Clinical UM Guideline

 

Subject: Laronidase (Aldurazyme®)
Guideline #:  CG-DRUG-58 Publish Date:    12/27/2017
Status: Reviewed Last Review Date:    11/02/2017

Description

This document addresses the clinical indications for laronidase (Aldurazyme, BioMarin Pharmaceutical Inc., Novato, CA and Genzyme Corporation, Cambridge, MA), a polymorphic variant of the human enzyme, alpha-L-iduronidase. Laronidase is an enzyme replacement therapy (ERT) approved by the U.S. Food and Drug Administration (FDA) for the treatment of individuals with Mucopolysaccharidosis I, including Hurler syndrome, Hurler-Scheie syndrome, as well as those with Scheie syndrome who have moderate to severe symptoms.

Clinical Indications

Medically Necessary:

Laronidase is considered medically necessary for the treatment of an individual with Mucopolysaccharidosis I (MPS I) when the following criteria are met:

  1. Diagnosis of any of the following MPS I syndromes:
    1. Hurler syndrome; or
    2. Hurler-Scheie syndrome; or
    3. Scheie syndrome, moderate to severe manifestations including any of the following:
      1. Cardiac valve abnormalities (such as aortic or mitral valve regurgitation, with or without insufficiency or stenosis); or
      2. Corneal clouding, open-angle glaucoma, and retinal degeneration, progressive; or
      3. Craniofacial or growth retardation; or
      4. Frequent, moderate to severe upper respiratory infections; or
      5. Hepatosplenomegaly; or
      6. Hernias (such as hiatal, inguinal, or umbilical); or
      7. Neurological symptoms resulting from cervical instability or cervical spinal cord compression; or
      8. Skeletal and joint involvement, progressive (such as, arthropathy, back pain, joint stiffness, lumbar spondylolisthesis, lumbar spinal compression, osteopenia, or osteoporosis); and  
  2. Diagnosis is confirmed by either of the following:
    1. Documented deficiency in alpha-L-iduronidase enzyme activity of less than 10% of the lower limit of normal range as measured in fibroblasts or leukocytes; or
    2. Documented alpha-L-iduronidase gene sequencing.

Not Medically Necessary:

Laronidase is considered not medically necessary for all other indications, including the treatment of an individual with the Scheie form of MPS I who has mild symptoms.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J1931

Injection, laronidase, 0.1 mg (Aldurazyme)

S9357

Home infusion therapy, enzyme replacement intravenous therapy, (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

 

 

ICD-10 Diagnosis

 

E76.01

Hurler’s syndrome

E76.02

Hurler-Scheie syndrome

E76.03

Scheie’s syndrome

Discussion/General Information

Description of the Condition

MPS I is an inherited autosomal recessive lysosomal storage disease caused by a deficiency of α-L-iduronidase, a lysosomal enzyme required for the catabolism (breakdown) of complex carbohydrates known as glycosaminoglycans (GAGs). Reduced or absent L-iduronidase activity blocks the degradation of GAG substrates dermatan sulfate and heparin sulfate and leads to accumulation of these substrates throughout the body, resulting in progressive damage to a broad range of tissues (Aldurazyme Product Information [PI] Label, 2013). MPS I has historically been divided into three broad groups based on severity of symptoms: Hurler syndrome (MPS 1-H, severe), Hurler-Scheie syndrome (MPS I-HS, intermediate), and Scheie syndrome (MPS I-S, attenuated). MPS I is now viewed as a continuous spectrum of disease, with the most severely affected individual on one end, the less severely affected (attenuated) on the other end, and a wide range of different severities in between. The population frequency of MPS I is estimated to be approximately 1 in 100,000 births, with MPS I-H the most common and MPS I-S the rarest of the subtypes (National Institute of Neurological Disorders and Stroke [NINDS], 2017).

Children with MPS I inherit a defective gene from both their mother and father with symptoms generally beginning between ages 3 and 8. In the most severe form of MPS I, developmental delay is evident by the end of the first year, and children usually stop developing between ages 2 and 4. Following this is progressive mental decline and loss of physical skills. Children with severe MPS I often die before age 10 from obstructive airway disease, respiratory infections, or cardiac complications. Although symptoms generally begin to appear after age 5 in children with attenuated MPS I, the diagnosis is most commonly made after age 10. At the opposite end of the spectrum, children with Scheie syndrome are intellectually normal and may have a normal life span; however, many will become disabled due to degenerative bony disease, corneal opacity and valvular heart disease and longevity is dependent upon the particular syndrome (Jameson, 2016; NINDS, 2017). In a review article, Thomas and colleagues (2010) state:

Using natural history data from the uniquely large population of 78 Scheie patients enrolled in the MPS I Registry, we characterized the onset and prevalence of clinical manifestations and explored reasons for delayed diagnosis of the disease. Median patient age was 17.5 years; 46% of the patients were male, and 88% were Caucasian. Of 25 MPS I-related clinical features, cardiac valve abnormalities, joint contractures, and corneal clouding were each reported by > 80% and all three by 53% of patients. Carpal tunnel syndrome, hernia, coarse facial features, and hepatomegaly were each reported by >5 0% of patients. Age at onset of the clinical features varied widely between individuals, but the median age at onset was 3 years for hernia and between 5 and 12 years for most features, including coarse facial features, hepatomegaly, joint contractures, bone deformities, cardiac valve abnormalities, cognitive impairment, and corneal clouding. Carpal tunnel syndrome, cardiomyopathy, and myelopathy arose more commonly during adolescence or adulthood…Scheie syndrome usually emerges during childhood, and recognition of attenuated MPS I requires awareness of the multisystemic disease manifestations and their diverse presentation.

The clinical manifestations of MPS I syndromes may include inhibited growth (short stature), developmental delay/learning disabilities, abnormal gait (especially toe walking), abdominal protrudence due to hepatosplenomegaly, hernias, impaired vision (corneal clouding), hearing loss, impaired cardiac and pulmonary function (including frequent respiratory infections, noisy breathing, heart murmur), skeletal malformations, and often, neurological abnormalities (including mental dysfunction). The most suggestive rheumatological feature of MPS I is development of joint pain and joint contractures at an early age without concomitant inflammation. Other common bone and joint feature (subtle or overt) include claw hand, spinal deformity (gibbus, kyphosis, lordosis, and scoliosis) and radiologic evidence of dysostosis multiplex. Distinguishing clinical features of MPS I relative to other MPS disorders include progressive corneal clouding and cognitive impairment (but rarely with overt behavioral issues) (Lehman, 2011; NINDS, 2017).

Diagnosis of the Condition

A diagnostic workup in an individual with MPS I typically demonstrates elevated levels of urinary GAG (that is, MPS quantitative urine) and increased amounts of both dermatan and heparan sulfate detected on thin-layer chromatography. Reduced or absent activity of α-L-iduronidase in blood spots, fibroblasts, leukocytes, or whole blood can confirm a diagnosis of MPS I; however, enzymatic testing is not reliable for carrier detection. Molecular sequence analysis of the IDUA gene allows for detection of the disease-causing mutation in affected individuals and subsequent carrier detection in relatives. To date, a clear genotype-phenotype correlation has not been established.

In a GeneReviews®, Clarke (2016) states that MPS I should be suspected in individuals with the following suggestive clinical and supportive laboratory findings:

Clinical findings

Supportive laboratory findings
Analysis of urinary GAG (i.e., heparan and dermatan sulfate) may be quantitative (measurement of total urinary uronic acid) or qualitative (GAG electrophoresis to analyze the specific GAGs excreted).

To establish a definitive diagnosis of MPS I (Clarke, 2016), the following molecular genetic testing is recommended:

The diagnosis of MPS I is established in a proband with the suggestive clinical and laboratory findings (above) and either identification of biallelic pathogenic variants in IDUA on molecular genetic testing or detection of deficient activity of the lysosomal enzyme α-L-iduronidase. Molecular testing approaches can include single-gene testing and use of a multi-gene panel.

The detection rate for pathogenic variants by sequence analysis of the IDUA gene in 85 individuals (Beesley, 2001) and 102 individuals (Bertola, 2011) with MPS I was reported at 95%-97% (that is, the proportion of probands with pathogenic variants detectable by sequence analysis alone).

Clinical Safety and Effectiveness of Laronidase for MPS I Syndromes

Laronidase therapy in individuals with MPS I is intended to provide exogenous enzyme for uptake into lysosomes and increase the catabolism of GAG. The effects of intravenously (IV) administering laronidase on cells within the central nervous system (CNS) cannot be inferred from activity in sites outside the CNS. The ability of laronidase to cross the blood brain barrier has not been evaluated in animal models or clinical studies (Aldurazyme PI Label, 2013).

The American College of Medical Genetics (ACMG) publication on the diagnosis and management of lysosomal storage diseases addresses several syndromes including MPS I. The ACMG guidelines describe how weekly treatment with 0.58 mg/kg/dose of laronidase improved forced vital capacity (FVC), reduced symptoms of airway obstruction, and exercise tolerance increased as demonstrated by improved 6-minute walk distance (6MWD) test results. Liver and spleen volumes were reduced to near normal levels and both weight and height growth trended towards normalization (Wang, 2011).

In 2003, the FDA approved laronidase as an orphan drug for use in the treatment of individuals diagnosed with MPS I with Hurler or Hurler-Scheie syndrome and for those with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected individuals with the Scheie form have not been established. Laronidase has been shown to improve pulmonary function and walking capacity. Laronidase has not been evaluated for effects on the CNS manifestations of the disorder (Aldurazyme PI Label, 2013; Wang, 2011).

In a 26 week, randomized, double-blind, placebo-controlled phase 3 study (n=45, age range, 6 to 43 years) laronidase improved FVC and the 6MWD in individuals with Hurler or Hurler-Scheie forms of MPS I (Wraith, 2004). At baseline, all participants had a percent of predicted normal FVC of 77% or less with a mean baseline percent of predicted normal FVC of 48% ± 15% in the laronidase arm and 54% ± 16 % in the placebo arm. Laronidase was administered 0.58 mg/kg of body weight once weekly (n=22) or placebo (n=23) once weekly. The mean baseline 6MWD was 319 ± 131 meters and 367 ± 114 meters. Relative to baseline, after 26 weeks of either laronidase or placebo once weekly. Laronidase significantly improved FVC compared with placebo (mean FVC change, 1% ± 7% vs. -3% ± 7%, respectively; mean difference, 4%; mean difference, 2%; 95% confidence [CI], 0.4% to 7%; p=0.02). At 26 weeks, laronidase improved 6MWD from baseline, but the improvement was not statistically significant (mean 6MWD change from baseline, 28 meters vs. -11 meters, respectively; mean difference, 38 meters; median difference, 39 meters, 95% CI, -2 to 79; p=0.07). Although liver size and urinary GAG levels were decreased among participants receiving laronidase compared with placebo, no laronidase-treated participants achieved the normal range for urinary GAG levels over the 26-week study period. In the 4-year, open-label, phase 3 extension study (Clarke, 2009), long-term treatment with laronidase maintained an improvement in 6MWD over an additional 182 weeks in participants with Hurler or Hurler-Scheie forms of MPS I. Mean urinary GAG level decreases reported at 182 weeks were similar to those reported after 26 weeks.

In a phase 2 trial, Kakkis and colleagues (2001) reported that laronidase infusions were associated with clinical and biochemical improvements in a small cohort of children, adolescents, and a single adult with MPS I. A total of 10 participants (n=9, 5 to 17 years; n=1, 22 years) with MPS I (predominately Hurler-Scheie syndrome) experienced significant reductions in hepatosplenomegaly and urinary GAG excretion (63%, mean reduction from baseline), and improvement in some signs and symptoms during one year of treatment with weekly laronidase. There was a significant increase reported in the rate of growth in height (2.8 to 5.15 cm/year) and weight (1.7 to 3.8 kg/year) in prepubertal participants. The degree of elbow extension and shoulder flexion increased significantly from baseline in evaluable participants, however, knee extension was unaffected. A trend towards improvement of airway function and endurance/performance of daily activities was reported, but the investigators did not perform statistical analyses. Cardiac function improved subjectively (1 or 2 New York Heart Association classes), but this improvement was not confirmed by echocardiography. No improvement was reported in corneal clouding. A limitation of this study was the lack of a control group to confirm these outcomes.

The safety and effectiveness of laronidase in children younger than 5 years of age were reported in a prospective, open-label, uncontrolled, multinational study (n=20) of 16 children with Hurler syndrome and 4 children with Hurler-Scheie syndrome (Wraith, 2007). Clinical improvements in hepatomegaly, left ventricular hypertrophy, and apnea/hypopnea index were noted in 94% of children with weekly laronidase at week 52. Four children underwent dosage increases for the last 26 weeks because of elevated urinary GAG levels at week 22. The mean urine GAG level declined by approximately 50% by 13 weeks and was sustained thereafter. No participant reached the normal range for urinary GAG levels for the study duration. The change in urinary GAG levels in children 6 years or younger was similar to the urinary GAG changes observed in older individuals (6 through 43 years of age).

Laraway and colleagues (2016) retrospectively evaluated the long-term outcomes of laronidase therapy in 35 individuals with attenuated MPS I (Hurler-Scheie and Scheie syndrome) for up to 10 years (mean follow-up, 6.1 years) following initiation of therapy. Case notes, laboratory results and data from clinical trials was analyzed for urinary GAG levels, FVC, 6MWD test, height-for-age Z score, cardiac valve function, corneal clouding, and visual acuity. Of the 35 individuals, one discontinued laronidase after 1 year (declined weekly intravenous infusions) and 3 individuals died during follow-up. Baseline urinary GAG data were available for 91% (32 of 35) individuals. Mean urinary GAG levels decreased by more than 50% from baseline within 6 months of laronidase therapy regardless of age at initiation with reductions remaining between 50% and 90% of baseline values throughout follow-up. The percentage of reduction from baseline was statistically significant (p<0.001) at all time points (6 months to 7 years). There were no statistically significant changes in mean FVC, 6MWD test, or height-for-age Z score. At the last assessment, disease remained stable in mitral and aortic valve function (65%, 22 of 34 individuals), corneal clouding (78%, 18 of 23 individuals), and visual acuity (33%, 8 of 24 individuals) with some improvement in visual acuity in 42% (10 of 24) of individuals. Individuals of younger age who initiated treatment at less than 10 years of age maintained disease measures (that is, FVC, 6MWD test, and height) closer to norms than those individuals aged 10 or older at treatment initiation. Fewer children aged less than 10 years at treatment initiation experienced mitral and aortic valve deterioration compared with those aged 10 years or older (14% vs. 40%, respectively). Limitations of this study include difficulties in accurately assessing cardiac function by echocardiography, and only subjective and non-standardized assessment of stenosis/regurgitation was reported. Other limitations include heterogeneity of the study population, which may have affected outcome measures known to be affected by demographics such as age, sex and ethnicity in individuals with MPS I.

Perez-Lopez and colleagues (2017) performed a systematic review of the evaluable randomized trials or observation studies to assess effectiveness variables modified in individuals with MPS I who initiated laronidase as adults (≥ 18 years). A meta-analysis of studies evaluating the same effectiveness outcomes was performed and the evidence was rated according to GRADE criteria. Heterogeneity was assessed by the Chi-squared test and the I-squared statistic. Case reports were excluded from meta-analysis and their main outcomes were evaluated separately. The primary outcome was the reduction of urine GAG levels in terms of: 1) percentage of individuals with reduction in baseline urine GAG levels; and 2) percentage of individuals with normalization of urine GAG levels. A total of 19 studies and 12 case reports were reviewed. Use of laronidase resulted in decreased urine GAG levels (high evidence) and liver volume (high evidence), improved 6MWD test (moderate evidence) and increased blood anti-laronidase antibody levels (high evidence). There was no conclusive results (low or very low evidence) regarding improvement/stabilization of respiratory function, change in shoulder flexion, cardiac improvement/stabilization, improvement in symptoms of nocturnal hypoventilation and sleep apnea, improvement in quality of life, visual acuity, otolaryngologic function, bone mineral density or effectiveness of intrathecal therapy. Limitations of this analysis include lack of specific studies in the target population (that is, laronidase initiated at ≥ 18 years) and very few randomized clinical trials; thus, data was extracted mainly from subgroup analyses of observational studies that included all MPS I subjects. There was also significant heterogeneity between study designs and the evaluated clinical outcomes; however, no publication bias was observed in reporting of positive outcomes of laronidase therapy (vs. no effect) in the evaluated studies.

In the clinical studies and post-marketing safety experience with laronidase, approximately 1% of participants experienced severe or serious allergic reactions. In participants with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. The most commonly reported infusion reactions occurring in at least 10% of infants and children 6 months of age and older were pyrexia, chills, blood pressure increased, tachycardia, and oxygen saturation decreased. The development of antibodies against exogenous enzyme did not appear to correlate with infusion reactions or response to laronidase. The most frequently occurring adverse reactions occurring in at least 10% of children 6 years and older are rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, and poor venous access. It has been observed that most individuals develop antibodies by week 12 of laronidase infusion; therefore, individuals are routinely premedicated one hour before the infusion begins with antihistamines and antipyretics (Aldurazyme PI Label, 2013).

FDA Black Box Warnings and Additional Information for Use of Laronidase

The PI Label (Aldurazyme, 2013) for laronidase includes the following Black Box warning:

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.

Dosing Information and Use in Specific Populations

Warnings and Precautions

Definitions

6-minute walk distance (6MWD) test: A standardized test that measures how far a person can walk on a hard, flat surface in 6 minutes and has been used to assess endurance in several MPS syndromes (ATS, 2002).

Dysostosis multiplex: A complex of multiple skeletal abnormalities affecting the bones of the face, spine, ribs and extremities.

Enzyme replacement therapy (ERT): A treatment provided via intravenous infusion to provide enzymes in an individual unable to make sufficient amounts of that enzyme on their own.

Forced vital capacity (FVC): A measurement of the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible; FVC is used assess the presence and severity of lung diseases.

Hurler syndrome (MPS I-H, severe): The most common and severe subtype of MPS I syndrome. Symptoms of MPS I-H are reported as follows (Wang, 2011):

Hurler-Scheie syndrome (MPS I-HS, intermediate): Also classified as combined “intermediate/attenuated” MPS I-HS. Symptoms of MPS I-HS are reported as follows (Wang, 2011):

Molecular genetic testing: Testing that involves the analysis of deoxyribonucleic acid (DNA), either through linkage analysis, sequencing, or one of several methods of mutation detection.

Mutation: A permanent, transmissible change in genetic material.

Proband: A term used in medical genetics to refer to the first affected family member with a known pathogenic genetic mutation.

Scheie syndrome (MPS I-S, attenuated): The rarest subtype of MPS I syndrome which leads to difficulty in developing characteristic phenotypic descriptions. Symptoms of MPS I-S are reported as follows, and may be mild, or moderate to severe (Wang, 2011):

Sequence analysis: Process by which the nucleotide sequence is determined for a segment of DNA. Also referred to as gene sequencing.

References

Peer Reviewed Publications:

  1. Beesley CE, Meaney CA, Greenland G, et al. Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum Genet. 2001; 109:503-511.
  2. Bertola F, Filocamo M, Casati G, et al. IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. Hum Mutat. 2011; 32:E2189-E2210.
  3. Clarke LA, Wraith JE, Beck M, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009; 123(1):229-240.
  4. Horovitz DD, Acosta AX, Giugliani R, et al. Alternative laronidase dose regimen for patients with mucopolysaccharidosis I: a multinational, retrospective, chart review case series. Orphanet J Rare Dis. 2016; 11(1):51.
  5. Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001; 344(3):182-188.
  6. Laraway S, Mercer J, Jameson E, et al. Outcomes of long-term treatment with laronidase in patients with Mucopolysaccharidosis Type I. J Pediatr. 2016; 178:219-226.
  7. Lehman TJA, Miller Nicole, Norquist B, et al. Diagnosis of the mucopolysaccharidoses. Rheumatology. 2011; 50:V41-V46.
  8. Martins AM, Dualibi AP, Norato D, et al. Guidelines for the management of mucopolysaccharidosis type I. J Pediatr. 2009: 155(4 Suppl):S32-S46.
  9. Perez-Lopez J, Morales-Conejo M, Lopez-Rodríguez M, et al. Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age. A systematic review and meta-analysis. Mol Genet Metab. 2017; 121(2):138-149.
  10. Thomas JA, Beck M, Clarke JTR, Cox GF. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. Journal of Inherited Metabolic Disease. 2010; 33(4):421-427.
  11. Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics. 2007; 120(1):e37-e46.
  12. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004; 144(5):581-588.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Thoracic Society (ATS). 2002. ATS Statement: Guidelines for the six-minute walk test. Available at: https://www.thoracic.org/statements/resources/pfet/sixminute.pdf. Accessed on August 11, 2017.
  2. Aldurazyme [Product Information], BioMarin Pharmaceutical Inc., Novato, CA and Genzyme Corporation, Cambridge, MA.; April 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125058s220lbl.pdf. Accessed in August 11, 2017.
  3. Clarke LA. Mucopolysaccharidosis I. 2002 Oct 31 [Updated 2016 Feb 11]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1162/. Accessed on August 11, 2017.
  4. Jameson E, Jones S, Remmington T. Enzyme replacement therapy with laronidase (Aldurazyme®) for treating mucopolysaccharidosis type I. Cochrane Database Syst Rev. 2016;(4):CD009354.
  5. Laronidase. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated September 21, 2016. Available at: http://www.micromedexsolutions.com. Accessed on August 11, 2017.
  6. Laronidase (Aldurazyme) Monograph. Lexicorp® Online, American Hospital Formulary Service® (AHFS®) Online; Hudson, Ohio, Lexi-Corp., Inc. Last revised December 2013. Accessed on August 11, 2017.
  7. Ratko TA, Marbella A, Godfrey, Aronson N. Enzyme replacement therapies for lysosomal storage disease [Internet]. 2013. Agency for Healthcare Research and Quality (US): Rockville, MD. Available at https://www.ncbi.nlm.nih.gov/books/NBK117219/. Accessed on August 11, 2017.
  8. Wang RY, Bodamer OA, Watson MS, Wilcox WR; American College of Medical Genetics (ACMG) Work Group on Diagnostic Confirmation of Lysosomal Storage Diseases. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet Med. 2011; 13(5):457-484.
Websites for Additional Information
  1. National Institute of Neurological Disorders and Stroke (NINDS). National Institutes of Health. Mucopolysaccharidoses Information Page. Available at: http://www.ninds.nih.gov/disorders/mucopolysaccharidoses/mucopolysaccharidoses.htm. Accessed on August 11, 2017.
Index

Aldurazyme
Laronidase
MPS I
Mucopolysaccharidosis I

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording updated from “Current Effective Date” to “Publish Date,” Minor punctuation change to Clinical Indications. Updated Discussion/General Information, Definitions, References, and Websites for Additional Information sections. 

New

11/03/2016

MPTAC review. Initial document development.