its rarity. Learn more about MPS I Registry, a global resource dedicated to improving the understanding of MPS I disease.

Complete Prescribing Information

View full prescribing information including boxed warning.